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Liu Z, Wang M, Li J, Liang Y, Jiang K, Hu Y, Gong W, Guo X, Guo Q, Zhu B. Hizikia fusiforme polysaccharides synergized with fecal microbiota transplantation to alleviate gut microbiota dysbiosis and intestinal inflammation. Int J Biol Macromol 2024; 283:137851. [PMID: 39566790 DOI: 10.1016/j.ijbiomac.2024.137851] [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: 06/21/2024] [Revised: 11/10/2024] [Accepted: 11/17/2024] [Indexed: 11/22/2024]
Abstract
Ulcerative colitis (UC) is closely associated with disruptions in gut microbiota. Restoring balance to gut microbiota and reducing intestinal inflammation has become a promising therapeutic approach for UC. However, challenges remain, including limited efficacy in some treatments. This study explores the synergistic effects and underlying mechanisms of Hizikia fusiforme polysaccharides (HFP) combined with fecal microbiota transplantation (FMT) to improve UC symptoms. Seven-week-old C57/BL6J mice were induced with UC using dextran sodium sulfate (DSS). Supplementation with either FMT alone or in combination with HFP effectively alleviated UC symptoms, reduced colonic inflammation, and corrected gut microbiota imbalance. Notably, HFP combined with FMT yielded showed better effects in ameliorating DSS-induced UC in mice than did FMT alone. Enrichment of probiotics, such as Bifidobacterium, and upregulation of beneficial metabolites, such as betaine, were identified as potential mechanisms for the enhanced effects of HFP combined with FMT against DSS-induced UC. These findings suggest that the combination of Hizikia fusiforme polysaccharides with FMT has potential applications in rectifying dysbiosis and ameliorating inflammatory bowel diseases.
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Affiliation(s)
- Zhengqi Liu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China; National Engineering Research Center of Seafood, National & Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China
| | - Menghui Wang
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Jinjin Li
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Yuxuan Liang
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Kaiyu Jiang
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Yuanyuan Hu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Wei Gong
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Xiaoming Guo
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China
| | - Qingbin Guo
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China; National Engineering Research Center of Seafood, National & Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China.
| | - Beiwei Zhu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, PR China; National Engineering Research Center of Seafood, National & Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China.
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Amrousy DE, Ashry HE, Maher S, Elsayed Y, Hasan S. Non-alcoholic fatty liver disease and the gut microbiota in adolescents: is there a relationship? BMC Pediatr 2024; 24:779. [PMID: 39609733 PMCID: PMC11606091 DOI: 10.1186/s12887-024-05268-y] [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: 08/09/2024] [Accepted: 11/21/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), the pathophysiology is still not fully understood. Recent evidence suggests that the gut microbiota may play a role in the pathophysiology of NAFLD and may also offer new therapeutic options. METHODS This prospective cross-sectional study included 100 consecutive newly diagnosed obese patients (BMI ≥ 95th percentile), aged 14-18 years with NAFLD (confirmed by ultrasound), persistently elevated levels of alanine aminotransferase (ALT) greater than 60 U/L for 1-6 months, and 100 healthy controls. We evaluated changes in the gut microbiota in NAFLD adolescents compared with healthy controls. RESULTS According to the multiple logistic regressions, the variables associated with NAFLD were the presence of Clostridium difficile, the presence of Salmonella spp., a greater abundance of Bifidobacterium and Prevotella, and a lower abundance of Lactobacillus. CONCLUSION Changes in the gut microbiota occur in adolescents with NAFLD compared with healthy individuals, which may be useful for identifying youths who are amenable to gut microbiota-based interventions. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Doaa El Amrousy
- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Heba El Ashry
- Tropical Medicine Departments, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Sara Maher
- Theodor Bilharz Research Institute, Cairo, Egypt.
- Immunology Lab, Theodor Bilharz Research Institute, Kornish El Nil Street, Giza, Egypt.
| | - Yousef Elsayed
- Kasr El Ainy Medical School, Cairo University, Cairo, Egypt
| | - Samir Hasan
- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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Zhang K, Nakaoka S. An energy landscape approach reveals the potential key bacteria contributing to the development of inflammatory bowel disease. PLoS One 2024; 19:e0302151. [PMID: 38885178 PMCID: PMC11182530 DOI: 10.1371/journal.pone.0302151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 03/28/2024] [Indexed: 06/20/2024] Open
Abstract
The dysbiosis of microbiota has been reported to be associated with numerous human pathophysiological processes, including inflammatory bowel disease (IBD). With advancements in high-throughput sequencing, various methods have been developed to study the alteration of microbiota in the development and progression of diseases. However, a suitable approach to assess the global stability of the microbiota in disease states through time-series microbiome data is yet to be established. In this study, we have introduced a novel Energy Landscape construction method, which incorporates the Latent Dirichlet Allocation (LDA) model and the pairwise Maximum Entropy (MaxEnt) model for their complementary advantages, and demonstrate its utility by applying it to an IBD time-series dataset. Through this approach, we obtained the microbial assemblages' energy profile of the whole microbiota under the IBD condition and uncovered the hidden stable stages of microbiota structure during the disease development with time-series microbiome data. The Bacteroides-dominated assemblages presenting in multiple stable states suggest the potential contribution of Bacteroides and interactions with other microbial genera, like Alistipes, and Faecalibacterium, to the development of IBD. Our proposed method provides a novel and insightful tool for understanding the alteration and stability of the microbiota under disease states and offers a more holistic view of the complex dynamics at play in microbiota-mediated diseases.
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Affiliation(s)
- Kaiyang Zhang
- Graduate School of Life Science, Hokkaido University, Sapporo, Japan
| | - Shinji Nakaoka
- Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan
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Chandel N, Maile A, Shrivastava S, Verma AK, Thakur V. Establishment and perturbation of human gut microbiome: common trends and variations between Indian and global populations. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2024; 5:e8. [PMID: 39776539 PMCID: PMC11704572 DOI: 10.1017/gmb.2024.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 01/11/2025]
Abstract
Human gut microbial species are crucial for dietary metabolism and biosynthesis of micronutrients. Digested products are utilised by the host as well as several gut bacterial species. These species are influenced by various factors such as diet, age, geographical location, and ethnicity. India is home to the largest human population in the world. It is spread across diverse ecological and geographical locations. With variable dietary habits and lifestyles, Indians have unique gut microbial composition. This review captures contrasting and common trends of gut bacterial community establishment in infants (born through different modes of delivery), and how that bacterial community manifests itself along infancy, through old age between Indian and global populations. Because dysbiosis of the gut community structure is associated with various diseases, this review also highlights the common and unique bacterial species associated with various communicable as well as noncommunicable diseases such as diarrhoea, amoebiasis, malnutrition, type 2 diabetes, obesity, colorectal cancer, inflammatory bowel disease, and gut inflammation and damage to the brain in the global and Indian population.
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Affiliation(s)
- Nisha Chandel
- Department of Systems and Computational Biology, University of Hyderabad, Hyderabad, India
| | - Anwesh Maile
- DBT-Centre for Microbial Informatics, University of Hyderabad, Hyderabad, India
| | - Suyesh Shrivastava
- ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, India
| | - Anil Kumar Verma
- ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, India
| | - Vivek Thakur
- Department of Systems and Computational Biology, University of Hyderabad, Hyderabad, India
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Guo J, Li L, Cai Y, Kang Y. The development of probiotics and prebiotics therapy to ulcerative colitis: a therapy that has gained considerable momentum. Cell Commun Signal 2024; 22:268. [PMID: 38745207 PMCID: PMC11094941 DOI: 10.1186/s12964-024-01611-z] [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: 10/10/2023] [Accepted: 04/10/2024] [Indexed: 05/16/2024] Open
Abstract
Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.
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Affiliation(s)
- Jing Guo
- Department of microbiology and immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Liping Li
- Department of microbiology and immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yue Cai
- Faculty of Life science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yongbo Kang
- Department of microbiology and immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China.
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Xu Y, Zhang H, Yang H, Liu C, Song C, Cheng Y, He C, Zou Z, Zhou D, Wu G, Zhang X. Eicosapentaenoic acid and docosahexaenoic acid suppress colonic tumorigenesis in obese mice. J Funct Foods 2024; 116:106164. [DOI: 10.1016/j.jff.2024.106164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
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Kennedy JM, De Silva A, Walton GE, Gibson GR. A review on the use of prebiotics in ulcerative colitis. Trends Microbiol 2024; 32:507-515. [PMID: 38065786 DOI: 10.1016/j.tim.2023.11.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 05/12/2024]
Abstract
The gut microbiome in the inflammatory bowel disease, ulcerative colitis (UC), is different to that of healthy controls. Patients with UC have relative reductions in abundance of Firmicutes and Bifidobacterium in the colon, and an increase in sulfate-reducing bacteria. Prebiotics are dietary substrates which are selectively metabolised by the human colonic microbiota to confer health benefits to the host. This review explores our current understanding of the potential benefits of prebiotics on various clinical, biochemical, and microbiological endpoints in UC, including new perspectives gained from recent studies in the field. This review looks to the future and highlights the need for appropriately designed trials to explore this potentially exciting new avenue for the treatment of UC.
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Affiliation(s)
- James M Kennedy
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK; Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading, RG1 5AN, UK.
| | - Aminda De Silva
- Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading, RG1 5AN, UK
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK
| | - Glenn R Gibson
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK
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Becker HE, Kameli N, Rustichelli A, Heijnens BA, Stassen FR, Penders J, Jonkers DM. In vitro mucin degradation and paracellular permeability by fecal water from Crohn's disease patients. Future Microbiol 2024; 19:335-347. [PMID: 38470403 DOI: 10.2217/fmb-2022-0265] [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: 11/28/2022] [Accepted: 08/30/2023] [Indexed: 03/13/2024] Open
Abstract
Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn's disease (CD) patients on mucin degradation and epithelial barrier function. Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12 CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Results: In vitro FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78-87% (p < 0.001). MVs did not induce barrier alterations. Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.
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Affiliation(s)
- Heike Ef Becker
- Department of Gastroenterology/Hepatology, Division of Internal Medicine, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
- Department of Medical Microbiology, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Nader Kameli
- Department of Medical Microbiology, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
- Department of Medical Microbiology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | | | - Britt Am Heijnens
- Department of Gastroenterology/Hepatology, Division of Internal Medicine, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Frank Rm Stassen
- Department of Medical Microbiology, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - John Penders
- Department of Medical Microbiology, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
- Department of Medical Microbiology, Caphri School for Public Health & Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Daisy Mae Jonkers
- Department of Gastroenterology/Hepatology, Division of Internal Medicine, NUTRIM School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
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Li J, Huang G, Wang J, Wang S, Yu Y. Hydrogen Regulates Ulcerative Colitis by Affecting the Intestinal Redox Environment. J Inflamm Res 2024; 17:933-945. [PMID: 38370464 PMCID: PMC10871146 DOI: 10.2147/jir.s445152] [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: 10/18/2023] [Accepted: 01/23/2024] [Indexed: 02/20/2024] Open
Abstract
The redox balance in the intestine plays an important role in maintaining intestinal homeostasis, and it is closely related to the intestinal mucosal barrier, intestinal inflammation, and the gut microbiota. Current research on the treatment of ulcerative colitis has focused on immune disorders, excessive inflammation, and oxidative stress. However, an imbalance in intestinal redox reaction plays a particularly critical role. Hydrogen is produced by some anaerobic bacteria via hydrogenases in the intestine. Increasing evidence suggests that hydrogen, as an inert gas, is crucial for immunity, inflammation, and oxidative stress and plays a protective role in ulcerative colitis. Hydrogen maintains the redox state balance in the intestine in ulcerative colitis and reduces damage to intestinal epithelial cells by exerting its selective antioxidant ability. Hydrogen also regulates the intestinal flora, reduces the harmful effects of bacteria on the intestinal epithelial barrier, promotes the restoration of normal anaerobic bacteria in the intestines, and ultimately improves the integrity of the intestinal epithelial barrier. The present review focuses on the therapeutic mechanisms of hydrogen-targeting ulcerative colitis.
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Affiliation(s)
- Jiayi Li
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Gang Huang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Juexin Wang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Sui Wang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China
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Kennedy JM, De Silva A, Walton GE, Poveda C, Gibson GR. Comparison of prebiotic candidates in ulcerative colitis using an in vitro fermentation model. J Appl Microbiol 2024; 135:lxae034. [PMID: 38337173 DOI: 10.1093/jambio/lxae034] [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: 09/03/2023] [Revised: 01/25/2024] [Accepted: 02/08/2024] [Indexed: 02/12/2024]
Abstract
AIMS This study explored the effect of three different prebiotics, the human milk oligosaccharide 2'-fucosyllactose (2'-FL), an oligofructose-enriched inulin (fructo-oligosaccharide, or FOS), and a galacto-oligosaccaride (GOS) mixture, on the faecal microbiota from patients with ulcerative colitis (UC) using in vitro batch culture fermentation models. Changes in bacterial groups and short-chain fatty acid (SCFA) production were compared. METHODS AND RESULTS In vitro pH controlled batch culture fermentation was carried out over 48 h on samples from three healthy controls and three patients with active UC. Four vessels were run, one negative control and one for each of the prebiotic substrates. Bacterial enumeration was carried out using fluorescence in situ hybridization with flow cytometry. SCFA quantification was performed using gas chromatography mass spectrometry. All substrates had a positive effect on the gut microbiota and led to significant increases in total SCFA and propionate concentrations at 48 h. 2'-FL was the only substrate to significantly increase acetate and led to the greatest increase in total SCFA concentration at 48 h. 2'-FL best suppressed Desulfovibrio spp., a pathogen associated with UC. CONCLUSIONS 2'FL, FOS, and GOS all significantly improved the gut microbiota in this in vitro study and also led to increased SCFA.
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Affiliation(s)
- James M Kennedy
- Department of Food and Nutritional Sciences, The University of Reading, Reading RG6 6AP, United Kingdom
- Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading RG1 5AN, United Kingdom
| | - Aminda De Silva
- Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading RG1 5AN, United Kingdom
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, The University of Reading, Reading RG6 6AP, United Kingdom
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, The University of Reading, Reading RG6 6AP, United Kingdom
| | - Glenn R Gibson
- Department of Food and Nutritional Sciences, The University of Reading, Reading RG6 6AP, United Kingdom
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11
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Arora U, Kedia S, Ahuja V. The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest Res 2024; 22:44-64. [PMID: 37981746 PMCID: PMC10850701 DOI: 10.5217/ir.2023.00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/21/2023] Open
Abstract
Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Affiliation(s)
- Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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12
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Pandey H, Jain D, Tang DWT, Wong SH, Lal D. Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease. Intest Res 2024; 22:15-43. [PMID: 37935653 PMCID: PMC10850697 DOI: 10.5217/ir.2023.00080] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 11/09/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Affiliation(s)
| | | | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
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13
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Tie Y, Huang Y, Chen R, Li L, Chen M, Zhang S. Current insights on the roles of gut microbiota in inflammatory bowel disease-associated extra-intestinal manifestations: pathophysiology and therapeutic targets. Gut Microbes 2023; 15:2265028. [PMID: 37822139 PMCID: PMC10572083 DOI: 10.1080/19490976.2023.2265028] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/26/2023] [Indexed: 10/13/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal tract. In addition to digestive symptoms, patients with IBD may also develop extra-intestinal manifestations (EIMs), the etiology of which remains undefined. The gut microbiota has been reported to exert a critical role in the pathogenesis of IBD, with a similar pattern of gut dysbiosis observed between patients with IBD and those with EIMs. Therefore, it is hypothesized that the gut microbiota is also involved in the pathogenesis of EIMs. The potential mechanisms are presented in this review, including: 1) impaired gut barrier: dysbiosis induces pore formation in the intestinal epithelium, and activates pattern recognition receptors to promote local inflammation; 2) microbial translocation: intestinal pathogens, antigens, and toxins translocate via the impaired gut barrier into extra-intestinal sites; 3) molecular mimicry: certain microbial antigens share similar epitopes with self-antigens, inducing inflammatory responses targeting extra-intestinal tissues; 4) microbiota-related metabolites: dysbiosis results in the dysregulation of microbiota-related metabolites, which could modulate the differentiation of lymphocytes and cytokine production; 5) immunocytes and cytokines: immunocytes are over-activated and pro-inflammatory cytokines are excessively released. Additionally, we summarize microbiota-related therapies, including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation, to promote better clinical management of IBD-associated EIMs.
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Affiliation(s)
- Yizhe Tie
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongle Huang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Rirong Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Gore R, Mohsenipour M, Wood JL, Balasuriya GK, Hill-Yardin EL, Franks AE. Hyperimmune bovine colostrum containing lipopolysaccharide antibodies (IMM124-E) has a nondetrimental effect on gut microbial communities in unchallenged mice. Infect Immun 2023; 91:e0009723. [PMID: 37830823 PMCID: PMC10652967 DOI: 10.1128/iai.00097-23] [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: 03/08/2023] [Accepted: 08/21/2023] [Indexed: 10/14/2023] Open
Abstract
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea with the potential to cause long-term gastrointestinal (GI) dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on GI commensals in healthy individuals are unclear. Whether administration of a prophylactic preventative treatment for ETEC-induced diarrhea causes specific shifts in gut microbial populations in controlled environments is also unknown. Here, we studied the effects of a hyperimmune bovine colostrum (IMM-124E) used in the manufacture of Travelan (AUST L 106709) on GI bacteria in healthy C57BL/6 mice. Using next-generation sequencing, we aimed to test the onset and magnitude of potential changes to the mouse gut microbiome in response to the antidiarrheagenic hyperimmune bovine colostrum product, rich in immunoglobulins against select ETEC strains (Travelan, Immuron Ltd). We show that in mice administered colostrum containing lipopolysaccharide (LPS) antibodies, there was an increased abundance of potentially gut-beneficial bacteria, such as Akkermansia and Desulfovibrio, without disrupting the underlying ecology of the GI tract. Compared to controls, there was no difference in overall weight gain, body or cecal weights, or small intestine length following LPS antibody colostrum supplementation. Overall, dietary supplementation with colostrum containing LPS antibodies produced subtle alterations in the gut bacterial composition of mice. Primarily, Travelan LPS antibody treatment decreased the ratio of Firmicutes/Bacteroidetes in gut microbial populations in unchallenged healthy mice. Further studies are required to examine the effect of Travelan LPS antibody treatment to engineer the microbiome in a diseased state and during recovery.
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Affiliation(s)
- Rachele Gore
- Neurodevelopment in Health and Disease Research Program, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Victoria, Australia
| | - Mitra Mohsenipour
- Neurodevelopment in Health and Disease Research Program, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia
| | - Jennifer L. Wood
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Victoria, Australia
| | - Gayathri K. Balasuriya
- Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan
| | - Elisa L. Hill-Yardin
- Neurodevelopment in Health and Disease Research Program, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia
| | - Ashley E. Franks
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Victoria, Australia
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15
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Volmer JG, McRae H, Morrison M. The evolving role of methanogenic archaea in mammalian microbiomes. Front Microbiol 2023; 14:1268451. [PMID: 37727289 PMCID: PMC10506414 DOI: 10.3389/fmicb.2023.1268451] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 08/18/2023] [Indexed: 09/21/2023] Open
Abstract
Methanogenic archaea (methanogens) represent a diverse group of microorganisms that inhabit various environmental and host-associated microbiomes. These organisms play an essential role in global carbon cycling given their ability to produce methane, a potent greenhouse gas, as a by-product of their energy production. Recent advances in culture-independent and -dependent studies have highlighted an increased prevalence of methanogens in the host-associated microbiome of diverse animal species. Moreover, there is increasing evidence that methanogens, and/or the methane they produce, may play a substantial role in human health and disease. This review addresses the expanding host-range and the emerging view of host-specific adaptations in methanogen biology and ecology, and the implications for host health and disease.
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Affiliation(s)
- James G. Volmer
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Harley McRae
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
| | - Mark Morrison
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
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16
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Wang CM, Fernez MT, Woolston BM, Carrier RL. Native gastrointestinal mucus: Critical features and techniques for studying interactions with drugs, drug carriers, and bacteria. Adv Drug Deliv Rev 2023; 200:114966. [PMID: 37329985 PMCID: PMC11184232 DOI: 10.1016/j.addr.2023.114966] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/09/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
Gastrointestinal mucus plays essential roles in modulating interactions between intestinal lumen contents, including orally delivered drug carriers and the gut microbiome, and underlying epithelial and immune tissues and cells. This review is focused on the properties of and methods for studying native gastrointestinal mucus and its interactions with intestinal lumen contents, including drug delivery systems, drugs, and bacteria. The properties of gastrointestinal mucus important to consider in its analysis are first presented, followed by a discussion of different experimental setups used to study gastrointestinal mucus. Applications of native intestinal mucus are then described, including experimental methods used to study mucus as a barrier to drug delivery and interactions with intestinal lumen contents that impact barrier properties. Given the significance of the microbiota in health and disease, its impact on drug delivery and drug metabolism, and the use of probiotics and microbe-based delivery systems, analysis of interactions of bacteria with native intestinal mucus is then reviewed. Specifically, bacteria adhesion to, motility within, and degradation of mucus is discussed. Literature noted is focused largely on applications of native intestinal mucus models as opposed to isolated mucins or reconstituted mucin gels.
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Affiliation(s)
- Chia-Ming Wang
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - Matthew T Fernez
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Benjamin M Woolston
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Rebecca L Carrier
- Department of Bioengineering, Northeastern University, Boston, MA, USA; Department of Chemical Engineering, Northeastern University, Boston, MA, USA; Department of Biology, Northeastern University, Boston, MA, USA.
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17
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Palandurkar GS, Kumar S. Biofilm's Impact on Inflammatory Bowel Diseases. Cureus 2023; 15:e45510. [PMID: 37868553 PMCID: PMC10585119 DOI: 10.7759/cureus.45510] [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: 08/18/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
The colon has a large surface area covered with a thick mucus coating. Colon's biomass consists of about 1,012 colony-forming units per gram of feces and 500-1,000 distinct bacterial species. The term inflammatory bowel disease (IBD) indicates the collection of intestinal illnesses in which the digestive system (esophagus, large intestine, mouth, stomach, and small intestine) experiences persistent inflammation. IBD development is influenced by environmental (infections, stress, and nutrition) and genetic factors. The microbes present in gut microbiota help maintain intestinal homeostasis and support immune and epithelial cell growth, differentiation, as well as proliferation. It has been discovered that a variety of variables and microorganisms are crucial for the development of biofilms and mucosal colonization during IBD. An extracellular matrix formed by bacteria supports biofilm production in our digestive system and harms the host's immunological response. Irritable bowel syndrome (IBS) and IBD considerably affect human socioeconomic well-being and the standard of living. IBD is a serious public health issue, affecting millions of people across the globe. The gut microbiome may significantly influence IBS pathogenesis, even though few diagnostic and treatment options are available. As a result, current research focuses more on disrupting biofilm in IBD patients and stresses primarily on drugs that help improve the quality of life for human well-being. We evaluate studies on IBD and bacterial biofilm to add fresh insights into the existing state of knowledge of biofilm formation in IBD, incidence of IBD patients, molecular level of investigations, bacteria that are involved in the formation of biofilm, and present and down the line regimens and probiotics. Planning advanced ways to control and eradicate bacteria in biofilms should be the primary goal to add fresh insights into generating innovative diagnostic and alternative therapy options for IBD.
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Affiliation(s)
- Gopal S Palandurkar
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunil Kumar
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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18
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Li L, Jiang Y, Zhu Q, Liu D, Chang M, Wang Y, Xi R, Wang W. Hyaluronan with Different Molecular Weights Can Affect the Gut Microbiota and Pathogenetic Progression of Post-Intensive Care Syndrome Mice in Different Ways. Int J Mol Sci 2023; 24:ijms24119757. [PMID: 37298710 DOI: 10.3390/ijms24119757] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 05/25/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023] Open
Abstract
Post-intensive care syndrome (PICS) poses a serious threat to the health of intensive care unit (ICU) survivors, and effective treatment options are currently lacking. With increasing survival rates of ICU patients worldwide, there is a rising interest in developing methods to alleviate PICS symptoms. This study aimed to explore the potential of using Hyaluronan (HA) with different molecular weights as potential drugs for treating PICS in mice. Cecal ligation and puncture (CLP) were used to establish a PICS mice model, and high molecular weight HA (HMW-HA) or oligo-HA were used as therapeutic agents. Pathological and physiological changes of PICS mice in each group were monitored. 16S rRNA sequencing was performed to dissect gut microbiota discrepancies. The results showed that both molecular weights of HA could increase the survival rate of PICS mice at the experimental endpoint. Specifically, 1600 kDa-HA can alleviate PICS in a short time. In contrast, 3 kDa-HA treatment decreased PICS model survivability in the early stages of the experiment. Further, via 16S rRNA sequence analysis, we observed the changes in the gut microbiota in PICS mice, thereby impairing intestinal structure and increasing inflammation. Additionally, both types of HA can reverse this change. Moreover, compared to 1600 kDa-HA, 3 kDa-HA can significantly elevate the proportion of probiotics and reduce the abundance of pathogenic bacteria (Desulfovibrionaceae and Enterobacteriaceae). In conclusion, HA holds the advantage of being a potential therapeutic drug for PICS, but different molecular weights can lead to varying effects. Moreover, 1600 kDa-HA showed promise as a protective agent in PICS mice, and caution should be taken to its timing when considering using 3 kDa-HA.
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Affiliation(s)
- Lu Li
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Yuanyuan Jiang
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Qianqian Zhu
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Dawei Liu
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Mingkai Chang
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Yongzhe Wang
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Ruitong Xi
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
| | - Wenfei Wang
- Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, Harbin 150030, China
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19
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Kedia S, Ahuja V. Human gut microbiome: A primer for the clinician. JGH Open 2023; 7:337-350. [PMID: 37265934 PMCID: PMC10230107 DOI: 10.1002/jgh3.12902] [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: 08/28/2022] [Revised: 12/14/2022] [Accepted: 04/01/2023] [Indexed: 06/03/2023]
Abstract
The human host gets tremendously influenced by a genetically and phenotypically distinct and heterogeneous constellation of microbial species-the human microbiome-the gut being one of the most densely populated and characterized site for these organisms. Microbiome science has advanced rapidly, technically with respect to the analytical methods and biologically with respect to its mechanistic influence in health and disease states. A clinician conducting a microbiome study should be aware of the nuances related to microbiome research, especially with respect to the technical and biological factors that can influence the interpretation of research outcomes. Hence, this review is an attempt to detail these aspects of the human gut microbiome, with emphasis on its determinants in a healthy state.
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Affiliation(s)
- Saurabh Kedia
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Vineet Ahuja
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
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20
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Aziz S, Waqas M, Iqbal A, Halim SA, Abdellattif MH, Khan A, Al-Harrasi A. Structure-based identification of potential substrate antagonists for isethionate sulfite-lyase enzyme of Bilophila Wadsworthia: Towards novel therapeutic intervention to curb gut-associated illness. Int J Biol Macromol 2023; 240:124428. [PMID: 37062383 DOI: 10.1016/j.ijbiomac.2023.124428] [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: 02/28/2023] [Revised: 04/03/2023] [Accepted: 04/09/2023] [Indexed: 04/18/2023]
Abstract
Bilophila wadsworthia is one of the prominent sources of hydrogen sulfide (H2S) production in appendices, excessive levels of which can result in a weaker colonic mucus barrier, inflammatory bowel disease, and colorectal cancer. Isethionate sulfite-lyase (IslA) enzyme catalyzes H2S production by cleaving CS bond in isethionate, producing acetaldehyde and sulfite. In this study, we aimed to identify potential substrate antagonists for IsIA using a structure-based drug design. Initially, pharmacophore-based computational screening of the ZINC20 database yielded 66 hits that were subjected to molecular docking targeting the isethionate binding site of IsIA. Based on striking docking scores, nine compounds showed strong interaction with critical IsIA residues (Arg189, Gln193, Glu470, Cys468, and Arg678), drug-like features, appropriate adsorption, metabolism, excretion, and excretion profile with non-toxicity. Molecular dynamics simulations uncovered the significant impact of binding the compounds on protein conformational dynamics. Finally, binding free energies revealed substantial binding affinity (ranging from -35.23 to -53.88 kcal/mol) of compounds (ZINC913876497, ZINC913856647, ZINC914263733, ZINC914137795, ZINC915757996, ZINC914357083, ZINC913934833, ZINC9143362047, and ZINC913854740) for IsIA. The compounds proposed herein through a multi-faceted computational strategy can be experimentally validated as potential substrate antagonists of B. wadsworthia's IsIA for developing new medications to curb gut-associated illness in the future.
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Affiliation(s)
- Shahkaar Aziz
- Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan
| | - Muhammad Waqas
- Department of Biotechnology and Genetic Engineering, Hazara University, Mansehra, Pakistan; Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman
| | - Aqib Iqbal
- Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan; Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan, Pakistan.
| | - Sobia Ahsan Halim
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman
| | - Magda H Abdellattif
- Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Ajmal Khan
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman.
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman.
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21
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Impact Assessment of vB_KpnP_K1-ULIP33 Bacteriophage on the Human Gut Microbiota Using a Dynamic In Vitro Model. Viruses 2023; 15:v15030719. [PMID: 36992428 PMCID: PMC10057081 DOI: 10.3390/v15030719] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/02/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
New control methods are needed to counter antimicrobial resistances and the use of bacteriophages as an alternative treatment seems promising. To that end, the effect of the phage vB_KpnP_K1-ULIP33, whose host is the hypervirulent Klebsiella pneumoniae SA12 (ST23 and capsular type K1), was assessed on intestinal microbiota, using an in vitro model: the SHIME® system (Simulator of the Human Intestinal Microbial Ecosystem). After stabilization of the system, the phage was inoculated for 7 days and its persistence in the different colons was studied until its disappearance from the system. The concentration of short chain fatty acids in the colons showed good colonization of the bioreactors by the microbiota and no significant effect related to the phage treatment. Diversity (α and β), the relative abundance of bacteria, and qPCR analysis targeting different genera of interest showed no significant variation following phage administration. Even if further in vitro studies are needed to assess the efficacy of this phage against its bacterial host within the human intestinal ecosystem, the phage ULIP33 exerted no significant change on the global colonic microbiota.
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22
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Upadhyay KG, Desai DC, Ashavaid TF, Dherai AJ. Microbiome and metabolome in inflammatory bowel disease. J Gastroenterol Hepatol 2023; 38:34-43. [PMID: 36287112 DOI: 10.1111/jgh.16043] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 10/19/2022] [Accepted: 10/23/2022] [Indexed: 01/19/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease of unknown etiology, involving complex interactions between the gut microbiome and host immune response. The microbial dysbiosis is well documented in IBD and significantly influences the host metabolic pathways. Thus, a metabolomic fingerprint resulting from the influence of gut dysbiosis in IBD could aid in assessing the disease activity. PubMed, Medline, Science Direct, and Web of Science were searched for studies exploring the association between microbiome and metabolome in IBD patients in the last 5 years. Additionally, references of cited original articles and reviews were further assessed for relevant work. We provide a literature overview of the recent metabolomic studies performed on patients with IBD. The findings report alterations in the metabolite levels of these patients. We also discuss the gut dysbiosis observed in IBD and its influence on host metabolic pathways such as lipids, amino acids, short-chain fatty acids, and others. IBD, being a chronic idiopathic disease, requires routine monitoring. The available non-invasive markers have their limitations. The metabolite changes account for both dysbiosis and its influence on the host's immune response and metabolism. A metabolome approach would thus facilitate the identification of surrogate metabolite markers reflecting the disease activity.
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Affiliation(s)
- Khushboo G Upadhyay
- Department of Laboratory Medicine, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Devendra C Desai
- Department of Gastroenterology, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Tester F Ashavaid
- Department of Laboratory Medicine, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Alpa J Dherai
- Department of Laboratory Medicine, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
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23
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Misra R, Sarafian M, Pechlivanis A, Ding N, Miguens-Blanco J, McDonald J, Holmes E, Marchesi J, Arebi N. Ethnicity Associated Microbial and Metabonomic Profiling in Newly Diagnosed Ulcerative Colitis. Clin Exp Gastroenterol 2022; 15:199-212. [PMID: 36505887 PMCID: PMC9733448 DOI: 10.2147/ceg.s371965] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 11/07/2022] [Indexed: 12/11/2022] Open
Abstract
Introduction Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues. Methods Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy. Results We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p<0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile. Conclusion Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response.
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Affiliation(s)
- Ravi Misra
- Gastroenterology, St Mark’s Academic Institute, London, UK,Correspondence: Ravi Misra, St. Mark’s Academic Institute, Imperial College, St. Mark’s Hospital, Watford Road, London, United Kingdom, Tel +44 0208 235 4124, Email
| | - Magali Sarafian
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK
| | | | - Nik Ding
- St Vincent’s Hospital, Inflammatory Bowel Disease Unit, Melbourne, Australia
| | - Jesus Miguens-Blanco
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK
| | | | - Elaine Holmes
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK,Health Futures Institute, Murdoch and Edith Cowan Universities, Murdoch, Australia
| | - Julian Marchesi
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK,School of Biosciences, Cardiff University, Cardiff, UK,Centre for Gut Health, Imperial College, London, UK
| | - Naila Arebi
- Gastroenterology, St Mark’s Academic Institute, London, UK
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24
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D'Aloisio LD, Shetty V, Ballal M, Gibson DL. Following the Indian Immigrant: adoption of westernization results in a western gut microbiome and an increased risk of inflammatory bowel diseases. FEMS Microbiol Ecol 2022; 98:6825449. [PMID: 36370451 DOI: 10.1093/femsec/fiac133] [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: 08/29/2022] [Revised: 11/01/2022] [Accepted: 11/10/2022] [Indexed: 11/13/2022] Open
Abstract
Indians who migrate to westernized countries such as Canada, the USA, and the UK are at an increased risk of developing inflammatory bowel disease (IBD). While the underlying aetiology of IBD remains unclear, a gut microbiome, i.e. no longer symbiotic with its host, is a major player. Increasing IBD incidence in Indian immigrants may be due to the adoption of western practices that result in loss of tolerance of a symbiotic community in the gut and its underlying immune responses. However, little is known about the microbial changes in the Indian gut, including shifts in the microbiome when they migrate to westernized countries. In this Current Opinion, we discuss what is known about the Indian gut microbiome and how living in a westernized environment may be impeding what was once a symbiotic relationship with their gut microbiome and intestinal mucosae, which may be the driving factor in their increased risk of IBD.
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Affiliation(s)
- Leah D D'Aloisio
- Department of Biology, University of British Columbia- Okanagan Campus, V1V 1V7 Kelowna, Canada
| | - Vignesh Shetty
- Enteric Disease Division, Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, 576104 Manipal, India.,Department of Medicine, University of Cambridge, CB2 2QQ Cambridge, United Kingdom
| | - Mamatha Ballal
- Enteric Disease Division, Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, 576104 Manipal, India
| | - Deanna L Gibson
- Department of Biology, University of British Columbia- Okanagan Campus, V1V 1V7 Kelowna, Canada.,Department of Medicine, University of British Columbia- Okanagan Campus, V1V 1V7 Kelowna, Canada
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25
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Oey O, Liu YY, Sunjaya AF, Simadibrata DM, Khattak MA, Gray E. Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review. World J Clin Oncol 2022; 13:929-942. [PMID: 36483977 PMCID: PMC9724183 DOI: 10.5306/wjco.v13.i11.929] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 10/30/2022] [Accepted: 11/07/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis.
AIM To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.
METHODS The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com).
RESULTS Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, P < 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis (P < 0.01) whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis (P < 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results.
CONCLUSION This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.
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Affiliation(s)
- Oliver Oey
- Department of Medical Oncology, St John of God Midland Public and Private Hospital, Midland, Perth 6004, WA, Australia
- School of Medicine, University of Western Australia, Perth 6009, WA, Australia
| | - Yu-Yang Liu
- School of Medicine, University of Queensland, Brisbane 4072, QLD, Australia
| | | | | | - Muhammad Adnan Khattak
- Department of Medical Oncology, Fiona Stanley Hospital, Perth 6150, WA, Australia
- School of Medical Sciences, Edith Cowan University, Perth 6027, WA, Australia
- Centre for Precision Health, Edith Cowan University, Perth 6027, WA, Australia
| | - Elin Gray
- School of Medical Sciences, Edith Cowan University, Perth 6027, WA, Australia
- Centre for Precision Health, Edith Cowan University, Perth 6027, WA, Australia
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Stummer N, Weghuber D, Feichtinger RG, Huber S, Mayr JA, Kofler B, Neureiter D, Klieser E, Hochmann S, Lauth W, Schneider AM. Hydrogen Sulfide Metabolizing Enzymes in the Intestinal Mucosa in Pediatric and Adult Inflammatory Bowel Disease. Antioxidants (Basel) 2022; 11:2235. [PMID: 36421421 PMCID: PMC9686699 DOI: 10.3390/antiox11112235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 08/27/2023] Open
Abstract
Hydrogen sulfide (H2S) is a toxic gas that has important regulatory functions. In the colon, H2S can be produced and detoxified endogenously. Both too little and too much H2S exposure are associated with inflammatory bowel disease (IBD), a chronic intestinal disease mainly classified as Crohn's disease (CD) and ulcerative colitis (UC). As the pathogenesis of IBD remains elusive, this study's aim was to investigate potential differences in the expression of H2S-metabolizing enzymes in normal aging and IBD. Intestinal mucosal biopsies of 25 adults and 22 children with IBD along with those of 26 healthy controls were stained immunohistochemically for cystathionine-γ-lyase (CSE), 3-mercapto-sulfurtransferase (3-MST), ethylmalonic encephalopathy 1 protein (ETHE1), sulfide:quinone oxidoreductase (SQOR) and thiosulfate sulfurtransferase (TST). Expression levels were calculated by multiplication of the staining intensity and percentage of positively stained cells. Healthy adults showed an overall trend towards lower expression of H2S-metabolizing enzymes than healthy children. Adults with IBD also tended to have lower expression compared to controls. A similar trend was seen in the enzyme expression of children with IBD compared to controls. These results indicate an age-related decrease in the expression of H2S-metabolizing enzymes and a dysfunctional H2S metabolism in IBD, which was less pronounced in children.
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Affiliation(s)
- Nathalie Stummer
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Daniel Weghuber
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - René G. Feichtinger
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Sara Huber
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Johannes A. Mayr
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Barbara Kofler
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Daniel Neureiter
- Institute of Pathology, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Eckhard Klieser
- Institute of Pathology, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Sarah Hochmann
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Wanda Lauth
- Department of Mathematics, Paris Lodron University, 5020 Salzburg, Austria
| | - Anna M. Schneider
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
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Zhu S, Han M, Liu S, Fan L, Shi H, Li P. Composition and diverse differences of intestinal microbiota in ulcerative colitis patients. Front Cell Infect Microbiol 2022; 12:953962. [PMID: 36111238 PMCID: PMC9468541 DOI: 10.3389/fcimb.2022.953962] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To explore the composition of the intestinal microbiota in ulcerative colitis (UC) patients and to identify differences in the microbiota between patients with active disease and those in remission. Methods Between September 2020 and June 2021, we enrolled into our study, and collected stool samples from, patients with active UC or in remission and healthy control subjects. The diagnosis of UC was based on clinical, endoscopic, radiological, and histological findings. The composition of the intestinal microbiota was determined by sequencing of the 16S rRNA V3–V4 region and by bioinformatic methods. The functional composition of the intestinal microbiota was predicted using PICRUSt 2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software. Results We found that the intestinal flora was significantly less rich and diverse in UC patients than in healthy control subjects. Beta diversity analysis revealed notable differences in the intestinal flora compositions among the three groups, but there was no statistical difference in alpha diversity between UC patients with active disease and those in remission. At the phylum level, the relative abundances of Proteobacteria and Patescibacteria were significantly higher, and the relative abundances of Desulfobacterota and Verrucomicrobiota were lower, in UC patients with active disease than in the healthy control group. Higher levels of potential pathogens and lower levels of butyrate-producing bacteria were also detected in UC patients with active disease. Linear discriminant analysis Effect Size (LefSe) revealed that 71 bacterial taxa could serve as biomarkers, with 26 biomarkers at the genus level. In addition, network analysis showed that there was a positive correlation between Roseburia and Lachnospira. Functional predictions indicated that gene functions involving the metabolism of some substances, such as methane, lipopolysaccharide, geraniol, and ansamycins, were significantly different among the three groups. Conclusion The richness and diversity of the intestinal microbiota differed significantly among the three groups. Richness describes the state of being rich in number of intestinal bacteria, whereas diversity is the number of different species of intestinal bacteria. Different bacterial taxa could be used as biomarkers, expanding our understanding of the relationship between the intestinal microbiota microenvironment and UC in the future.
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Affiliation(s)
| | | | | | | | | | - Peng Li
- *Correspondence: Haiyun Shi, ; Peng Li,
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Zhang Y, Si X, Yang L, Wang H, Sun Y, Liu N. Association between intestinal microbiota and inflammatory bowel disease. Animal Model Exp Med 2022; 5:311-322. [PMID: 35808814 PMCID: PMC9434590 DOI: 10.1002/ame2.12255] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 05/21/2022] [Indexed: 12/15/2022] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has emerged as a global disease with high incidence, long duration, devastating clinical symptoms, and low curability (relapsing immune response and barrier function defects). Mounting studies have been performed to investigate its pathogenesis to provide an ever‐expanding arsenal of therapeutic options, while the precise etiology of IBD is not completely understood yet. Recent advances in high‐throughput sequencing methods and animal models have provided new insights into the association between intestinal microbiota and IBD. In general, dysbiosis characterized by an imbalanced microbiota has been widely recognized as a pathology of IBD. However, intestinal microbiota alterations represent the cause or result of IBD process remains unclear. Therefore, more evidences are needed to identify the precise role of intestinal microbiota in the pathogenesis of IBD. Herein, this review aims to outline the current knowledge of commonly used, chemically induced, and infectious mouse models, gut microbiota alteration and how it contributes to IBD, and dysregulated metabolite production links to IBD pathogenesis.
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Affiliation(s)
- Yunchang Zhang
- Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Xuemeng Si
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Ling Yang
- Department of Food and Bioengineering, Beijing Vocational College of Agriculture, Beijing, China
| | - Hui Wang
- Department of Food and Bioengineering, Beijing Vocational College of Agriculture, Beijing, China
| | - Ye Sun
- Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, China
| | - Ning Liu
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, China
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Li H, Che H, Xie J, Dong X, Song L, Xie W, Sun J. Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo. Int J Biol Macromol 2022; 195:67-74. [PMID: 34896151 DOI: 10.1016/j.ijbiomac.2021.11.189] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/17/2021] [Accepted: 11/27/2021] [Indexed: 02/06/2023]
Abstract
The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1β, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.
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Affiliation(s)
- Hongyan Li
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China; Shandong Provincial Key Laboratory of biochemical engineering, Shandong, Qingdao 266042, China.
| | - Hongxia Che
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China; Shandong Provincial Key Laboratory of biochemical engineering, Shandong, Qingdao 266042, China
| | - Jingwen Xie
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China
| | - Xiufang Dong
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China; Shandong Provincial Key Laboratory of biochemical engineering, Shandong, Qingdao 266042, China
| | - Lin Song
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China; Shandong Provincial Key Laboratory of biochemical engineering, Shandong, Qingdao 266042, China
| | - Wancui Xie
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Shandong, Qingdao 266042, China; Shandong Provincial Key Laboratory of biochemical engineering, Shandong, Qingdao 266042, China
| | - Jinyuan Sun
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China.
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30
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Long CX, Wu JQ, Tan ZJ. Intestinal microbiota disturbance affects the occurrence of African swine fever. Anim Biotechnol 2021:1-10. [PMID: 34874229 DOI: 10.1080/10495398.2021.2010089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Intestinal microbiota not only participates in the digestion and absorption of nutrients, but also plays an important role in regulating host metabolism and health. The current study aimed to explore the intestinal microbiota characteristics in pigs infected with African swine fever. Below the same term, fresh fecal samples of sick and healthy pigs were collected. Primers were designed and PCR was extracted based on the 16S rDNA gene of bacteria by Illumina NovaSeq sequencing platform. The results showed that the bacterial alpha diversity index of healthy pigs was significantly higher than that of sick pigs (p < 0.05). On the phylum taxa, dominant bacteria more than 98.5% in the two groups are composed of Firmicutes, Spirobacteria, and Bacteroides, of which the abundance of Firmicutes and Bacteroidetes decreased and Spiricobacteria increased extremely significant in sick pigs (p < 0.01). On the genus taxa, the relative abundance of Oscillospira, Streptococcus and Roseburia decreased significantly (p < 0.05). Most notably, Treponema performed excellently in distinguishing pigs infected with African swine fever with the abundance increased extremely significantly (p < 0.01). In conclusion, African swine fever could alter the abundance of dominant bacteria in pigs, and Treponema may be one of the important inducers for swine pathogenicity. HighlightsThe bacterial population composition in sick pigs and healthy pigs was basically similar, but the relative abundance of dominant bacteria was significantly difference.ASF could alter the abundance of dominant bacteria in pigs, and Treponema may be one of the important inducers for swine pathogenicity.These results will provide further evidence for the ASF infection in local pig farms and provide reference for their microecological control, which has important practical significance and social value for effective control of ASF, stability of pig production and guarantee of market supply.
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Affiliation(s)
- Cheng-Xing Long
- College of Mathematics and Finance, Hunan University of Humanities, Science and Technology, Loudi, China
| | - Jie-Qi Wu
- Loudi Fisheries Science Research Institute, Loudi, China
| | - Zhou-Jin Tan
- College of Medicine, Hunan University of Chinese Medicine, Changsha, China
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Sultan S, El-Mowafy M, Elgaml A, Ahmed TAE, Hassan H, Mottawea W. Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease. Front Physiol 2021; 12:715506. [PMID: 34646151 PMCID: PMC8502967 DOI: 10.3389/fphys.2021.715506] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/18/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasive E. coli and H2S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.
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Affiliation(s)
- Salma Sultan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Mohammed El-Mowafy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Abdelaziz Elgaml
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.,Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| | - Tamer A E Ahmed
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Hebatoallah Hassan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
| | - Walid Mottawea
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Dai ZF, Ma XY, Yang RL, Wang HC, Xu DD, Yang JN, Guo XB, Meng SS, Xu R, Li YX, Xu Y, Li K, Lin XH. Intestinal flora alterations in patients with ulcerative colitis and their association with inflammation. Exp Ther Med 2021; 22:1322. [PMID: 34630676 DOI: 10.3892/etm.2021.10757] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 03/17/2021] [Indexed: 12/13/2022] Open
Abstract
Ulcerative colitis (UC), which is a type of inflammatory bowel disease, is a chronic intestinal disorder of multifactorial etiology. Numerous studies have indicated an association between UC and intestinal bacteria. However, a limited number of studies regarding the expression of interleukin-17 (IL-17) and interleukin-23 (IL-23) in association with intestinal bacteria have been performed. The aim of the current study was to investigate the gut microbiota alterations in patients with UC, at a number of taxonomic levels, and their relationship with intestinal inflammation by analyzing the protein expression of IL-17 and IL-23. Specimens were collected from 10 healthy controls and 16 patients with UC. A histological examination was performed in colonic tissues, IL-17 and IL-23 protein expression was detected by immunohistochemistry, fecal samples were sequenced using 16S rDNA sequencing and bioinformatics analysis was performed. The UC group exhibited an increased histological score (P<0.01) and upregulated IL-17 and IL-23 expression (P<0.01). At the order level, the bacterial diversity of the UC group was decreased. β-diversity analyses, including principal component analysis, principal coordinate analysis and non-metric multidimensional scaling, demonstrated that the two groups of samples were separated into two taxonomic categories, as distinct variations were observed in the analysis of group differences (P=0.001). Regarding the differences in species composition between the groups, Enterococcus was indicated to be the species with the greatest difference in abundance compared with the healthy control group (P<0.01), followed by Lactobacillus (P<0.05), Escherichia-Shigella (P<0.05), Bifidobacterium and Bacteroides. In addition, the average optical density of IL-17 was positively correlated with the histological score (ρ=0.669; P=0.035), Enterococcus (r=0.843; P<0.001), Lactobacillus (r=0.737; P=0.001), Bifidobacterium (r=0.773; P<0.001) and Escherichia-Shigella (r=0.663; P=0.005), and the average optical density of IL-23 was positively correlated with the histological score (ρ=0.733; P=0.016), Enterococcus (r=0.771; P<0.001), Lactobacillus (r=0.566; P=0.022), Bifidobacterium (r=0.517; P=0.041) and Escherichia-Shigella (r=0.613; P=0.012). The results of the present study indicated that the intestinal microbiota of patients with UC differed from that of healthy controls at multiple taxonomic levels. The alterations of the intestinal microflora were closely associated with the degree of inflammation. The IL-23/IL-17 axis, as a key factor in the development of UC, maybe associated with the alterations of intestinal microflora. The interaction between intestinal microflora and the IL-23/IL-17 axis may serve an important role in the pathogenesis of UC.
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Affiliation(s)
- Zhi Feng Dai
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Xu Yuan Ma
- Department of Gastroenterology, People's Hospital of Xuchang, Xuchang, Henan 461000, P.R. China
| | - Rui Lin Yang
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Hui Chao Wang
- Department of Nephrology, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Dan Dan Xu
- Department of Dermatology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Jing Nan Yang
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Xiao Bing Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Shuang Shuang Meng
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Rui Xu
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Yu Xia Li
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Yao Xu
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Kun Li
- Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Xu Hong Lin
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
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Li XX, Chen SG, Yue GGL, Kwok HF, Lee JKM, Zheng T, Shaw PC, Simmonds MSJ, Lau CBS. Natural flavone tricin exerted anti-inflammatory activity in macrophage via NF-κB pathway and ameliorated acute colitis in mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 90:153625. [PMID: 34256329 DOI: 10.1016/j.phymed.2021.153625] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/30/2021] [Accepted: 06/11/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Ulcerative colitis is a subtype of inflammatory bowel disease, characterized by relapsing inflammation in the gastrointestinal tract with limited treatment options. Previous studies suggested that the natural compound tricin, a flavone isolated from rice bran, could suppress chemically-induced colitis in mice, while our recent study also demonstrated the anti-metastatic effect of tricin in colon tumor-bearing mice. HYPOTHESIS/PURPOSE Here we further investigated the underlying mechanism of the inhibitory effects of tricin on lipopolysaccharides-activated macrophage RAW264.7 cells and explored the efficacy of tricin in acute colitis mouse model induced by 4.5% dextran sulfate sodium (DSS) for 7 days. METHODS Tricin (75, 100, and 150 mg/kg) or the positive control drug sulfasalazine (200 mg/kg) were orally administered to mice for 7 days. Stool consistency scores, stool blood scores, and body weight were recorded daily. Disease activity index (DAI) was examined on day 7, and colon tissues were collected for biochemical analyses. The fecal microbiome of colitis mice after tricin treatment was characterized for the first time in this study using 16S rDNA amplicon sequencing. RESULTS Results showed that tricin (50 µM) remarkably reduced nitric oxide production in lipopolysaccharides-activated RAW264.7 cells and the anti-inflammatory activity of tricin was shown to act through the NF-κB pathway. Besides, tricin treatment at 150 mg/kg significantly reversed colon length reduction, reduced myeloperoxidase activities and DAI scores, as well as restored the elevated myeloid-derived suppressive cells population in acute colitis mice. The influence from DSS on gut microbiota, such as the increased population of Proteobacteria phylum and Ruminococcaceae family, was shown to be relieved after tricin treatment. CONCLUSION Our present study firstly demonstrated that tricin ameliorated acute colitis by improving colonic inflammation and modulating gut microbiota profile, which supports the potential therapeutic use of tricin for colitis treatment.
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Affiliation(s)
- Xiao-Xiao Li
- Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Sin-Guang Chen
- Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Grace Gar-Lee Yue
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Hin-Fai Kwok
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Julia Kin-Ming Lee
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Tao Zheng
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Pang-Chui Shaw
- Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | | | - Clara Bik-San Lau
- Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
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The Role of H 2S in the Gastrointestinal Tract and Microbiota. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1315:67-98. [PMID: 34302689 DOI: 10.1007/978-981-16-0991-6_4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The pathways and mechanisms of the production of H2S in the gastrointestinal tract are briefly described, including endogenous H2S produced by the organism and H2S from microorganisms in the gastrointestinal tract. In addition, the physiological regulatory functions of H2S on gastrointestinal motility, sensation, secretion and absorption, endocrine system, proliferation and differentiation of stem cells, and the possible mechanisms involved are introduced. In view of the complexity of biosynthesis, physiological roles, and the mechanism of H2S, this chapter focuses on the interactions and dynamic balance among H2S, gastrointestinal microorganisms, and the host. Finally, we focus on some clinical gastrointestinal diseases, such as inflammatory bowel disease, colorectal cancer, functional gastrointestinal disease, which might occur or develop when the above balance is broken. Pharmacological regulation of H2S or the intestinal microorganisms related to H2S might provide new therapeutic approaches for some gastrointestinal diseases.
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Abstract
Inflammatory bowel disease (IBD) in recent times is causing a significant healthcare burden as both ulcerative colitis and Crohn's disease (CD) require lifelong therapy and constant monitoring. The current review highlights the concerns in a country like India with special reference to the changing trends of IBD, risk attribution and the financial issues. Indian immigrants behave like residential Indians, whereas their children show IBD prevalence similar to the West, highlighting the role of environmental triggers. However, the environmental and genetic factors in Indians with IBD are not well understood. Men appear to be more frequently affected than women in India. The disease severity is milder in the patients, both males and females, but the risk for colorectal cancer (CRC) is similar to the West. The incidence of paediatric IBD is on the rise. The major burden of IBD in the Indian subcontinent at present is in children, adolescents and teens. Cost towards the management of complications, non-adherence to treatment, differentiating tuberculosis from CD and finally screening for CRC in patients with IBD are the points to ponder in the Indian scenario.
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Affiliation(s)
- Mayank Jain
- Department of Medical Gastroenterology, Gleneagles Global Health City, Chennai, India
| | - Jayanthi Venkataraman
- Department of Medical Gastroenterology, Gleneagles Global Health City, Chennai, India
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Yao Q, Li H, Fan L, Zhang Y, Zhao S, Zheng N, Wang J. Dietary Regulation of the Crosstalk between Gut Microbiome and Immune Response in Inflammatory Bowel Disease. Foods 2021; 10:foods10020368. [PMID: 33567698 PMCID: PMC7915342 DOI: 10.3390/foods10020368] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/01/2021] [Accepted: 02/03/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), a chronic, recurring inflammatory response, is a growing global public health issue. It results from the aberrant crosstalk among environmental factors, gut microbiota, the immune system, and host genetics, with microbiota serving as the core of communication for differently-sourced signals. In the susceptible host, dysbiosis, characterized by the bloom of facultative anaerobic bacteria and the decline of community diversity and balance, can trigger an aberrant immune response that leads to reduced tolerance against commensal microbiota. In IBD, such dysbiosis has been profoundly proven in animal models, as well as clinic data analysis; however, it has not yet been conclusively ascertained whether dysbiosis actually promotes the disease or is simply a consequence of the inflammatory disorder. Better insight into the complex network of interactions between food, the intestinal microbiome, and host immune response will, therefore, contribute significantly to the diagnosis, treatment, and management of IBD. In this article, we review the ways in which the mutualistic circle of dietary nutrients, gut microbiota, and the immune system becomes anomalous during the IBD process, and discuss the roles of bacterial factors in shaping the intestinal inflammatory barrier and adjusting immune capacity.
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Affiliation(s)
- Qianqian Yao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Huiying Li
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Linlin Fan
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yangdong Zhang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Shengguo Zhao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Nan Zheng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Jiaqi Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Q.Y.); (H.L.); (L.F.); (Y.Z.); (S.Z.); (N.Z.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Correspondence:
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Banfi D, Moro E, Bosi A, Bistoletti M, Cerantola S, Crema F, Maggi F, Giron MC, Giaroni C, Baj A. Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:1623. [PMID: 33562721 PMCID: PMC7915037 DOI: 10.3390/ijms22041623] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
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Affiliation(s)
- Davide Banfi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Elisabetta Moro
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Annalisa Bosi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Michela Bistoletti
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Silvia Cerantola
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Francesca Crema
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Fabrizio Maggi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
- Centre of Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Andreina Baj
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
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Bodiwala V, Marshall T, Das KM, Brant SR, Seril DN. Comparison of Disease Phenotypes and Clinical Characteristics Among South Asian and White Patients with Inflammatory Bowel Disease at a Tertiary Referral Center. Inflamm Bowel Dis 2020; 26:1869-1877. [PMID: 32144933 DOI: 10.1093/ibd/izaa019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.
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Affiliation(s)
- Vimal Bodiwala
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | | | - Kiron M Das
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Steven R Brant
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Darren N Seril
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
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In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn's disease - a preliminary study. BMC Gastroenterol 2020; 20:307. [PMID: 32958038 PMCID: PMC7507689 DOI: 10.1186/s12876-020-01444-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 09/09/2020] [Indexed: 12/19/2022] Open
Abstract
Background Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota. Herein we performed the multiomics analysis by combining the large scale surveys of gut bacterial community, stool microRNA (miRNA) and short chain fatty acid (SCFA) signatures to correlate their association with the activity of Crohn’s disease (CD). Methods DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16S rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively. Results Pairwise comparisons showed that 9 and 23 taxa differed between controls and CD patients with active and inactive disease, respectively. Six taxa were common to both comparisons, whereas four taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value < 0.05; FC > 1.5) in CD patients and controls before FDR correction and 4 after. Of six SCFAs, the levels of two differed significantly (p-value < 0.05, FC > 1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with smallest error rate for controls in bacterial component and inactive disease in metabolites. Conclusion A complex interrelationship may exist between gut dysbiosis, miRNA profiling and SCFA level in response to intestinal inflammation.
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Montrose DC, Nishiguchi R, Basu S, Staab HA, Zhou XK, Wang H, Meng L, Johncilla M, Cubillos-Ruiz JR, Morales DK, Wells MT, Simpson KW, Zhang S, Dogan B, Jiao C, Fei Z, Oka A, Herzog JW, Sartor RB, Dannenberg AJ. Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis. Cell Mol Gastroenterol Hepatol 2020; 11:525-550. [PMID: 32961355 PMCID: PMC7797369 DOI: 10.1016/j.jcmgh.2020.09.008] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis. METHODS Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/- mice, respectively. RESULTS Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding a HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10-/- mice and mice infected with C rodentium. CONCLUSIONS Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution, and metabolic function of resident enteric microbiota.
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Affiliation(s)
- David C Montrose
- Department of Medicine, Weill Cornell Medicine, New York, New York
| | | | - Srijani Basu
- Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Hannah A Staab
- Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Xi Kathy Zhou
- Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York
| | - Hanhan Wang
- Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York
| | - Lingsong Meng
- Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York
| | | | - Juan R Cubillos-Ruiz
- Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York
| | - Diana K Morales
- Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York
| | - Martin T Wells
- Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York
| | - Kenneth W Simpson
- Department of Clinical Sciences, Cornell University, Ithaca, New York
| | - Shiying Zhang
- Department of Clinical Sciences, Cornell University, Ithaca, New York
| | - Belgin Dogan
- Department of Clinical Sciences, Cornell University, Ithaca, New York
| | - Chen Jiao
- Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, New York
| | - Zhangjun Fei
- Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, New York
| | - Akihiko Oka
- Departments of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina
| | - Jeremy W Herzog
- Departments of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina
| | - R Balfour Sartor
- Departments of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina
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Li R, Huang X, Liang X, Su M, Lai KP, Chen J. Integrated omics analysis reveals the alteration of gut microbe-metabolites in obese adults. Brief Bioinform 2020; 22:5882185. [PMID: 32770198 DOI: 10.1093/bib/bbaa165] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/01/2020] [Accepted: 07/02/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity, a risk to health, is a global problem in modern society. The prevalence of obesity was approximately 13% among world's adult population. Recently, several reports suggested that the interference of gut microbiota composition and function is associated with metabolic disorders, including obesity. Gut microbiota produce a board range of metabolites involved in energy and glucose homeostasis, leading to the alteration in host metabolism. However, systematic evaluation of the relationship between gut microbiota, gut metabolite and host metabolite profiles in obese adults is still lacking. In this study, we used comparative metagenomics and metabolomics analysis to determine the gut microbiota and gut-host metabolite profiles in six normal and obese adults of Chinese origin, respectively. Following the functional and pathway analysis, we aimed to understand the possible impact of gut microbiota on the host metabolites via the change in gut metabolites. The result showed that the change in gut microbiota may result in the modulation of gut metabolites contributing to glycolysis, tricarboxylic acid cycle and homolactic fermentation. Furthermore, integrated metabolomic analysis demonstrated a possible positive correlation of dysregulated metabolites in the gut and host, including l-phenylalanine, l-tyrosine, uric acid, kynurenic acid, cholesterol sulfate and glucosamine, which were reported to contribute to metabolic disorders such as obesity and diabetes. The findings of this study provide the possible association between gut microbiota-metabolites and host metabolism in obese adults. The identified metabolite changes could serve as biomarkers for the evaluation of obesity and metabolic disorders.
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Affiliation(s)
| | | | | | - Min Su
- Guilin Medical University
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Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol 2020; 145:16-27. [PMID: 31910984 DOI: 10.1016/j.jaci.2019.11.003] [Citation(s) in RCA: 509] [Impact Index Per Article: 101.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/06/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.
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Affiliation(s)
- Kerri L Glassner
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex.
| | - Bincy P Abraham
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex
| | - Eamonn M M Quigley
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex
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Snell A, Segal J, Limdi J, Banerjee R. Inflammatory bowel disease in India: challenges and opportunities. Frontline Gastroenterol 2020; 12:390-396. [PMID: 35401961 PMCID: PMC8988999 DOI: 10.1136/flgastro-2020-101500] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/06/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023] Open
Abstract
Evidence is emerging that inflammatory bowel diseases (IBDs) are becoming increasingly prevalent in developing countries, altering the previously held view that these were diseases of the West. Within this is a substantial increase in the burden of this disease in India, a matter of great importance to the country itself as well as in furthering our understanding of the disease. There is comparatively less data on this, both from the epidemiological standpoint as well as on disease pathogenesis in this particular cohort and is very much a subject matter of evolving understanding and research. This article aims to look at the changing global distribution of the disease and its implications. The Indian disease phenotype, and the aetiology of disease development will also be addressed with particular focus on differing pathogenetic processes in the Indian subpopulation, with consideration of what clues may be offered by the increasing incidence of the disease in this developing nation. Available evidence will be evaluated with the objective of providing a comprehensive overview of the development of IBD in India.
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Affiliation(s)
- Alice Snell
- Department of Gastroenterology, Northwick Park Hospital, London, UK
| | - Jonathan Segal
- Department of Gastroenterology, Saint Mary's Hospital Medical School, London, UK
| | - Jimmy Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester, UK,Manchester Academic Health Science Centre, Manchester, UK
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, Telangana, India
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Saresella M, Marventano I, Barone M, La Rosa F, Piancone F, Mendozzi L, d'Arma A, Rossi V, Pugnetti L, Roda G, Casagni E, Cas MD, Paroni R, Brigidi P, Turroni S, Clerici M. Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis. Front Immunol 2020; 11:1390. [PMID: 32733460 PMCID: PMC7358580 DOI: 10.3389/fimmu.2020.01390] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 05/29/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Butyric acid (BA) is a short-chain fatty acid (SCFA) with anti-inflammatory properties, which promotes intestinal barrier function. Medium-chain fatty acids (MCFA), including caproic acid (CA), promote TH1 and TH17 differentiation, thus supporting inflammation. Aim: Since most SCFAs are absorbed in the cecum and colon, the measurement of BA in peripheral blood could provide information on the health status of the intestinal ecosystem. Additionally, given the different immunomodulatory properties of BA and CA the evaluation of their serum concentration, as well as their ratio could be as a simple and rapid biomarker of disease activity and/or treatment efficacy in MS. Methods: We evaluated serum BA and CA concentrations, immune parameters, intestinal barrier integrity and the gut microbiota composition in patients with multiple sclerosis (MS) comparing result to those obtained in healthy controls. Results: In MS, the concentration of BA was reduced and that of CA was increased. Concurrently, the microbiota was depleted of BA producers while it was enriched in mucin-degrading, pro-inflammatory components. The reduced serum concentration of BA seen in MS patients correlated with alterations of the barrier permeability, as evidenced by the higher plasma concentrations of lipopolysaccharide and intestinal fatty acid-binding protein, and inflammation. Specifically, CA was positively associated with CD4+/IFNγ+ T lymphocytes, and the BA/CA ratio correlated positively with CD4+/CD25high/Foxp3+ and negatively with CD4+/IFNγ+ T lymphocytes. Conclusion: The gut microbiota dysbiosis found in MS is possibly associated with alterations of the SCFA/MCFA ratio and of the intestinal barrier; this could explain the chronic inflammation that characterizes this disease. SCFA and MCFA quantification could be a simple biomarker to evaluate the efficacy of therapeutic and rehabilitation procedures in MS.
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Affiliation(s)
| | | | - Monica Barone
- Microbial Ecology of Health Unit, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | | | | | | | | | | | | | - Gabriella Roda
- Departments of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Eleonora Casagni
- Departments of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | | | - Rita Paroni
- Health Sciences, University of Milan, Milan, Italy
| | - Patrizia Brigidi
- Microbial Ecology of Health Unit, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Silvia Turroni
- Microbial Ecology of Health Unit, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Mario Clerici
- IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
- Pathophysiology and Trasplantation, University of Milan, Milan, Italy
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de Alencar Junior H, Paiotti APR, de Araújo Filho HB, Oshima CTF, Miszputen SJ, Ambrogini-Júnior O. The relationship between the commensal microbiota levels and Crohn's disease activity. JGH OPEN 2020; 4:784-789. [PMID: 33102745 PMCID: PMC7578322 DOI: 10.1002/jgh3.12338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 03/18/2020] [Accepted: 03/28/2020] [Indexed: 12/30/2022]
Abstract
Background and aim Human gut microbiota play an important role in metabolism and host physiology. Perturbations of the gut microbial communities lead to the development of various diseases such as inflammatory bowel disease, celiac disease, allergic diseases, and metabolic diseases. Crohn's disease is a chronic inflammatory bowel disease characterized by periods of remission and relapse. Several studies suggest that intestinal inflammation arises due to an abnormal response of the intestinal immune system to the fecal microbiota. The goal of the study was to evaluate the relative amount of four bacterial groups in fecal samples of Crohn's disease patients and their relation to the inflammatory activity. Methods We studied stool samples of 105 individuals, 54 with Crohn's disease and 51 as a control group. The DNA extracted from the stool samples was subjected to real‐time polymerase chain reaction (qPCR) for quantification of the Bacteroidetes phylum, class Bacilli, and Bifidobacteriaceae and Enterobacteriaceae families. Results We found a significant increase in Bacteroidetes in Crohn's disease samples when compared to the control group (14 650 and 2060 CFU/ng DNA, respectively) (P = 0.014). On the other hand, we observed a significant reduction in Bacilli and Bifidobacteriaceae (13 and 58 CFU/ng DNA, respectively) (P < 0.0001). In contrast, patients without any drug treatment presented an increase of Bacilli and Bifidobacteriaceae (102 521 and 6235 CFU/ng DNA, respectively) (P < 0.0001). Conclusion The commensal bacteria were decreased in fecal samples of participants with Crohn's disease when compared to the control group. There was no relation between the disease location and/or disease activity with the microbiota.
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Affiliation(s)
| | - Ana Paula Ribeiro Paiotti
- Division of Gastroenterology Universidade Federal de São Paulo-Paulista Medical School, UNIFESP São Paulo Brazil
| | | | | | - Sender Jankiel Miszputen
- Division of Gastroenterology Universidade Federal de São Paulo-Paulista Medical School, UNIFESP São Paulo Brazil
| | - Orlando Ambrogini-Júnior
- Division of Gastroenterology Universidade Federal de São Paulo-Paulista Medical School, UNIFESP São Paulo Brazil
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Melli LCFL, Carmo-Rodrigues MSD, Araújo-Filho HB, Mello CS, Tahan S, Pignatari ACC, Solé D, Morais MBD. Gut microbiota of children with atopic dermatitis: Controlled study in the metropolitan region of São Paulo, Brazil. Allergol Immunopathol (Madr) 2020; 48:107-115. [PMID: 32061427 DOI: 10.1016/j.aller.2019.08.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/19/2019] [Accepted: 08/28/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND It is possible that imbalances in the composition of the gut microbiota or the relationship of the microbiota with the host may be implicated in the origin of allergy. Therefore, we studied the intestinal microbiota of children with atopic dermatitis (AD). METHODS Cross-sectional study with 81 children aged 5-11; 23 with AD and 58 controls. Surveys were conducted to obtain demographic, socioeconomic and neonatal data. Diagnosis of AD was made based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Eubacteria, Bacteroidetes, Firmicutes, B. fragilis, E. coli, Lactobacillus spp., S. aureus, E. faecalis, Salmonella spp., M. smithii, Bifidobacterium spp., C. difficile and C. perfringens were quantified using real-time PCR. RESULTS The analysis showed an association between presence of C. difficile (OR: 5.88; 95 % CI: 1.24; 27.98), greater abundance of bifidobacteria (OR: 11.09; 95 % CI: 2.14; 57.39) and a lower abundance of lactobacilli (OR: 0.07; 95 % CI: 0.01; 0.51) in the gut microbiota of children with AD. Counts of Eubacteria (0,05×103 and 8.49×103), B. fragilis (0.72×109 and 4.5×109), Lactobacillus spp. (0.02×108 and 0.38×108), E. coli (0.13×109 and 1.52×109) and M. smithii (0.02×108 and 0.31×108) were lower in children with AD (P<0.05). CONCLUSIONS This study confirmed that children living in the metropolitan area of São Paulo (Brazil) with AD have a different microbiota pattern with higher prevalence of C. difficile, lower abundance of Lactobacillus and greater abundance of bifidobacteria, regardless of socioeconomic status.
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Guo XY, Liu XJ, Hao JY. Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment. J Dig Dis 2020; 21:147-159. [PMID: 32040250 DOI: 10.1111/1751-2980.12849] [Citation(s) in RCA: 185] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/16/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022]
Abstract
Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.
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Affiliation(s)
- Xiao Yan Guo
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xin Juan Liu
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jian Yu Hao
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Wang F, Huang X, Chen Y, Zhang D, Chen D, Chen L, Lin J. Study on the Effect of Capsaicin on the Intestinal Flora through High-Throughput Sequencing. ACS OMEGA 2020; 5:1246-1253. [PMID: 31984282 PMCID: PMC6977284 DOI: 10.1021/acsomega.9b03798] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 12/23/2019] [Indexed: 05/04/2023]
Abstract
As a common kind of food, pepper is well known for its special effects on the physiological state of human individuals. Capsaicin, the main component of pepper, is speculated to be linked with intestinal microorganisms on account of their direct contact. Herein, we first utilized mouse models and 16S rRNA high-throughput sequencing to compare the differences in intestinal flora between mouse groups with and without capsaicin treatment by gavage. The mice in the two groups showed significantly distinct performance in terms of body weight, leukocyte count, fecal humidity, and constituent ratios of intestinal bacteria, such as Faecalibacterium, Akkermansia, Roseburia, Helicobacter, and Bacteroides species. In particular, the Faecalibacterium abundance was the most highly variable among the 5 bacterial genera. Based on statistical analysis and comparison, the variation tendency of body weight, leukocyte count, and fecal humidity was closely related to the bacteria. In conclusion, capsaicin could affect the physiological state of mice by changing the constitution of the intestinal flora.
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Affiliation(s)
- Fanghong Wang
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
| | - Xiaoyu Huang
- Department
of Preventive Dentistry, School and Hospital
of Stomatology, Fujian Medical University, Fuzhou 350002, Fujian Province, P.R. China
| | - Yueyang Chen
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
| | - Danli Zhang
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
| | - Danyi Chen
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
| | - Lingxin Chen
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
| | - Jun Lin
- Institute
of Applied Genomics, College of Biological Science and Engineering, and Fujian Key Laboratory
of Marine Enzyme Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China
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Comparison of the fecal, cecal, and mucus microbiome in male and female mice after TNBS-induced colitis. PLoS One 2019; 14:e0225079. [PMID: 31703107 PMCID: PMC6839838 DOI: 10.1371/journal.pone.0225079] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/28/2019] [Indexed: 12/15/2022] Open
Abstract
Crohn’s Disease and Ulcerative Colitis are chronic, inflammatory conditions of the digestive tract, collectively known as Inflammatory Bowel Disease (IBD). The combined influence of lifestyle factors, genetics, and the gut microbiome contribute to IBD pathogenesis. Studies of the gut microbiome have shown significant differences in its composition between healthy individuals and those with IBD. Due to the high inter-individual microbiome variation seen in humans, mouse models of IBD are often used to investigate potential IBD mechanisms and their interplay between host, microbial, and environmental factors. While fecal samples are the predominant material used for microbial community analysis, they may not be the ideal sample to use for analysis of the microbiome of mice with experimental colitis, such as that induced by 2, 4, 6 trinitrobenzesulfonic acid (TNBS). As TNBS is administered intrarectally to induce colitis and inflammation is confined to the colon in this model, we hypothesized that the microbiome of the colonic mucus would most closely correlate with TNBS colitis severity. Based on our previous research, we also hypothesized that sex would be associated with both disease severity and microbial differences in mice with chronic TNBS colitis. We examined and compared the fecal, cecal content, and colonic mucus microbiota of 8-week old male and female C57BL/6J wild-type mice prior to and after the induction of TNBS colitis via 16S rRNA gene sequencing. We found that the colonic mucus microbiome was more closely correlated with disease severity than were alterations in the fecal and cecal microbiomes. We also found that the microbiomes of the feces, cecum, and mucus were distinct, but found no significant differences that were associated with sex in either compartment. Our findings highlight the importance of sampling colonic mucus in TNBS-induced colitis. Moreover, consideration of the differential impact of sex on the microbiome across mouse strains may be critical for the appropriate application of TNBS colitis models and robust comparisons across studies in the future.
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Olalla J, García de Lomas JM, Chueca N, Pérez-Stachowski X, De Salazar A, Del Arco A, Plaza-Díaz J, De la Torre J, Prada JL, García-Alegría J, Fernández-Sánchez F, García F. Effect of daily consumption of extra virgin olive oil on the lipid profile and microbiota of HIV-infected patients over 50 years of age. Medicine (Baltimore) 2019; 98:e17528. [PMID: 31626113 PMCID: PMC6824693 DOI: 10.1097/md.0000000000017528] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 09/03/2019] [Accepted: 09/16/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Extra virgin olive oil (EVOO) has shown beneficial effects on the lipid profile and inflammatory parameters in general population. Our goal is to analyze these changes together with those of intestinal microbiota in human immunodeficiency virus (HIV)-infected patients over 50 years of age. METHODS Experimental single arm open study. HIV patients over the age of 50 with undetectable viral load were selected. EVOO was distributed among the patients so that each one consumed 50 g daily for 12 weeks. Lipid profile, C-reactive protein (CRP), and intestinal microbiota composition were analyzed at the beginning and at the end of the intervention. RESULTS Total cholesterol decreased significantly (5 mg/dL), and a nonsignificant decrease in low-density lipoprotein cholesterol (12 mg/dL), triglycerides (21 mg/dL), and CRP (1.25 mg/dL) was observed. There was a significant increase in alpha diversity after the intervention in men and a decrease in proinflammatory genera such as Dethiosulfovibrionaceae was observed. Differences were also observed in the microbiota of men and women and according to the type of antiretroviral treatment. CONCLUSION Sustained consumption of 50 g of EVOO in elderly HIV-infected patients might be associated with an improvement in lipid profile and alfa diversity of intestinal microbiota.
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Affiliation(s)
- Julián Olalla
- Servicio de Medicina Interna, Hospital Costa del Sol, Marbella
| | | | | | | | | | | | - Julio Plaza-Díaz
- Instituto de Investigación Biosanitaria IBS
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Granada
| | | | - José Luis Prada
- Servicio de Medicina Interna, Hospital Costa del Sol, Marbella
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