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Deng AQ, Yue SY, Niu D, Zhang DD, Hou BB, Zhang L, Liang CZ, Du HX. The role of microbiota in the chronic prostatitis/chronic pelvis pain syndrome: a review. Front Microbiol 2025; 16:1488732. [PMID: 40143861 PMCID: PMC11937130 DOI: 10.3389/fmicb.2025.1488732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Chronic prostatitis/Chronic pelvis pain syndrome (CP/CPPS), a kind of frequent urinary condition among adult males, has caused a lot of inconvenience to patients in life, whose pathogenesis is unclear. Current evidence suggests that it is most likely to be an autoimmune disease. Symbiotic microbes, a highly diverse biological community that harbors trillions of microbes in each region of the human body, have gradually made people realize their important role in immune regulation, material metabolism, and health maintenance. In recent years, increasing studies have shown a connection between microbiota and CP/CPPS. In view of this, we performed this review to summarize the literature pertaining to microbiota and its association with the pathophysiological mechanism of CP/CPPS. In addition, we gleaned the latest progress in the therapeutic strategy of CP/CPPS that related to microbiota regulation in order to offer new perspectives on the management of CP/CPPS.
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Affiliation(s)
- An-Qi Deng
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
- The Second Clinical Medical School, Anhui Medical University, Hefei, Anhui, China
| | - Shao-Yu Yue
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
| | - Di Niu
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
| | - Dan-Dan Zhang
- Clinical College of Anhui Medical University, Hefei, Anhui, China
| | - Bing-Bing Hou
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
| | - Li Zhang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
| | - Chao-Zhao Liang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
| | - He-Xi Du
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China
- Institute of Urology, Anhui Medical University, Hefei, Anhui, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, Anhui, China
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Süssmuth RD, Kulike-Koczula M, Gao P, Kosol S. Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research. Angew Chem Int Ed Engl 2025; 64:e202414325. [PMID: 39611429 DOI: 10.1002/anie.202414325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/15/2024] [Accepted: 10/15/2024] [Indexed: 11/30/2024]
Abstract
In the fight against bacterial infections, particularly those caused by multi-resistant pathogens known as "superbugs", the need for new antibacterials is undoubted in scientific communities and is by now also widely perceived by the general population. However, the antibacterial research landscape has changed considerably over the past years. With few exceptions, the majority of big pharma companies has left the field and thus, the decline in R&D on antibacterials severely impacts the drug pipeline. In recent years, antibacterial research has increasingly relied on smaller companies or academic research institutions, which mostly have only limited financial resources, to carry a drug discovery and development process from the beginning and through to the beginning of clinical phases. This review formulates the requirements for an antibacterial in regard of targeted pathogens, resistance mechanisms and drug discovery. Strategies are shown for the discovery of new antibacterial structures originating from natural sources, by chemical synthesis and more recently from artificial intelligence approaches. This is complemented by principles for the computer-aided design of antibacterials and the refinement of a lead structure. The second part of the article comprises a compilation of antibacterial molecules classified according to bacterial target structures, e.g. cell wall synthesis, protein synthesis, as well as more recently emerging target classes, e.g. fatty acid synthesis, proteases and membrane proteins. Aspects of the origin, the antibacterial spectrum, resistance and the current development status of the presented drug molecules are highlighted.
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Affiliation(s)
- Roderich D Süssmuth
- Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, TC2, 10629, Berlin, Germany
| | - Marcel Kulike-Koczula
- Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, TC2, 10629, Berlin, Germany
| | - Peng Gao
- Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, TC2, 10629, Berlin, Germany
| | - Simone Kosol
- Medical School Berlin, Department Human Medicine, Rüdesheimer Strasse 50, 14195, Berlin, Germany
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Szajewska H, Scott KP, de Meij T, Forslund-Startceva SK, Knight R, Koren O, Little P, Johnston BC, Łukasik J, Suez J, Tancredi DJ, Sanders ME. Antibiotic-perturbed microbiota and the role of probiotics. Nat Rev Gastroenterol Hepatol 2025; 22:155-172. [PMID: 39663462 DOI: 10.1038/s41575-024-01023-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/08/2024] [Indexed: 12/13/2024]
Abstract
The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a 'normal' microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research.
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Affiliation(s)
- Hania Szajewska
- Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
| | - Karen P Scott
- Rowett Institute, University of Aberdeen, Aberdeen, UK
| | - Tim de Meij
- Department of Paediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Academic Medical Centre, Amsterdam, The Netherlands
| | - Sofia K Forslund-Startceva
- Experimental and Clinical Research Center, a joint cooperation of Max Delbruck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, San Diego, CA, USA
- Department of Computer Science & Engineering, University of California San Diego, San Diego, CA, USA
- Shu Chien - Gene Lay Department of Bioengineering, University of California San Diego, San Diego, CA, USA
- Halıcıoğlu Data Science Institute, University of California San Diego, San Diego, CA, USA
- Center for Microbiome Innovation, University of California San Diego, San Diego, CA, USA
| | - Omry Koren
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Paul Little
- Primary Care Research Centre, University of Southampton, Southampton, UK
| | - Bradley C Johnston
- Department of Nutrition, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX, USA
- Department of Epidemiology and Biostatistics, School of Public Health, Texas A&M University, College Station, TX, USA
| | - Jan Łukasik
- Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
| | - Jotham Suez
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Daniel J Tancredi
- Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, CA, USA
| | - Mary Ellen Sanders
- International Scientific Association for Probiotics and Prebiotics, Consulting Scientific Advisor, Centennial, CO, USA.
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Chen Y, Li X, Sun X, Kou Y, Ma X, Song L, Zhang H, Xie F, Song Z, Yuan C, Huang S, Wu Y. Joint transcriptomics and metabolomics unveil the protective mechanism of tamarind seed polysaccharide against antibiotic-induced intestinal barrier damage. Int J Biol Macromol 2025; 305:140999. [PMID: 39952497 DOI: 10.1016/j.ijbiomac.2025.140999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 01/13/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
Intestinal barrier damage is frequently caused by antibiotic therapy, potentially leading to bacterial translocation and toxin leakage, which triggers inflammation and increases the risk of various diseases. In this study, Tamarind seed polysaccharides (TSP) with different molecular weights were administered to mice during the recovery phase from clindamycin-induced intestinal barrier damage. The results indicated that TSP restored the shortened colon length, reduced the enlarged cecum index, and decreased the elevated level of inflammatory infiltration. Biochemical testing revealed that TSP decreased the levels of intestinal permeability biomarkers and inflammatory factors that were elevated by clindamycin treatment. Transcriptomics and non-targeted metabolomics analyses respectively uncovered changes in colon gene expression and fecal metabolites. The joint analysis of these omics data identified critical pathways, including arachidonic acid metabolism, retinol metabolism, and steroid hormone biosynthesis. These findings suggest that TSP could be a promising dietary supplement for protecting the intestinal barrier and alleviating inflammation.
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Affiliation(s)
- Yinan Chen
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xujiao Li
- Institute for Agro-food Standards and Testing Technology, Laboratory of Quality & Safety Risk Assessment for Agro-products (Shanghai), Ministry of Agriculture and Rural Affairs, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China
| | - Xianbao Sun
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yuxing Kou
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xuan Ma
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Lihua Song
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hui Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Fan Xie
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Zibo Song
- Yunnan Maoduoli Group Food Co., Ltd., Yuxi 653100, China; Yunnan Special Favor Biotechnology Co., Ltd., Yuxi 653100, China
| | - Chunmei Yuan
- Yunnan Maoduoli Group Food Co., Ltd., Yuxi 653100, China; Yunnan Special Favor Biotechnology Co., Ltd., Yuxi 653100, China
| | - Siyan Huang
- Yunnan Maoduoli Group Food Co., Ltd., Yuxi 653100, China; Yunnan Special Favor Biotechnology Co., Ltd., Yuxi 653100, China
| | - Yan Wu
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
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Govender P, Ghai M. Population-specific differences in the human microbiome: Factors defining the diversity. Gene 2025; 933:148923. [PMID: 39244168 DOI: 10.1016/j.gene.2024.148923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/15/2024] [Accepted: 09/03/2024] [Indexed: 09/09/2024]
Abstract
Differences in microbial communities at different body habitats define the microbiome composition of the human body. The gut, oral, skin vaginal fluid and tissue microbiome, are pivotal for human development and immune response and cross talk between these microbiomes is evident. Population studies reveal that various factors, such as host genetics, diet, lifestyle, aging, and geographical location are strongly associated with population-specific microbiome differences. The present review discusses the factors that shape microbiome diversity in humans, and microbiome differences in African, Asian and Caucasian populations. Gut microbiome studies show that microbial species Bacteroides is commonly found in individuals living in Western countries (Caucasian populations), while Prevotella is prevalent in non-Western countries (African and Asian populations). This association is mainly due to the high carbohydrate, high fat diet in western countries in contrast to high fibre, low fat diets in African/ Asian regions. Majority of the microbiome studies focus on the bacteriome component; however, interesting findings reveal that increased bacteriophage richness, which makes up the virome component, correlates with decreased bacterial diversity, and causes microbiome dysbiosis. An increase of Caudovirales (bacteriophages) is associated with a decrease in enteric bacteria in inflammatory bowel diseases. Future microbiome studies should evaluate the interrelation between bacteriome and virome to fully understand their significance in the pathogenesis and progression of human diseases. With ethnic health disparities becoming increasingly apparent, studies need to emphasize on the association of population-specific microbiome differences and human diseases, to develop microbiome-based therapeutics. Additionally, targeted phage therapy is emerging as an attractive alternative to antibiotics for bacterial infections. With rapid rise in microbiome research, focus should be on standardizing protocols, advanced bioinformatics tools, and reducing sequencing platform related biases. Ultimately, integration of multi-omics data (genomics, transcriptomics, proteomics and metabolomics) will lead to precision models for personalized microbiome therapeutics advancement.
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Affiliation(s)
- Priyanka Govender
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, South Africa
| | - Meenu Ghai
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, South Africa.
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Kullberg RFJ, Haak BW, Chanderraj R, Prescott HC, Dickson RP, Wiersinga WJ. Empirical antibiotic therapy for sepsis: save the anaerobic microbiota. THE LANCET. RESPIRATORY MEDICINE 2025; 13:92-100. [PMID: 39401510 DOI: 10.1016/s2213-2600(24)00257-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 01/07/2025]
Abstract
Antibiotics are fundamental in sepsis management; however, the optimal empirical treatment remains debated. Despite anaerobes rarely being the causative pathogen of sepsis, antibiotics targeting them are frequently used, which might lead to unintended consequences. Multiple studies have shown that depletion of commensal anaerobic gut microbes by anti-anaerobic antibiotics influences systemic immunity and is associated with increased mortality in patients with sepsis. However, this knowledge has not yet been translated into clinical practice. When considering empirical coverage of anaerobic pathogens in sepsis, most physicians advocate for a better-safe-than-sorry approach. In this Viewpoint, we argue that anti-anaerobic antibiotics could often result in being sorry rather than safe. We provide an overview of the limited necessity of anaerobic coverage and the potential detrimental effects of anaerobic depletion in sepsis. We aim to raise anaerobic awareness to reduce the unnecessary use of anti-anaerobic antibiotics in empirical sepsis treatment and improve patient outcomes.
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Affiliation(s)
- Robert F J Kullberg
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
| | - Bastiaan W Haak
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Rishi Chanderraj
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Medicine Service, Infectious Diseases Section, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA; Weil Institute for Critical Care Research and Innovation, Ann Arbor, MI, USA
| | - Hallie C Prescott
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI, USA
| | - Robert P Dickson
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA; Weil Institute for Critical Care Research and Innovation, Ann Arbor, MI, USA
| | - W Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Division of Infectious Diseases, Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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7
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Kong X, Dong Z, Hu W, Mi J, Xiao J, Wang Y, Chen W, Pei Z, Hao Z, Liang C, Wang Q, Wang Z. The role of gut microbiota involved in prostate microenvironment and symptoms improvement in chronic prostatitis/chronic pelvic pain syndrome patients treated with low-intensity extracorporeal shock wave. Prostate 2024; 84:1525-1536. [PMID: 39308020 DOI: 10.1002/pros.24794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 08/08/2024] [Accepted: 08/29/2024] [Indexed: 11/14/2024]
Abstract
BACKGROUND Low-intensity extracorporeal shockwave therapy (Li-ESWT) is emerging as a promising and safe treatment for Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this study, we aimed to investigate the role of the gut microbiota involved in the prostate microenvironment and symptom improvement during the Li-ESWT for CP/CPPS patients. METHODS CP/CPPS patients not taking antibiotics or other treatments were included. NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5) were used to evaluate the effectiveness of Li-ESWT at the end of treatment. Visual analogue scale/score was used to evaluate the pain during procedure. Stool and semen samples were collected before and after Li-ESWT. Shotgun metagenomics analyzed gut microbiota, while ELISA and other diagnostic kits detected biochemical changes in seminal plasma. RESULT Of the 60 enrolled patients, 52 completed treatment. Li-ESWT response rate was 78.8% (41/52) at end of treatment. Among responders, the subitems of the NIH-CPSI; IPSS; and IIEF-5 scores improved significantly, and the seminal plasma analysis showed decreased TNF-a and MDA levels and increased SOD and Zn2+ levels posttreatment. Gut microbiome analysis indicated that posttreatment, both α and β diversity increased, and the abundance of certain specific species significantly increased. Fifty-eight pathways significantly enriched posttreatment, notably in branched-chain amino acid synthesis and butyrate synthesis. The abundance of several specific species was found to be significantly higher in non-responders than responders. Among responders, at the species level, some bacteria associated with NIH-CPSI and its subscales, IPSS, IIEF-5, and prostate microenvironment markers (TNF-a, MDA, Zn2+, and SOD) were identified. CONCLUSIONS Our study demonstrates for the first time that Li-ESWT improves the prostate microenvironment and gut microbiota in CP/CPPS patients. Treatment nonresponse may be associated with a high abundance of specific pathogens before treatment. The gut microbiota could have a significant impact on Li-ESWT response and the prostate microenvironment.
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Affiliation(s)
- Xiangbin Kong
- Department of Urology/Research Institute of Urology/Gansu Clinical Medical Research Center for Urological Diseases/Clinical Center of Gansu Province for Urological Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Zhilong Dong
- Department of Urology/Research Institute of Urology/Gansu Clinical Medical Research Center for Urological Diseases/Clinical Center of Gansu Province for Urological Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Weiwei Hu
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Jun Mi
- Department of Urology/Research Institute of Urology/Gansu Clinical Medical Research Center for Urological Diseases/Clinical Center of Gansu Province for Urological Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Jie Xiao
- The Second Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Yiran Wang
- Department of Urology/Research Institute of Urology/Gansu Clinical Medical Research Center for Urological Diseases/Clinical Center of Gansu Province for Urological Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Wenfang Chen
- The Second Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Zixu Pei
- The Second Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Zongyao Hao
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chaozhao Liang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qi Wang
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
| | - Zhiping Wang
- Department of Urology/Research Institute of Urology/Gansu Clinical Medical Research Center for Urological Diseases/Clinical Center of Gansu Province for Urological Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou City, Gansu Province, China
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Ali AQ, Sabir DK, Dawood AF, Abu-Rashed M, Hasari A, Gharqan F, Alnefaie S, Mohiddin LE, Tatry MM, Albadan DA, Alyami MM, Almutairi MF, Shawky LM. The potential liver injury induced by metronidazole-provoked disturbance of gut microbiota: modulatory effect of turmeric supplementation. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:9845-9858. [PMID: 38922353 DOI: 10.1007/s00210-024-03242-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024]
Abstract
It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130 mg/kg oral MNZ administration for 30 days. Meanwhile, the treatment group was orally treated with 100 mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.
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Affiliation(s)
- Abdulaziz Qaid Ali
- Vision Colleges, Riyadh, Saudi Arabia.
- Faculty of Medicine, University of Sciences and Technology, Sana'a, Yemen.
| | - Deema Kamal Sabir
- Department of Medical Surgical Nursing, College of Nursing, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia
| | - Amal F Dawood
- Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia
| | | | | | | | | | | | | | | | | | | | - Lamiaa M Shawky
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt
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9
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Li S, Zhang W, Liu S, Zhou Y, Liu W, Yuan W, He M. Effects of Tanreqing injection on the gut microbiota in healthy volunteers. Front Cell Infect Microbiol 2024; 14:1428476. [PMID: 39431053 PMCID: PMC11486765 DOI: 10.3389/fcimb.2024.1428476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 09/13/2024] [Indexed: 10/22/2024] Open
Abstract
Objectives Many studies have confirmed that antibacterial agents can disrupt the human gut microbiota. In China, Tanreqing injection (TRQ) is a drug with antibacterial activity that is widely used in the treatment of respiratory infections. However, its specific influence on gut microbiota remains unclear. This study aimed to investigate the effect of TRQ on the gut microbiota of healthy volunteers. Methods Twelve healthy adults received 20 ml of TRQ intravenously daily for 7 consecutive days. At six timepoints (Pre, on D1, D3, D5, D7 and follow-up visit) fecal samples were collected and analyzed using 16S rRNA gene sequencing. Results Eleven people were included in the analysis finally. TRQ did not significantly alter gut microbiota diversity or richness (Shannon and Simpson and Chao1 index) in healthy people during the intervention. Gut microbial structure was stable (weighted and unweighted Unifrac). Using a machine learning method based on PLS-DA analysis, the separation trend on D7 at the genus level was found, returning to baseline two days after discontinuation. The abundance of major genus fluctuated on D7 compared with that prior to treatment, including an increase of unclassified_f_Enterobacteriaceae (13.0611%), a decrease of Bifidobacterium and Escherichia-Shigella (6.887%, 10.487%). Functional prediction analysis did not reveal any significant difference. Conclusions Our study showed short-term use of TRQ at conventional doses may not cause perturbations to the gut microbiota in healthy adults. This finding provides some useful information for the safe use of TRQ in the treatment of respiratory infections. Clinical trial registration https://www.medicalresearch.org.cn/, identifier MR-31-24-014367.
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Affiliation(s)
- Shiyu Li
- Clinical Research Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenxia Zhang
- Department of Clinical Laboratory, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Sijie Liu
- Department of Pharmacy, The State Administration of Traditional Chinese Medicine (SATCM) Third Grade Laboratory of Traditional Chinese Medicine Preparations, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yichen Zhou
- Clinical Research Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Liu
- Department of Pharmacy, The State Administration of Traditional Chinese Medicine (SATCM) Third Grade Laboratory of Traditional Chinese Medicine Preparations, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Weian Yuan
- Clinical Research Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Min He
- Clinical Research Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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10
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Zeng SY, Liu YF, Zeng ZL, Zhao ZB, Yan XL, Zheng J, Chen WH, Wang ZX, Xie H, Liu JH. Antibiotic-induced gut microbiota disruption promotes vascular calcification by reducing short-chain fatty acid acetate. Mol Med 2024; 30:130. [PMID: 39182021 PMCID: PMC11344439 DOI: 10.1186/s10020-024-00900-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. METHODS Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. RESULTS ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. CONCLUSION ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.
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Affiliation(s)
- Shi-Yu Zeng
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Yi-Fu Liu
- The Second Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 330000, Jiangxi, China
| | - Zhao-Lin Zeng
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Zhi-Bo Zhao
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Xi-Lin Yan
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Jie Zheng
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Wen-Hang Chen
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zhen-Xing Wang
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China
| | - Hui Xie
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Jiang-Hua Liu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
- Hunan Diabetes Clinical Medical Research Center, Hengyang, 421001, Hunan, China.
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11
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Shang Z, Chen K, Han T, Bu F, Sun S, Zhu N, Man D, Yang K, Yuan S, Fu H. Natural Foraging Selection and Gut Microecology of Two Subterranean Rodents from the Eurasian Steppe in China. Animals (Basel) 2024; 14:2334. [PMID: 39199868 PMCID: PMC11350848 DOI: 10.3390/ani14162334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/30/2024] [Accepted: 08/08/2024] [Indexed: 09/01/2024] Open
Abstract
As the most abundant group of mammals, rodents possess a very rich ecotype, which makes them ideal for studying the relationship between diet and host gut microecology. Zokors are specialized herbivorous rodents adapted to living underground. Unlike more generalized herbivorous rodents, they feed on the underground parts of grassland plants. There are two species of the genus Myospalax in the Eurasian steppes in China: one is Myospalax psilurus, which inhabits meadow grasslands and forest edge areas, and the other is M. aspalax, which inhabits typical grassland areas. How are the dietary choices of the two species adapted to long-term subterranean life, and what is the relationship of this diet with gut microbes? Are there unique indicator genera for their gut microbial communities? Relevant factors, such as the ability of both species to degrade cellulose, are not yet clear. In this study, we analyzed the gut bacterial communities and diet compositions of two species of zokors using 16S amplicon technology combined with macro-barcoding technology. We found that the diversity of gut microbial bacterial communities in M. psilurus was significantly higher than that in M. aspalax, and that the two species of zokors possessed different gut bacterial indicator genera. Differences in the feeding habits of the two species of zokors stem from food composition rather than diversity. Based on the results of Mantel analyses, the gut bacterial community of M. aspalax showed a significant positive correlation with the creeping-rooted type food, and there was a complementary relationship between the axis root-type-food- and the rhizome-type-food-dominated (containing bulb types and tuberous root types) food groups. Functional prediction based on KEGG found that M. psilurus possessed a stronger degradation ability in the same cellulose degradation pathway. Neutral modeling results show that the gut flora of the M. psilurus has a wider ecological niche compared to that of the M. aspalax. This provides a new perspective for understanding how rodents living underground in grassland areas respond to changes in food conditions.
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Affiliation(s)
- Zhenghaoni Shang
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Kai Chen
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Tingting Han
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Fan Bu
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Shanshan Sun
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Na Zhu
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Duhu Man
- College of Agriculture, Hulunbuir University, Hulunbuir 021000, China;
| | - Ke Yang
- Alxa League Meteorological Bureau, Alxa 750300, China;
| | - Shuai Yuan
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
| | - Heping Fu
- College of Grassland Resources and Environment, Inner Mongolia Agricultural University, Hohhot 010011, China; (Z.S.); (K.C.); (T.H.); (F.B.); (S.S.); (N.Z.)
- Key Laboratory of Grassland Rodent Ecology and Pest Controlled, Hohhot 010011, China
- Key Laboratory of Grassland Resources, Ministry of Education, Hohhot 010011, China
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12
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Mann ER, Lam YK, Uhlig HH. Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol 2024; 24:577-595. [PMID: 38565643 DOI: 10.1038/s41577-024-01014-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2024] [Indexed: 04/04/2024]
Abstract
The short-chain fatty acids (SCFAs) butyrate, propionate and acetate are microbial metabolites and their availability in the gut and other organs is determined by environmental factors, such as diet and use of antibiotics, that shape the diversity and metabolism of the microbiota. SCFAs regulate epithelial barrier function as well as mucosal and systemic immunity via evolutionary conserved processes that involve G protein-coupled receptor signalling or histone deacetylase activity. Indicatively, the anti-inflammatory role of butyrate is mediated through direct effects on the differentiation of intestinal epithelial cells, phagocytes, B cells and plasma cells, and regulatory and effector T cells. Intestinally derived SCFAs also directly and indirectly affect immunity at extra-intestinal sites, such as the liver, the lungs, the reproductive tract and the brain, and have been implicated in a range of disorders, including infections, intestinal inflammation, autoimmunity, food allergies, asthma and responses to cancer therapies. An ecological understanding of microbial communities and their interrelated metabolic states, as well as the engineering of butyrogenic bacteria may support SCFA-focused interventions for the prevention and treatment of immune-mediated diseases.
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Affiliation(s)
- Elizabeth R Mann
- Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Ying Ka Lam
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Holm H Uhlig
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
- Department of Paediatrics, University of Oxford, Oxford, UK.
- Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
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13
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Taguer M, Xiao J, Crawford R, Shi H, Cheng MP, Citron M, Hannigan GD, Kasper SH. Spatial recovery of the murine gut microbiota after antibiotics perturbation. mBio 2024; 15:e0070724. [PMID: 38832780 PMCID: PMC11253616 DOI: 10.1128/mbio.00707-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 03/31/2024] [Indexed: 06/05/2024] Open
Abstract
Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of these microbial communities, yet studying the spatial organization of microbial communities at the single-cell level has been technically challenging. Here, we use the recently developed high-phylogenetic-resolution microbiota mapping by fluorescence in situ hybridization technology to image the gut microbiota at the species and single-cell level. We simultaneously image 63 different bacterial species to spatially characterize the perturbation and recovery of the gut microbiota to ampicillin and vancomycin in the cecum and distal colon of mice. To decipher the biology in this complex imaging data, we developed an analytical framework to characterize the spatial changes of the gut microbiota to a perturbation. The three-tiered analytical approach includes image-level diversity, pairwise colocalization analysis, and hypothesis-driven neighborhood analysis. Through this workflow, we identify biogeographic and antibiotic-based differences in the spatial organization of the gut microbiota. We demonstrate that the cecal microbiota has increased micrometer-scale diversity than the colon at baseline and recovers better from perturbation. Also, we identify potential foundation and keystone species that have high baseline neighborhood richness and that are associated with recovery from antibiotics. Through this workflow, we add a spatial layer to the characterization of bacterial communities and progress toward a better understanding of bacterial interactions leading to improved microbiome modulation strategies. IMPORTANCE Antibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.
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Affiliation(s)
- M. Taguer
- Discovery Immunology, MRL, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - J. Xiao
- Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, Pennsylvania, USA
| | - R. Crawford
- Informatics Technology, MRL, Merck & Co., Inc., West Point, Pennsylvania, USA
| | - H. Shi
- Kanvas Biosciences, Inc., Monmouth Junction, New Jersey, USA
| | - M. P. Cheng
- Kanvas Biosciences, Inc., Monmouth Junction, New Jersey, USA
| | - M. Citron
- Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, Pennsylvania, USA
| | - G. D. Hannigan
- Informatics Technology, MRL, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - S. H. Kasper
- Discovery Immunology, MRL, Merck & Co., Inc., Cambridge, Massachusetts, USA
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14
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Li X, Guo X, Liu Y, Ren F, Li S, Yang X, Liu J, Zhang Z. Antibiotics affect the pharmacokinetics of n-butylphthalide in vivo by altering the intestinal microbiota. PLoS One 2024; 19:e0297713. [PMID: 38917098 PMCID: PMC11198832 DOI: 10.1371/journal.pone.0297713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/31/2024] [Indexed: 06/27/2024] Open
Abstract
OBJECTIVE N-butylphthalide (NBP) is a monomeric compound extracted from natural plant celery seeds, whether intestinal microbiota alteration can modify its pharmacokinetics is still unclear. The purpose of this study is to investigate the effect of intestinal microbiota alteration on the pharmacokinetics of NBP and its related mechanisms. METHODS After treatment with antibiotics and probiotics, plasma NBP concentrations in SD rats were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The effect of intestinal microbiota changes on NBP pharmacokinetics was compared. Intestinal microbiota changes after NBP treatment were analyzed by 16S rRNA sequencing. Expressions of CYP3A1 mRNA and protein in the liver and small intestine tissues under different intestinal flora conditions were determined by qRT-PCR and Western Blot. KEGG analysis was used to analyze the effect of intestinal microbiota changes on metabolic pathways. RESULTS Compared to the control group, the values of Cmax, AUC0-8, AUC0-∞, t1/2 in the antibiotic group increased by 56.1% (P<0.001), 56.4% (P<0.001), 53.2% (P<0.001), and 24.4% (P<0.05), respectively. In contrast, the CL and Tmax values decreased by 57.1% (P<0.001) and 28.6% (P<0.05), respectively. Treatment with antibiotics could reduce the richness and diversity of the intestinal microbiota. CYP3A1 mRNA and protein expressions in the small intestine of the antibiotic group were 61.2% and 66.1% of those of the control group, respectively. CYP3A1 mRNA and protein expressions in the liver were 44.6% and 63.9% of those in the control group, respectively. There was no significant change in the probiotic group. KEGG analysis showed that multiple metabolic pathways were significantly down-regulated in the antibiotic group. Among them, the pathways of drug metabolism, bile acid biosynthesis and decomposition, and fatty acid synthesis and decomposition were related to NBP biological metabolism. CONCLUSION Antibiotic treatment could affect the intestinal microbiota, decrease CYP3A1 mRNA and protein expressions and increase NBP exposure in vivo by inhibiting pathways related to NBP metabolism.
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Affiliation(s)
- Xiangchen Li
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Xiaoli Guo
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Yixin Liu
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Feifei Ren
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Shan Li
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Xiuling Yang
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Jian Liu
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Zhiqing Zhang
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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15
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Wang Z, Guo Z, Liu L, Ren D, Zu H, Li B, Liu F. Potential Probiotic Weizmannia coagulans WC10 Improved Antibiotic-Associated Diarrhea in Mice by Regulating the Gut Microbiota and Metabolic Homeostasis. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10308-1. [PMID: 38900235 DOI: 10.1007/s12602-024-10308-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 06/21/2024]
Abstract
Antibiotic-associated diarrhea (AAD) is a common side effect of long-term and heavy antibiotic therapy. Weizmannia coagulans (W. coagulans) is an ideal probiotic because of its high viability, stability, and numerous health benefits to the host. In this study, the strains were first screened for W. coagulans WC10 (WC10) with a high combined ability based on their biological properties of gastrointestinal tolerance, adhesion, and short-chain fatty acid production ability. The effect of WC10 on mice with AAD was further evaluated. The results showed that WC10 was effective in improving the symptoms of AAD, effectively restoring antibiotic-induced weight loss, and reducing diarrhea status score and fecal water content. In addition, WC10 decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines, alleviated intestinal tissue damage and inflammation, and improved intestinal epithelial barrier function by decreasing serum levels of enterotoxin, DAO, and D-lactic acid, and by increasing the expression of the intestinal mucosal immune factors sIgA and occludin. Importantly, the composition and function of the gut microbiota gradually recovered after WC10 treatment, increasing the number of SCFAs-producing Bifidobacterium and Roseburia. Subsequently, the short-chain fatty acid (SCFA) content was examined and WC10 significantly increased acetate, propionate, and butyrate production. Additionally, metabolomic analysis also showed that WC10 reversed the antibiotic interference with major metabolic pathways. These findings provide a solid scientific basis for the future application of W. coagulans WC10 in the treatment of AAD.
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Affiliation(s)
- Zengbo Wang
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China
- Food College, Northeast Agricultural University, Harbin, 150030, China
| | - Zengtao Guo
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China
- Food College, Northeast Agricultural University, Harbin, 150030, China
| | - Libo Liu
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China
- Food College, Northeast Agricultural University, Harbin, 150030, China
| | - Daxi Ren
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Hang Zu
- Heilongjiang Ubert Dairy Co., Heilongjiang, China
| | - Bailiang Li
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
- Food College, Northeast Agricultural University, Harbin, 150030, China.
| | - Fei Liu
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
- Food College, Northeast Agricultural University, Harbin, 150030, China.
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16
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Seif El-Din MM, Hagras M, Mayhoub AS. Phenylthiazoles with potent & optimum selectivity toward Clostridium difficile. RSC Med Chem 2024; 15:1991-2001. [PMID: 38911156 PMCID: PMC11187570 DOI: 10.1039/d4md00164h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 03/21/2024] [Indexed: 06/25/2024] Open
Abstract
Clostridium difficile (C. difficile) is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires urgent and aggressive action. Interruption of the human gut microbiome and the development of antibiotic resistance urgently require development and synthesis of effective alternative antibiotics with minimal effects on the normal gut microbial flora. In this study, cyclization of the aminoguanidine head to the thiazole nucleus while maintaining its other pharmacophoric features leads to selective targeting of Clostridioides difficile as shown in the graphical abstract. The most promising compound, 5, was significantly more efficient than vancomycin and metronidazole against six strains of C. diff with MIC values as low as 0.030 μg mL-1. Additionally, compound 5 was superior to vancomycin and metronidazole, showing no inhibition toward nine tested strains of the normal human gut microbiota (>64 μg mL-1). The high safety profile of compound 5 was also observed with two cell lines HRT-18 and Vero cells.
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Affiliation(s)
- Mahmoud M Seif El-Din
- University of Science and Technology, Nanoscience Program, Zewail City of Science and Technology Ahmed Zewail Street Giza Egypt
| | - Mohamed Hagras
- Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University Cairo Egypt
| | - Abdelrahman S Mayhoub
- University of Science and Technology, Nanoscience Program, Zewail City of Science and Technology Ahmed Zewail Street Giza Egypt
- Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University Cairo Egypt
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17
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Kim R, Sung JH. Microfluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models. BIOMICROFLUIDICS 2024; 18:031507. [PMID: 38947281 PMCID: PMC11210976 DOI: 10.1063/5.0206271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 06/05/2024] [Indexed: 07/02/2024]
Abstract
The low success rate of new drugs transitioning from animal testing to human clinical trials necessitates the development of more accurate and representative in vitro models. Recent advances in multi-organ-on-a-chip technology offer promising avenues for studying complex organ-organ interactions. Gut-liver-on-a-chip systems hold particular promise for mimicking the intricate interplay between the gut and liver, which play crucial roles in nutrient absorption, drug metabolism, detoxification, and immune response. Here, we discuss the key components of the gut-liver axis, including the gut epithelium, liver cells, gut microbiota, and their roles in the organ functions. We then explore the potential of gut-liver-on-a-chip models to replicate the intricate interactions between the two organs for pharmacokinetic studies and their expansion to more complicated multi-organ models. Finally, we provide perspectives and future directions for developing more physiologically relevant gut-liver-axis models for more efficient drug development, studying liver diseases, and personalizing treatment strategies.
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Affiliation(s)
- Raehyun Kim
- Department of Biological and Chemical Engineering, Hongik University, Sejong 30016, Republic of Korea
| | - Jong Hwan Sung
- Department of Chemical Engineering, Hongik University, Seoul 04066, Republic of Korea
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18
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Sun M, Ju J, Xu H, Luo M, Li Z, Wang Y. Antibiotics influence the risk of anti-drug antibody formation during anti-TNF therapy in Chinese inflammatory bowel disease patients. Front Pharmacol 2024; 15:1360835. [PMID: 38655181 PMCID: PMC11035825 DOI: 10.3389/fphar.2024.1360835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 03/20/2024] [Indexed: 04/26/2024] Open
Abstract
Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD. Methods: A total of 166 patients with IBD, including 149 with Crohn's disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development. Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used β-lactam-β-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136-23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641-13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072-0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 μg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 μg/mL, p = 0.0121). Conclusion: ADA development is associated with various antibiotic classes. BL-BLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings.
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Affiliation(s)
| | | | | | | | | | - Yufang Wang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
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Catarci M, Guadagni S, Masedu F, Sartelli M, Montemurro LA, Baiocchi GL, Tebala GD, Borghi F, Marini P, Scatizzi M, The Italian ColoRectal Anastomotic Leakage iCral Study Group. Oral Antibiotics Alone versus Oral Antibiotics Combined with Mechanical Bowel Preparation for Elective Colorectal Surgery: A Propensity Score-Matching Re-Analysis of the iCral 2 and 3 Prospective Cohorts. Antibiotics (Basel) 2024; 13:235. [PMID: 38534670 DOI: 10.3390/antibiotics13030235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 02/27/2024] [Accepted: 03/01/2024] [Indexed: 03/28/2024] Open
Abstract
The evidence regarding the role of oral antibiotics alone (oA) or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8359 colorectal resections gathered over a 32-month period from 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA) and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infection (SSI) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs. 6 (2.5%) events; OR: 3.77; 95%CI: 1.22-11.67; p = 0.021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.
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Affiliation(s)
- Marco Catarci
- General Surgery Unit, Sandro Pertini Hospital, ASL Roma 2, 00157 Roma, Italy
| | - Stefano Guadagni
- General Surgery Unit, University of L'Aquila, 67100 L'Aquila, Italy
| | - Francesco Masedu
- Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, 67100 L'Aquila, Italy
| | - Massimo Sartelli
- General Surgery Unit, Santa Lucia Hospital, 62100 Macerata, Italy
| | | | - Gian Luca Baiocchi
- General Surgical Unit, Department of Clinical and Experimental Sciences, University of Brescia at the Azienda Socio Sanitaria Territoriale (ASST), 26100 Cremona, Italy
| | | | - Felice Borghi
- Oncologic Surgery Unit, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
| | - Pierluigi Marini
- General & Emergency Surgery Unit, San Camillo-Forlanini Hospital, 00152 Roma, Italy
| | - Marco Scatizzi
- General Surgery Unit, Santa Maria Annunziata & Serristori Hospital, 50012 Firenze, Italy
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20
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Bhardwaj G, Riadi Y, Afzal M, Bansal P, Kaur H, Deorari M, Tonk RK, Almalki WH, Kazmi I, Alzarea SI, Kukreti N, Thangavelu L, Saleem S. The hidden threat: Environmental toxins and their effects on gut microbiota. Pathol Res Pract 2024; 255:155173. [PMID: 38364649 DOI: 10.1016/j.prp.2024.155173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/23/2024] [Accepted: 01/24/2024] [Indexed: 02/18/2024]
Abstract
The human gut microbiota (GM), which consists of a complex and diverse ecosystem of bacteria, plays a vital role in overall wellness. However, the delicate balance of this intricate system is being compromised by the widespread presence of environmental toxins. The intricate connection between contaminants in the environment and human well-being has garnered significant attention in recent times. Although many environmental pollutants and their toxicity have been identified and studied in laboratory settings and animal models, there is insufficient data concerning their relevance to human physiology. Consequently, research on the toxicity of environmental toxins in GM has gained prominence in recent years. Various factors, such as air pollution, chemicals, heavy metals, and pesticides, have a detrimental impact on the composition and functioning of the GM. This comprehensive review aims to comprehend the toxic effects of numerous environmental pollutants, including antibiotics, endocrine-disrupting chemicals, heavy metals, and pesticides, on GM by examining recent research findings. The current analysis concludes that different types of environmental toxins can lead to GM dysbiosis and have various potential adverse effects on the well-being of animals. We investigate the alterations to the GM composition induced by contaminants and their impact on overall well-being, providing a fresh perspective on research related to pollutant exposure.
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Affiliation(s)
- Gautam Bhardwaj
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar sector-3, M-B Road, New Delhi 110017, India
| | - Yassine Riadi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Muhammad Afzal
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia
| | - Pooja Bansal
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Harpreet Kaur
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh 247341, India; Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand 831001, India
| | - Mahamedha Deorari
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Rajiv Kumar Tonk
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar sector-3, M-B Road, New Delhi 110017, India.
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341 Sakaka, Aljouf, Saudi Arabia
| | - Neelima Kukreti
- School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India
| | - Lakshmi Thangavelu
- Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
| | - Shakir Saleem
- Department of Public Health. College of Health Sciences, Saudi Electronic University, Riyadh, Saudi Arabia.
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21
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Niederhuber JE. The microbiome and cancer immunotherapy. CLINICAL IMMUNO-ONCOLOGY 2024:223-236.e4. [DOI: 10.1016/b978-0-323-87763-3.00020-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Alvarez-Zapata M, Franco-Vega A, Rondero AG, Guerra RS, Flores BIJ, Comas-García M, Ovalle CO, Schneider B, Ratering S, Schnell S, Martinez-Gutierrez F. Modulation of the Altered Intestinal Microbiota by Use of Antibiotics with a Novel Synbiotic on Wistar Rats. Probiotics Antimicrob Proteins 2023:10.1007/s12602-023-10204-0. [PMID: 38127241 DOI: 10.1007/s12602-023-10204-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2023] [Indexed: 12/23/2023]
Abstract
The use of antibiotics unbalances the intestinal microbiota. Probiotics, prebiotics, and synbiotics are alternatives for these unbalances. The effects of a new synbiotic composed of probiotic Saccharomyces boulardii CNCM I-745 and fructans from Agave salmiana (fAs) as prebiotics were assessed to modulate the intestinal microbiota. Two probiotic presentations, the commercial probiotic (CP) and the microencapsulated probiotic (MP) to improve those effects, were used to prepare the synbiotics and feed Wistar rats subjected to antibiotics (AB). Eight groups were studied, including five controls and three groups to modulate the microbiota after the use of antibiotics: G5: AB + MP-synbiotic, G6: AB + CP-synbiotic, and G8: AB + fAs. All treatments were administered daily for 7 days. On days 7 and 21, euthanasia was performed, cecum tissue was recovered and used to evaluate histological analysis and to study microphotograph by TEM, and finally, bacterial DNA was extracted and 16S rRNA gene metabarcode sequencing was performed. Histological analysis showed less epithelial damage and more abundance of the intestinal microbiota in the groups G5, G6, and G8 in comparison with the AB control group after 7 days. Microphotograph of the cecum at 2 weeks post treatment showed that G5 and G6 presented beneficial effects in epithelial reconstruction. Interestingly, in the groups that used the synbiotic without AB (G3 and G4) in addition to contributing to the recovery of the autochthonous microbiota, it promotes the development of beneficial microorganisms; those results were also achieved in the groups that used the synbiotic with AB enhancing the bacterial diversity and regulating the impact of AB.
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Affiliation(s)
- Miguel Alvarez-Zapata
- Laboratorio de Antimicrobianos, Biopelículas y Microbiota, Facultad de Ciencias Químicas, U.A.S.L.P., Av. Dr. Manuel Nava No. 6 Zona Universitaria, CP 78210, San Luis Potosí, S.L.P., México
| | - Avelina Franco-Vega
- Laboratorio de Tecnologías Emergentes, Facultad de Ciencias Químicas, U.A.S.L.P., San Luis Potosí, México
| | - Adriana Ganem Rondero
- Laboratorio de Investigación y Posgrado en Tecnología Farmacéutica (L-322), Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico City, Estado de México, México
| | - Ruth Soria Guerra
- Laboratorio de Biotecnología de plantas, Facultad de Ciencias Químicas, U.A.S.L.P., San Luis Potosí, México
| | | | - Mauricio Comas-García
- Sección de Genómica Médica, Centro de Investigación en Biomedicina y Salud, U.A.S.L.P., San Luis Potosí, México
- Sección de Microscopía de Alta Resolución, Centro de Investigación en Biomedicina y Salud, U.A.S.L.P., San Luis Potosí, Mexico
- Facultad de Ciencias, U.A.S.L.P., San Luis Potosi, Mexico
| | | | - Belinda Schneider
- Institute of Applied Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Stefan Ratering
- Institute of Applied Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Sylvia Schnell
- Institute of Applied Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Fidel Martinez-Gutierrez
- Laboratorio de Antimicrobianos, Biopelículas y Microbiota, Facultad de Ciencias Químicas, U.A.S.L.P., Av. Dr. Manuel Nava No. 6 Zona Universitaria, CP 78210, San Luis Potosí, S.L.P., México.
- Sección de Genómica Médica, Centro de Investigación en Biomedicina y Salud, U.A.S.L.P., San Luis Potosí, México.
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23
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Lin L, Zhang K, Xiong Q, Zhang J, Cai B, Huang Z, Yang B, Wei B, Chen J, Niu Q. Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression. J Autoimmun 2023; 141:103001. [PMID: 36931952 DOI: 10.1016/j.jaut.2023.103001] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 12/30/2022] [Accepted: 01/31/2023] [Indexed: 03/17/2023]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.
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Affiliation(s)
- Liyan Lin
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Keyi Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qiao Xiong
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Infection Control, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Junlong Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Cai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Zhuochun Huang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Yang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Wei
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
| | - Qian Niu
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
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24
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Cronin P, McCarthy S, Hurley C, Ghosh TS, Cooney JC, Tobin AM, Murphy M, O’Connor EM, Shanahan F, O’Toole PW. Comparative diet-gut microbiome analysis in Crohn's disease and Hidradenitis suppurativa. Front Microbiol 2023; 14:1289374. [PMID: 38029085 PMCID: PMC10667482 DOI: 10.3389/fmicb.2023.1289374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 10/27/2023] [Indexed: 12/01/2023] Open
Abstract
Introduction The chronic inflammatory skin disease Hidradenitis suppurativa (HS) is strongly associated with Crohn's Disease (CD). HS and CD share clinical similarities and similar inflammatory pathways are upregulated in both conditions. Increased prevalence of inflammatory disease in industrialised nations has been linked to the Western diet. However, gut microbiota composition and diet interaction have not been compared in HS and CD. Methods Here we compared the fecal microbiota (16S rRNA gene amplicon sequencing) and habitual diet of previously reported subjects with HS (n = 55), patients with CD (n = 102) and controls (n = 95). Results and discussion Patients with HS consumed a Western diet similar to patients with CD. Meanwhile, habitual diet in HS and CD was significantly different to controls. Previously, we detected differences in microbiota composition among patients with HS from that of controls. We now show that 40% of patients with HS had a microbiota configuration similar to that of CD, characterised by the enrichment of pathogenic genera (Enterococcus, Veillonella and Escherichia_Shigella) and the depletion of putatively beneficial genera (Faecalibacterium). The remaining 60% of patients with HS harboured a normal microbiota similar to that of controls. Antibiotics, which are commonly used to treat HS, were identified as a co-varying with differences in microbiota composition. We examined the levels of several inflammatory markers highlighting that growth-arrest specific 6 (Gas6), which has anti-inflammatory potential, were significantly lower in the 40% of patients with HS who had a CD microbiota configuration. Levels of the pro-inflammatory cytokine IL-12, which is a modulator of intestinal inflammation in CD, were negatively correlated with the abundance of health-associated genera in patients with HS. In conclusion, the fecal microbiota may help identify patients with HS who are at greater risk for development of CD.
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Affiliation(s)
- Peter Cronin
- Department of Biological Science, University of Limerick, Limerick, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Siobhan McCarthy
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Dermatology, South Infirmary Victoria University Hospital, Cork, Ireland
| | - Cian Hurley
- School of Microbiology, University College Cork, Cork, Ireland
| | - Tarini Shankar Ghosh
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Computational Biology, Indraprastha Institute of Information Technology Delhi (IIIT-Delhi), Delhi, India
| | - Jakki C. Cooney
- Department of Biological Science, University of Limerick, Limerick, Ireland
| | - Ann-Marie Tobin
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - Michelle Murphy
- Department of Dermatology, South Infirmary Victoria University Hospital, Cork, Ireland
- School of Medicine, University College Cork, Cork, Ireland
| | - Eibhlís M. O’Connor
- Department of Biological Science, University of Limerick, Limerick, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Health Research Institute, University of Limerick, Limerick, Ireland
| | - Fergus Shanahan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Medicine, University College Cork, Cork, Ireland
| | - Paul W. O’Toole
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
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25
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LeBlanc P, Ma L. Microbiome subcommunity learning with logistic-tree normal latent Dirichlet allocation. Biometrics 2023; 79:2321-2332. [PMID: 36222326 PMCID: PMC10090221 DOI: 10.1111/biom.13772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 09/26/2022] [Indexed: 11/28/2022]
Abstract
Mixed-membership (MM) models such as latent Dirichlet allocation (LDA) have been applied to microbiome compositional data to identify latent subcommunities of microbial species. These subcommunities are informative for understanding the biological interplay of microbes and for predicting health outcomes. However, microbiome compositions typically display substantial cross-sample heterogeneities in subcommunity compositions-that is, the variability in the proportions of microbes in shared subcommunities across samples-which is not accounted for in prior analyses. As a result, LDA can produce inference, which is highly sensitive to the specification of the number of subcommunities and often divides a single subcommunity into multiple artificial ones. To address this limitation, we incorporate the logistic-tree normal (LTN) model into LDA to form a new MM model. This model allows cross-sample variation in the composition of each subcommunity around some "centroid" composition that defines the subcommunity. Incorporation of auxiliary Pólya-Gamma variables enables a computationally efficient collapsed blocked Gibbs sampler to carry out Bayesian inference under this model. By accounting for such heterogeneity, our new model restores the robustness of the inference in the specification of the number of subcommunities and allows meaningful subcommunities to be identified.
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Affiliation(s)
- Patrick LeBlanc
- Department of Statistical Sciences, Duke University, Durham, North Carolina, USA
| | - Li Ma
- Department of Statistical Sciences, Duke University, Durham, North Carolina, USA
- Department of Biostatistics and Bioinformatics, Duke University Medical School, Durham, North Carolina, USA
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26
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Lyu Z, Hu Y, Guo Y, Liu D. Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis. Bone Res 2023; 11:31. [PMID: 37296111 PMCID: PMC10256815 DOI: 10.1038/s41413-023-00264-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 04/01/2023] [Accepted: 04/18/2023] [Indexed: 06/12/2023] Open
Abstract
The gut microbiota (GM) plays a crucial role in maintaining the overall health and well-being of the host. Recent studies have demonstrated that the GM may significantly influence bone metabolism and degenerative skeletal diseases, such as osteoporosis (OP). Interventions targeting GM modification, including probiotics or antibiotics, have been found to affect bone remodeling. This review provides a comprehensive summary of recent research on the role of GM in regulating bone remodeling and seeks to elucidate the regulatory mechanism from various perspectives, such as the interaction with the immune system, interplay with estrogen or parathyroid hormone (PTH), the impact of GM metabolites, and the effect of extracellular vesicles (EVs). Moreover, this review explores the potential of probiotics as a therapeutic approach for OP. The insights presented may contribute to the development of innovative GM-targeted therapies for OP.
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Affiliation(s)
- Zhengtian Lyu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Yongfei Hu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Yuming Guo
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Dan Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
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Wang J, Zhang X, Yang X, Yu H, Bu M, Fu J, Zhang Z, Xu H, Hu J, Lu J, Zhang H, Zhai Z, Yang W, Wu X, Wang Y, Tong Q. Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue. Front Cell Infect Microbiol 2023; 13:1191936. [PMID: 37260696 PMCID: PMC10229058 DOI: 10.3389/fcimb.2023.1191936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 04/24/2023] [Indexed: 06/02/2023] Open
Abstract
Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.
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Affiliation(s)
- Jingyue Wang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Xianfeng Zhang
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
| | - Xinyu Yang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Hang Yu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Mengmeng Bu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Jie Fu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Zhengwei Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Hui Xu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Jiachun Hu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Jinyue Lu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Haojian Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Zhao Zhai
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Wei Yang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Xiaodan Wu
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Yan Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
| | - Qian Tong
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
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28
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Chancharoenthana W, Kamolratanakul S, Schultz MJ, Leelahavanichkul A. The leaky gut and the gut microbiome in sepsis - targets in research and treatment. Clin Sci (Lond) 2023; 137:645-662. [PMID: 37083032 PMCID: PMC10133873 DOI: 10.1042/cs20220777] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 03/25/2023] [Accepted: 04/05/2023] [Indexed: 04/22/2023]
Abstract
Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1→3)-β-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.
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Affiliation(s)
- Wiwat Chancharoenthana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Tropical Immunology and Translational Research Unit (TITRU), Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Supitcha Kamolratanakul
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Tropical Immunology and Translational Research Unit (TITRU), Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Marcus J Schultz
- Department of Intensive Care and Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Asada Leelahavanichkul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand
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Karim MR, Iqbal S, Mohammad S, Lee JH, Jung D, Mathiyalagan R, Yang DC, Yang DU, Kang SC. A review on Impact of dietary interventions, drugs, and traditional herbal supplements on the gut microbiome. Microbiol Res 2023; 271:127346. [PMID: 36921399 DOI: 10.1016/j.micres.2023.127346] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/21/2023] [Accepted: 02/26/2023] [Indexed: 03/11/2023]
Abstract
The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.
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Affiliation(s)
- Md Rezaul Karim
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh; Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Safia Iqbal
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Department of Microbiology, Varendra Institute of Biosciences, Affiliated by Rajshahi University, Natore, Rajshahi, Bangladesh; Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Shahnawaz Mohammad
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Jung Hyeok Lee
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Daehyo Jung
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Ramya Mathiyalagan
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Deok-Chun Yang
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Dong Uk Yang
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
| | - Se Chan Kang
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea
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Thriene K, Michels KB. Human Gut Microbiota Plasticity throughout the Life Course. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1463. [PMID: 36674218 PMCID: PMC9860808 DOI: 10.3390/ijerph20021463] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 06/02/2023]
Abstract
The role of the gut microbiota in human health and disease has garnered heightened attention over the past decade. A thorough understanding of microbial variation over the life course and possible ways to influence and optimize the microbial pattern is essential to capitalize on the microbiota's potential to influence human health. Here, we review our current understanding of the concept of plasticity of the human gut microbiota throughout the life course. Characterization of the plasticity of the microbiota has emerged through recent research and suggests that the plasticity in the microbiota signature is largest at birth when the microbial colonization of the gut is initiated and mode of birth imprints its mark, then decreases postnatally continuously and becomes less malleable and largely stabilized with advancing age. This continuing loss of plasticity has important implication for the impact of the exposome on the microbiota and health throughout the life course and the identification of susceptible 'windows of opportunity' and methods for interventions.
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Affiliation(s)
- Kerstin Thriene
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, 79110 Freiburg, Germany
| | - Karin B. Michels
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, 79110 Freiburg, Germany
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA
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31
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Fernández-Alonso M, Aguirre Camorlinga A, Messiah SE, Marroquin E. Effect of adding probiotics to an antibiotic intervention on the human gut microbial diversity and composition: a systematic review. J Med Microbiol 2022; 71. [DOI: 10.1099/jmm.0.001625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Introduction. Millions of antibiotic prescriptions are written annually in the USA.
Gap Statement. Probiotics reduce antibiotic-induced gastrointestinal side effects; however, the effect of probiotics on preserving gut microbial composition in response to antibiotics is not well understood.
Aim. To evaluate whether the addition of probiotics is capable of reverting the changes in alpha diversity and gut microbial composition commonly observed in adult participants receiving antibiotics.
Methodology. A search was conducted by two researchers following the PRISMA guidelines using PubMed, Science Direct, Cochrane and Embase from January to December 2021 with the following inclusion criteria: (i) randomized clinical trials assessing the effect of antibiotics, probiotics or antibiotics+probiotics; (ii) 16S rRNA; (iii) adult participants; and (iv) in English. Once data was extracted in tables, a third researcher compared, evaluated and merged the collected data. The National Institutes of Health (NIH) rating system was utilized to analyse risk of bias.
Results. A total of 29 articles (n=11 antibiotics, n=11 probiotics and n=7 antibiotics+probiotics) met the inclusion criteria. The lack of standardization of protocols to analyse the gut microbial composition and the wide range of selected antibiotics/probiotics complicated data interpretation; however, despite these discrepancies, probiotic co-administration with antibiotics seemed to prevent some, but not all, of the gut microbial diversity and composition changes induced by antibiotics, including restoration of health-related bacteria such as
Faecalibacterium prausnitzii
.
Conclusion. Addition of probiotics to antibiotic interventions seems to preserve alpha diversity and ameliorate the changes to gut microbial composition caused by antibiotic interventions.
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Affiliation(s)
- Melissa Fernández-Alonso
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
| | | | - Sarah E. Messiah
- Center for Pediatric Population Health, UTHealth School of Public Health and Children's Health System of Texas, Dallas, TX, USA
- School of Public Health, University of Texas Health Science Center at Houston, Dallas Campus, Dallas, TX, USA
| | - Elisa Marroquin
- Department of Nutritional Sciences, College of Science and Engineering, Texas Christian University, Fort Worth, TX, USA
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Zhao Y, Zhou R, Guo Y, Chen X, Zhang A, Wang J, Ji F, Qin B, Geng J, Kong G, Li Z. Improvement of gut microbiome and intestinal permeability following splenectomy plus pericardial devascularization in hepatitis B virus-related cirrhotic portal hypertension. Front Immunol 2022; 13:941830. [PMID: 36159870 PMCID: PMC9493484 DOI: 10.3389/fimmu.2022.941830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022] Open
Abstract
The gut microbiome is an essential component of the intestinal mucosal barrier, critical in regulating intestinal permeability. Microbiome dysbiosis and intestinal permeability changes are commonly encountered conditions in patients with cirrhosis and are closely related to its development and further complications. However, alterations in the gut microbiome and intestinal permeability in chronic hepatitis B virus (HBV) patients with cirrhotic portal hypertension after undergoing a splenectomy plus pericardial devascularization (SPD) have not been investigated. This study recruited 22 patients who were measured against themselves on the study parameters before and after an SPD, along with 20 healthy controls. Methodologically, fecal samples were collected for gut microbiome analysis by 16S ribosomal DNA sequencing, and peripheral blood samples were obtained to examine the liver function and intestinal permeability. This study showed that the community structure of the gut microbiomes in patients before the SPD exhibited obvious differences from those in the healthy control group. They also exhibited a decreased bacterial community richness, increased intestinal permeability, and enhanced inflammation compared with the healthy controls. These issues were further aggravated two weeks after the SPD. There was also evidence of significantly higher abundances of Streptococcaceae, Enterobacteriaceae, and Enterococcaceae than those in the healthy control group. However, 12 months after the surgery, 12 of the 16 patient-associated genera recovered, of which 10 reached normal levels. Additionally, the microbiome diversity increased; the bacterial composition was back to a level similar to the healthy controls. Liver function, intestinal permeability, and inflammation levels all improved compared with preoperative levels. Furthermore, correlation analyses indicated that the five recovered bacterial taxa and the Shannon diversity index were correlated with several improved clinical indicators. Altogether, the improvements in the liver function and intestinal permeability in HBV-related cirrhotic patients may be related to the restoration of the gut microbiome after an SPD.
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Affiliation(s)
- Yang Zhao
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Rui Zhou
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ying Guo
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xi Chen
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Aiyu Zhang
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jiayin Wang
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, China
| | - Fanpu Ji
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Bowen Qin
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jing Geng
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Guangyao Kong
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Zongfang Li,
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Zhu W, Fu L, Xu C, Peng K, Liu Y, Tang H, Huang Y, Yang X. Enoxacin ameliorates polycystic ovary syndrome by promoting the browning of white adipose tissue and restoring gut dysbiosis. Front Pharmacol 2022; 13:978019. [PMID: 36147348 PMCID: PMC9486322 DOI: 10.3389/fphar.2022.978019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 08/15/2022] [Indexed: 12/02/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder syndrome characterized by polycystic ovary, ovulation disorder and hyperandrogenemia, and is often accompanied by metabolic disorders. Enoxacin has been reported to protect against diet-induced obesity and insulin resistance by promoting fat thermogenesis. However, the function of enoxacin in PCOS remains unknown. This study aimed to investigate the impact of the enoxacin on the regulation of PCOS mouse model induced by dehydroepiandrosterone (DHEA). Here, we found that reproductive endocrine disorder, glucose intolerance, and ovarian dysfunction in PCOS mice induced by DHEA were attenuated by enoxacin treatment. Mechanistically, we identified that enoxacin can promote white fat browning and improve metabolic disorders, thus ameliorating DHEA-induced reproductive dysfunction. Moreover, these beneficial effects might be associated with the restoration of gut dysbiosis. These findings provide a novel therapeutic target for enoxacin in the treatment of PCOS.
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Affiliation(s)
- Wanlong Zhu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Liya Fu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Changjing Xu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Ke Peng
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yuanzhi Liu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hui Tang
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yilan Huang
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Pharmacy, Southwest Medical University, Luzhou, China
- *Correspondence: Yilan Huang, ; Xuping Yang,
| | - Xuping Yang
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Pharmacy, Southwest Medical University, Luzhou, China
- *Correspondence: Yilan Huang, ; Xuping Yang,
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Malaeb H, Choucair I, Wang Z, Li XS, Li L, Boyd WC, Hine C, Tang WHW, Gogonea V, Hazen SL. Stable isotope dilution mass spectrometry quantification of hydrogen sulfide and thiols in biological matrices. Redox Biol 2022; 55:102401. [PMID: 35870340 PMCID: PMC9307673 DOI: 10.1016/j.redox.2022.102401] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Hydrogen sulfide (H2S), a gaseous signaling molecule that impacts multiple physiological processes including aging, is produced via select mammalian enzymes and enteric sulfur-reducing bacteria. H2S research is limited by the lack of an accurate internal standard-containing assay for its quantitation in biological matrices. METHODS After synthesizing [34S]H2S and developing sample preparation protocols that avoid sulfide contamination with the addition of thiol-containing standards or reducing reagents, we developed a stable isotope-dilution high performance liquid chromatography tandem-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Total H2S and other abundant thiols (cysteine, homocysteine, glutathione, glutamylcysteine, cysteinylglycine) in biological matrices, conducted a 20-day analytical validation/normal range study, and then both analyzed circulating Total H2S and thiols in plasma from 400 subjects, and within 20 volunteers before and after antibiotic-induced suppression of gut microbiota. RESULTS Using the new assay, all analytes showed minimal interference, no carryover, and excellent intra- and inter-day reproducibility (≤7.6%, and ≤12.7%, respectively), linearity (r2 > 0.997), recovery (90.9%-110%) and stability (90.0%-100.5%). Only circulating Total H2S levels showed significant age-associated reductions in both males and females (p < 0.001), and a marked reduction following gut microbiota suppression (mean 33.8 ± 17.7%, p < 0.001), with large variations in gut microbiota contribution among subjects (range 6.0-66.7% reduction with antibiotics). CONCLUSIONS A stable-isotope-dilution LC-MS/MS method is presented for the simultaneous quantification of Total H2S and multiple thiols in biological matrices. We then use this assay panel to show a striking age-related decline and gut microbiota contribution to circulating Total H2S levels in humans.
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Affiliation(s)
- Hind Malaeb
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Chemistry, Cleveland State University, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Ibrahim Choucair
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Zeneng Wang
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Xinmin S Li
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Lin Li
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | | | - Christopher Hine
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - W H Wilson Tang
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Valentin Gogonea
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Chemistry, Cleveland State University, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
| | - Stanley L Hazen
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Chemistry, Cleveland State University, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
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Impacts of Gut Microbiota on the Immune System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for Autoimmune Diseases. Antibiotics (Basel) 2022; 11:antibiotics11081093. [PMID: 36009962 PMCID: PMC9404867 DOI: 10.3390/antibiotics11081093] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/08/2022] [Accepted: 08/10/2022] [Indexed: 12/02/2022] Open
Abstract
The enormous and diverse population of microorganisms residing in the digestive tracts of humans and animals influence the development, regulation, and function of the immune system. Recently, the understanding of the association between autoimmune diseases and gut microbiota has been improved due to the innovation of high-throughput sequencing technologies with high resolutions. Several studies have reported perturbation of gut microbiota as one of the factors playing a role in the pathogenesis of many diseases, such as inflammatory bowel disease, recurrent diarrhea due to Clostridioides difficile infections. Restoration of healthy gut microbiota by transferring fecal material from a healthy donor to a sick recipient, called fecal microbiota transplantation (FMT), has resolved or improved symptoms of autoimmune diseases. This (re)emerging therapy was approved for the treatment of drug-resistant recurrent C. difficile infections in 2013 by the U.S. Food and Drug Administration. Numerous human and animal studies have demonstrated FMT has the potential as the next generation therapy to control autoimmune and other health problems. Alas, this new therapeutic method has limitations, including the risk of transferring antibiotic-resistant pathogens or transmission of genes from donors to recipients and/or exacerbating the conditions in some patients. Therefore, continued research is needed to elucidate the mechanisms by which gut microbiota is involved in the pathogenesis of autoimmune diseases and to improve the efficacy and optimize the preparation of FMT for different disease conditions, and to tailor FMT to meet the needs in both humans and animals. The prospect of FMT therapy includes shifting from the current practice of using the whole fecal materials to the more aesthetic transfer of selective microbial consortia assembled in vitro or using their metabolic products.
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Liakina V, Strainiene S, Stundiene I, Maksimaityte V, Kazenaite E. Gut microbiota contribution to hepatocellular carcinoma manifestation in non-alcoholic steatohepatitis. World J Hepatol 2022; 14:1277-1290. [PMID: 36158907 PMCID: PMC9376773 DOI: 10.4254/wjh.v14.i7.1277] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 04/27/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
Recently, the gut microbiota has been recognized as an obvious active player in addition to liver steatosis/steatohepatitis in the pathophysiological mechanisms of the development of hepatocellular carcinoma (HCC), even in the absence of cirrhosis. Evidence from clinical and experimental studies shows the association of specific changes in the gut microbiome and the direct contribution to maintaining liver inflammation and/or cancerogenesis in nonalcoholic fatty liver disease-induced HCC. The composition of the gut microbiota differs significantly in obese and lean individuals, especially in the abundance of pro-inflammatory lipopolysaccharide-producing phyla, and, after establishing steatohepatitis, it undergoes minor changes during the progression of the disease toward advanced fibrosis. Experimental studies proved that the microbiota of obese subjects can induce steatohepatitis in normally fed mice. On the contrary, the transplantation of healthy microbiota to obese mice relieves steatosis. However, further studies are needed to confirm these findings and the mechanisms involved. In this review, we have evaluated well-documented clinical and experimental research on the role of the gut microbiota in the manifestation and promotion of HCC in nonalcoholic steatohepatitis (NASH). Furthermore, a literature review of microbiota alterations and consequences of dysbiosis for the promotion of NASH-induced HCC was performed, and the advantages and limitations of the microbiota as an early marker of the diagnosis of HCC were discussed.
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Affiliation(s)
- Valentina Liakina
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, Vilnius Gediminas Technical University (VILNIUS TECH), Vilnius 10223, Lithuania
| | - Sandra Strainiene
- Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Therapeutic and Radiological Department, Antakalnis Polyclinic, Vilnius 10207, Lithuania
| | - Ieva Stundiene
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Vaidota Maksimaityte
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Edita Kazenaite
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
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Kumari R, Yadav Y, Misra R, Das U, Das Adhikari U, Malakar P, Dubey GP. Emerging frontiers of antibiotics use and their impacts on the human gut microbiome. Microbiol Res 2022; 263:127127. [PMID: 35914416 DOI: 10.1016/j.micres.2022.127127] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 04/17/2022] [Accepted: 07/11/2022] [Indexed: 02/07/2023]
Abstract
Antibiotics, the primary drugs used to cure bacterial diseases, are increasingly becoming ineffective due to the emergence of multiple drug resistance (MDR) leading to recurrence of previously sensitive pathogens. Human gut microbiome (GM), known to play an important role in various physiological processes, consists of pool of diverse microbes. Indiscriminate use of antibiotics during the life span of an individual may lead to development of resistant microbes e.g. Vibrio, Acinetobacter, Escherichia, Klebsiella, Clostridia, etc. in the human GM. Transmission of antibiotic resistant genes (ARGs) between pathogenic and commensal bacteria occurs more frequently in microbiome communities wherein bacteria communicate and exchange cellular constituents both among themselves and with the host. Additionally, co-factors like 'early vs. late' exposure, type of antibiotics and duration of treatment modulate the adverse effects of antibiotics on GM maturation. Furthermore, factors like mode of birth, ethnicity, malnutrition, demography, diet, lifestyle, etc., which influence GM composition, can also indirectly alter the host response to antibiotics. Currently, advanced 'omics' and culturomics approaches are revealing novel avenues to study the interplay between antibiotics and the microbiome and to identify resistant genes in these bacterial communities. Here, we discuss the recent developments that have given insights into the effects of antibiotics on the homeostatic balance of the gut microbiome and thus on human health.
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Affiliation(s)
- Rekha Kumari
- Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India.
| | - Yasha Yadav
- Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India
| | - Richa Misra
- Department of Zoology, Sri Venkateswara College, University of Delhi, Delhi 1100021, India
| | - Utpal Das
- Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Upasana Das Adhikari
- The Ragon Institute of MGH, MIT and Harvard, 400 Technology Square Cambridge, MA 02139, USA
| | - Pushkar Malakar
- Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Gyanendra P Dubey
- Molecular Microbial Pathogenesis Unit, Institut Pasteur, 28 rue du Docteur Roux, 75724 Cedex 15 Paris, France.
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Lindell AE, Zimmermann-Kogadeeva M, Patil KR. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat Rev Microbiol 2022; 20:431-443. [PMID: 35102308 PMCID: PMC7615390 DOI: 10.1038/s41579-022-00681-5] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2022] [Indexed: 02/08/2023]
Abstract
The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic-microbiota-host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.
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Affiliation(s)
- Anna E Lindell
- The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK
| | | | - Kiran R Patil
- The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK.
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Shute A, Bihan DG, Lewis IA, Nasser Y. Metabolomics: The Key to Unraveling the Role of the Microbiome in Visceral Pain Neurotransmission. Front Neurosci 2022; 16:917197. [PMID: 35812241 PMCID: PMC9260117 DOI: 10.3389/fnins.2022.917197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 05/30/2022] [Indexed: 11/29/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease and Ulcerative colitis, is a relapsing and remitting disease of the gastrointestinal tract, presenting with chronic inflammation, ulceration, gastrointestinal bleeding, and abdominal pain. Up to 80% of patients suffering from IBD experience acute pain, which dissipates when the underlying inflammation and tissue damage resolves. However, despite achieving endoscopic remission with no signs of ongoing intestinal inflammation or damage, 30-50% of IBD patients in remission experience chronic abdominal pain, suggesting altered sensory neuronal processing in this disorder. Furthermore, effective treatment for chronic pain is limited such that 5-25% of IBD outpatients are treated with narcotics, with associated morbidity and mortality. IBD patients commonly present with substantial alterations to the microbial community structure within the gastrointestinal tract, known as dysbiosis. The same is also true in irritable bowel syndrome (IBS), a chronic disorder characterized by altered bowel habits and abdominal pain, in the absence of inflammation. An emerging body of literature suggests that the gut microbiome plays an important role in visceral hypersensitivity. Specific microbial metabolites have an intimate relationship with host receptors that are highly expressed on host cell and neurons, suggesting that microbial metabolites play a key role in visceral hypersensitivity. In this review, we will discuss the techniques used to analysis the metabolome, current potential metabolite targets for visceral hypersensitivity, and discuss the current literature that evaluates the role of the post-inflammatory microbiota and metabolites in visceral hypersensitivity.
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Affiliation(s)
- Adam Shute
- Department of Medicine, Cumming School of Medicine, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Dominique G. Bihan
- Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
| | - Ian A. Lewis
- Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
| | - Yasmin Nasser
- Department of Medicine, Cumming School of Medicine, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
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Menard J, Goggs R, Mitchell P, Yang Y, Robbins S, Franklin-Guild RJ, Thachil AJ, Altier C, Anderson R, Putzel GG, McQueary H, Goodman LB. Effect of antimicrobial administration on fecal microbiota of critically ill dogs: dynamics of antimicrobial resistance over time. Anim Microbiome 2022; 4:36. [PMID: 35659110 PMCID: PMC9167539 DOI: 10.1186/s42523-022-00178-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 04/01/2022] [Indexed: 11/25/2022] Open
Abstract
Background Multidrug resistance in companion animals poses significant risks to animal and human health. Prolonged antimicrobial drug (AMD) treatment in animals is a potential source of selection pressure for antimicrobial resistance (AMR) including in the gastrointestinal microbiota. We performed a prospective study of dogs treated for septic peritonitis, pyometra, or bacterial pneumonia and collected repeated fecal samples over 60 days. Bacterial cultures and direct molecular analyses of fecal samples were performed including targeted resistance gene profiling. Results Resistant Escherichia coli increased after 1 week of treatment (D1:21.4% vs. D7:67.9% P < 0.001) and returned to baseline proportions by D60 (D7:67.9% vs D60:42.9%, P = 0.04). Dogs with septic peritonitis were hospitalized significantly longer than those with pneumonia or pyometra. Based on genetic analysis, Simpson’s diversity index significantly decreased after 1 week of treatment (D1 to D7, P = 0.008), followed by a gradual increase to day 60 (D1 and D60, P = 0.4). Detection of CTX-M was associated with phenotypic resistance to third-generation cephalosporins in E. coli (OR 12.1, 3.3–68.0, P < 0.001). Lincosamide and macrolide-resistance genes were more frequently recovered on days 14 and 28 compared to day 1 (P = 0.002 and P = 0.004 respectively). Conclusion AMR was associated with prescribed drugs but also developed against AMDs not administered during the study. Companion animals may be reservoirs of zoonotic multidrug resistant pathogens, suggesting that veterinary AMD stewardship and surveillance efforts should be prioritized. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s42523-022-00178-9.
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Affiliation(s)
- Julie Menard
- Department of Veterinary Diagnostic and Clinical Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
| | - Robert Goggs
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Patrick Mitchell
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Yufan Yang
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Sarah Robbins
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Rebecca J Franklin-Guild
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Anil J Thachil
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Craig Altier
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Renee Anderson
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Gregory G Putzel
- Microbiome Core Lab and Jill Roberts IBD Institute, Weill Cornell Medicine, Cornell University, New York City, NY, USA
| | - Holly McQueary
- Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Laura B Goodman
- Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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Van Engelen TSR, Yang J, Haak BW, Bonta PI, Van Der Poll T, Wiersinga WJ. Gut Microbiome Modulation by Antibiotics in Adult Asthma: A Human Proof-of-Concept Intervention Trial. Clin Gastroenterol Hepatol 2022; 20:1404-1407.e4. [PMID: 34303860 DOI: 10.1016/j.cgh.2021.07.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/15/2021] [Accepted: 07/19/2021] [Indexed: 02/07/2023]
Abstract
Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.1 Disruption and subsequent dysregulation of gut microbiota-related immunologic processes have also been linked to disease severity and response to treatment.2.
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Affiliation(s)
- Tjitske S R Van Engelen
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Jack Yang
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bastiaan W Haak
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Peter I Bonta
- Department of Respiratory Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Tom Van Der Poll
- Center for Experimental and Molecular Medicine, Department of Internal Medicine, Division of Infectious disease, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - W Joost Wiersinga
- Center for Experimental and Molecular Medicine, Department of Internal Medicine, Division of Infectious disease, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
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Dey P, Ray Chaudhuri S. Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches. BIOLOGY 2022; 11:757. [PMID: 35625485 PMCID: PMC9138768 DOI: 10.3390/biology11050757] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/08/2022] [Accepted: 05/12/2022] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.
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Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, India
| | - Saumya Ray Chaudhuri
- Council of Scientific and Industrial Research (CSIR), Institute of Microbial Technology, Chandigarh 160036, India;
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Moxifloxacin Induced Liver Injury by Causing Lachnospiraceae Deficiency and Interfering with Butyric Acid Production through Gut–Liver Axis. DISEASE MARKERS 2022; 2022:9302733. [PMID: 35531479 PMCID: PMC9076306 DOI: 10.1155/2022/9302733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 03/31/2022] [Indexed: 11/18/2022]
Abstract
Cases of unpredictable, idiosyncratic liver damage of moxifloxacin (MXF) have been occasionally reported. However, the health effects of MXF exposure remain controversial. The current study examined the metabolic phenotypes and intestinal flora characteristics of hepatotoxicity induced by MXF. Rats were administered moxifloxacin hydrochloride tablets at doses of 36, 72, and 108 mg/kg body weight/day for 21 days. The levels of tricarboxylic acid cycle intermediates were decreased, whereas those of lipids (arachidonic acid, hexadecanoic acid, and linoleic acid) were increased, reflecting disorders of energy–related and lipid metabolism. Enrichment analysis of the differential metabolites suggested that butanoate metabolism was associated with MXF–induced liver injury. 16S rRNA sequencing uncovered that the diversity of gut intestinal was decreased in MXF–treated rats. Specifically, the abundance of Muribaculaceae was increased, whereas that of Lachnospiraceae, a family of butyrate–producing bacteria, was decreased. The combined serum metabonomics and gut microbiome datasets illustrated the involvement of butanoic acid and energy metabolism in the regulatory changes of the gut–liver axis associated with MXF–induced liver injury. The regulation of endogenous small molecules and intestinal flora during drug–induced liver injury was first described from the perspective of the gut–liver axis, providing a research basis for the mechanism of clinical drug–induced liver injury.
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Lactobacillus casei Improve Anti-Tuberculosis Drugs-Induced Intestinal Adverse Reactions in Rat by Modulating Gut Microbiota and Short-Chain Fatty Acids. Nutrients 2022; 14:nu14081668. [PMID: 35458230 PMCID: PMC9032531 DOI: 10.3390/nu14081668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/05/2022] [Accepted: 04/14/2022] [Indexed: 02/07/2023] Open
Abstract
The adverse effects of anti-tuberculosis (TB) drugs in the intestines were related to alteration of the intestinal microbiota. However, there was less information about microbial metabolism on the adverse reactions. This study aimed to explore whether Lactobacillus casei could regulate gut microbiota or short-chain fatty acids (SCFAs) disorders to protect intestinal adverse reactions induced by isoniazid (H) and rifampicin (R). Male Wistar rats were given low and high doses of Lactobacillus casei two hours before daily administration of anti-TB drugs. After 42 days, colon tissue and blood were collected for analysis. The feces at two-week and six-week were collected to analyze the microbial composition and the content of SCFAs in colon contents was determined. Supplementation of Lactobacillus casei increased the proportion of intestinal goblet cells induced by H and R (p < 0.05). In addition, HR also reduced the level of mucin-2 (p < 0.05), and supplementation of Lactobacillus casei restored. After two weeks of HR intervention, a decrease in OTUs, diversity index, the abundance of Bacteroides, Akkermansia, and Blautia, and an increase of the abundance of Lacetospiraceae NK4A136 group and Rumencoccus UCG-005, were observed compared with the control group (p all < 0.05). These indices in Lactobacillus casei intervention groups were similar to the HR group. Six-week intervention resulted in a dramatic reduction of Lacetospiraceae NK4A136 group, butyric acid, valeric acid and hexanoic acid, while an increase of Bacteroides and Blautia (p all < 0.05). Pretreatment with Lactobacillus casei significantly increased the content of hexanoic acid compared with HR group (p < 0.05). Lactobacillus casei might prevent intestinal injury induced by anti-tuberculosis drugs by regulating gut microbiota and SCFAs metabolism.
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Mamieva Z, Poluektova E, Svistushkin V, Sobolev V, Shifrin O, Guarner F, Ivashkin V. Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations? World J Gastroenterol 2022; 28:1204-1219. [PMID: 35431513 PMCID: PMC8968486 DOI: 10.3748/wjg.v28.i12.1204] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/01/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.
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Affiliation(s)
- Zarina Mamieva
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Elena Poluektova
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Valery Svistushkin
- Department of Ear, Throat and Nose Diseases, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Vasily Sobolev
- Department of Ear, Throat and Nose Diseases, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Oleg Shifrin
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Francisco Guarner
- Digestive System Research Unit, Vall d’Hebron Research Institute, Barcelona 08035, Spain
| | - Vladimir Ivashkin
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
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Ternák G, Németh M, Rozanovic M, Bogár L. Alzheimer's Disease-Related Dysbiosis Might Be Triggered by Certain Classes of Antibiotics with Time-Lapse: New Insights into the Pathogenesis? J Alzheimers Dis 2022; 87:443-451. [PMID: 35275547 DOI: 10.3233/jad-220018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Several putative factors are identified in the literature as causative agents or risk factors for the development of Alzheimer's disease (AD). The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades, but recent studies raised the possible role of dysbiosis in the development of AD, which prevents memory loss. OBJECTIVE Finding possible associations between antibiotic consumption patterns and the prevalence of AD in European countries. METHODS Antibiotic consumption (European Centre for Disease Prevention and Control, ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, has been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. RESULTS A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the years 1997-2007 (r: 0.37, p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-2018, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (r: 0.406, p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (r: 0.344, p: 0.063), but none for the years 1997-2007 (r: 0.256, p: 0.241). CONCLUSION Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.
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Affiliation(s)
- Gábor Ternák
- University of Pécs, Medical School, Institute of Migration Health, Pécs, Hungary
| | - Márton Németh
- Department of Anesthesiology and Intensive Care, University of Pécs, Medical School, Pécs, Hungary
| | - Martin Rozanovic
- Department of Anesthesiology and Intensive Care, University of Pécs, Medical School, Pécs, Hungary
| | - Lajos Bogár
- Department of Anesthesiology and Intensive Care, University of Pécs, Medical School, Pécs, Hungary
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Lasting shift in the gut microbiota in patients with acute myeloid leukemia. Blood Adv 2022; 6:3451-3457. [PMID: 35192686 PMCID: PMC9198907 DOI: 10.1182/bloodadvances.2021006783] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/16/2022] [Indexed: 11/20/2022] Open
Abstract
The gut microbiota of patients with AML undergoes long-lasting changes during induction chemotherapy. Previous studies have shown that the gut microbiota of patients with acute myeloid leukemia (AML) is disrupted during induction chemotherapy; however, the durability of microbiota changes is unknown. This is an important knowledge gap, because reduced microbiota diversity at the time of stem cell transplantation weeks to months after the initial chemotherapy has been associated with higher mortality after transplantation. By sequencing the gut microbiota in 410 longitudinal stool samples from 52 patients with AML, we found that, during inpatient chemotherapy, the gut microbiota is stressed beyond its ability to recover its original state. Despite major reductions in antibiotic pressure and other disturbances to the microbiota after hospital discharge, the trajectory of microbiota recovery yields new communities that are highly dissimilar to baseline. This lasting shift in the gut microbiota is relevant for subsequent phases of curative therapy and is a potential target for novel microbiota protective/restorative interventions. This trial was registered at www.clinicaltrials.gov as #NCT03316456.
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Leopold SR, Abdelraouf K, Nicolau DP, Agresta H, Johnson J, Teter K, Dunne WM, Broadwell D, van Belkum A, Schechter LM, Sodergren EJ, Weinstock GM. Murine Model for Measuring Effects of Humanized-Dosing of Antibiotics on the Gut Microbiome. Front Microbiol 2022; 13:813849. [PMID: 35250930 PMCID: PMC8892246 DOI: 10.3389/fmicb.2022.813849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/13/2022] [Indexed: 11/29/2022] Open
Abstract
There is a current need for enhancing our insight in the effects of antimicrobial treatment on the composition of human microbiota. Also, the spontaneous restoration of the microbiota after antimicrobial treatment requires better understanding. This is best addressed in well-defined animal models. We here present a model in which immune-competent or neutropenic mice were administered piperacillin-tazobactam (TZP) according to human treatment schedules. Before, during and after the TZP treatment, fecal specimens were longitudinally collected at established intervals over several weeks. Gut microbial taxonomic distribution and abundance were assessed through culture and molecular means during all periods. Non-targeted metabolomics analyses of stool samples using Quadrupole Time of Flight mass spectrometry (QTOF MS) were also applied to determine if a metabolic fingerprint correlated with antibiotic use, immune status, and microbial abundance. TZP treatment led to a 5–10-fold decrease in bacterial fecal viability counts which were not fully restored during post-antibiotic follow up. Two distinct, relatively uniform and reproducible restoration scenarios of microbiota changes were seen in post TZP-treatment mice. Post-antibiotic flora could consist of predominantly Firmicutes or, alternatively, a more diverse mix of taxa. In general, the pre-treatment microbial communities were not fully restored within the screening periods applied. A new species, closely related to Eubacterium siraeum, Mageeibacillus indolicus, and Saccharofermentans acetigenes, became predominant post-treatment in a significant proportion of mice, identified by 16S rRNA gene sequencing. Principal component analysis of QTOF MS of mouse feces successfully distinguished treated from non-treated mice as well as immunocompetent from neutropenic mice. We observe dynamic but distinct and reproducible responses in the mouse gut microbiota during and after TZP treatment and propose the current murine model as a useful tool for defining the more general post-antibiotic effects in the gastro-intestinal ecosystem where humanized antibiotic dosing may ultimately facilitate extrapolation to humans.
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Affiliation(s)
- Shana R. Leopold
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Kamilia Abdelraouf
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States
| | - David P. Nicolau
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States
| | - Hanako Agresta
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Jethro Johnson
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Kathleen Teter
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | | | | | - Alex van Belkum
- BioMérieux SA, Clinical Unit, Grenoble, France
- *Correspondence: Alex van Belkum,
| | | | - Erica J. Sodergren
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
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Van Zyl KN, Matukane SR, Hamman BL, Whitelaw AC, Newton-Foot M. The effect of antibiotics on the human microbiome: a systematic review. Int J Antimicrob Agents 2021; 59:106502. [DOI: 10.1016/j.ijantimicag.2021.106502] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 12/01/2021] [Accepted: 12/11/2021] [Indexed: 12/01/2022]
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Ou WF, Wong LT, Wu CL, Chao WC. Culture positivity may correlate with long-term mortality in critically ill patients. BMC Infect Dis 2021; 21:1188. [PMID: 34836508 PMCID: PMC8620521 DOI: 10.1186/s12879-021-06898-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/23/2021] [Indexed: 11/10/2022] Open
Abstract
Background The long-term outcome is currently a crucial issue in critical care, and we aim to address the association between culture positivity and long-term mortality in critically ill patients. Methods We used the 2015–2019 critical care database at Taichung Veterans General Hospital and Taiwanese nationwide death registration files. Multivariable Cox proportional hazards regression model was conducted to determine hazard ratio (HR) and 95% confidence interval (CI). Results We enrolled 4488 critically ill patients, and the overall mortality was 55.2%. The follow-up duration among survivors was 2.2 ± 1.3 years. We found that 52.6% (2362/4488) of critically ill patients had at least one positive culture during the admission, and the number of patients with positive culture in the blood, respiratory tract and urinary tract were 593, 1831 and 831, respectively. We identified that a positive culture from blood (aHR 1.233; 95% CI 1.104–1.378), respiratory tract (aHR 1.217; 95% CI 1.109–1.364) and urinary tract (aHR 1.230; 95% CI 1.109–1.364) correlated with an increased risk of long-term mortality after adjusting relevant covariates. Conclusions Through linking two databases, we found that positive culture in the blood, respiratory tract and urinary tract during admission correlated with increased long-term overall mortality in critically ill patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06898-8.
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Affiliation(s)
- Wei-Fan Ou
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Li-Ting Wong
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chieh-Liang Wu
- Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung, 40705, Taiwan.,Department of Computer Science, Tunghai University, Taichung, Taiwan.,Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan.,Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan.,Artificial Intelligence Studio, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Cheng Chao
- Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung, 40705, Taiwan. .,Department of Computer Science, Tunghai University, Taichung, Taiwan. .,Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan. .,Big Data Center, Chung Hsing University, Taichung, Taiwan.
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