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Moludi J, Saber A, Zozani MA, Moradi S, Azamian Y, Hajiahmadi S, Pasdar Y, Moradi F. The Efficacy of Probiotics Supplementation on the Quality of Life of Patients with Gastrointestinal Disease: A Systematic Review of Clinical Studies. Prev Nutr Food Sci 2024; 29:237-255. [PMID: 39371511 PMCID: PMC11450280 DOI: 10.3746/pnf.2024.29.3.237] [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: 04/15/2024] [Revised: 06/16/2024] [Accepted: 06/24/2024] [Indexed: 10/08/2024] Open
Abstract
Patients with gastrointestinal (GI) disorders might benefit from probiotic supplementation to resolve their bowel symptoms and enhance their quality of life (QoL). This systematic review aimed to evaluate the effects of oral probiotic supplementation on improving QoL. Relevant studies were systematically searched in online databases, including PubMed, Scopus, Embase, ProQuest, and Google Scholar up to September 2022 using relevant keywords. Studies that were conducted on GI patients and presented QoL outcomes were included. The Revised Cochrane Risk of Bias 2 tool and the Risk Of Bias In Non-randomized Studies of Intervention tool were used to assess the risk of bias. Of the 4,555 results found in the systematic search of databases, only 36 studies were eligible for evaluation. According to this systematic review, 24 studies reported improvements, whereas 12 studies reported no improvements on QoL in GI patients supplemented with probiotics. We found that probiotics may improve the QoL of patients with GI diseases and related metabolic complications. Therefore, probiotics can be a useful supportive treatment strategy in these patients.
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Affiliation(s)
- Jalal Moludi
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
| | - Amir Saber
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
| | - Morteza Arab Zozani
- Social Determinants of Health Research Center (SDHRC), School of Health, Birjand University of Medical Sciences, Birjand 32048321, Iran
| | - Shima Moradi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
| | - Yasaman Azamian
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
| | - Salimeh Hajiahmadi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd 8915173160, Iran
| | - Yahya Pasdar
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
| | - Fardin Moradi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
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Ju X, Jiang Z, Ma J, Yang D. Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis. Nutrients 2024; 16:1727. [PMID: 38892659 PMCID: PMC11174707 DOI: 10.3390/nu16111727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 05/20/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
CONTEXT Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.
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Affiliation(s)
| | | | | | - Dong Yang
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China; (X.J.); (Z.J.); (J.M.)
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Peng X, Yi X, Deng N, Liu J, Tan Z, Cai Y. Zhishi Daozhi decoction alleviates constipation induced by a high-fat and high-protein diet via regulating intestinal mucosal microbiota and oxidative stress. Front Microbiol 2023; 14:1214577. [PMID: 37789856 PMCID: PMC10544343 DOI: 10.3389/fmicb.2023.1214577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 08/07/2023] [Indexed: 10/05/2023] Open
Abstract
Background A growing body of evidence has demonstrated that a high-fat and high-protein diet (HFHPD) causes constipation. This study focuses on understanding how the use of Zhishi Daozhi decoction (ZDD) affects the intricate balance of intestinal microorganisms. The insights gained from this investigation hold the potential to offer practical clinical approaches to mitigate the constipation-related issues associated with HFHPD. Materials and methods Mice were randomly divided into five groups: the normal (MN) group, the natural recovery (MR) group, the low-dose ZDD (MLD) group, the medium-dose ZDD (MMD) group, and the high-dose ZDD (MHD) group. After the constipation model was established by HFHPD combined with loperamide hydrochloride (LOP), different doses of ZDD were used for intervention. Subsequently, the contents of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) in serum, superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were determined. The DNA of intestinal mucosa was extracted, and 16S rRNA amplicon sequencing was used to analyze the changes in intestinal mucosal microbiota. Results After ZDD treatment, CCK content in MR group decreased and CGRP content increased, but the changes were not significant. In addition, the SOD content in MR group was significantly lower than in MLD, MMD, and MHD groups, and the MDA content in MR group was significantly higher than in MN, MLD, and MHD groups. Constipation modeling and the intervention of ZDD changed the structure of the intestinal mucosal microbiota. In the constipation induced by HFHPD, the relative abundance of pathogenic bacteria such as Aerococcus, Staphylococcus, Corynebacterium, Desulfovibrio, Clostridium, and Prevotella increased. After the intervention of ZDD, the relative abundance of these pathogenic bacteria decreased, and the relative abundance of Candidatus Arthromitus and the abundance of Tropane, piperidine, and pyridine alkaloid biosynthesis pathways increased in MHD group. Conclusion Constipation induced by HFHPD can increase pathogenic bacteria in the intestinal mucosa, while ZDD can effectively relieve constipation, reduce the relative abundance of pathogenic bacteria, and alleviate oxidative stress injury. In addition, high-dose ZDD can increase the abundance of beneficial bacteria, which is more conducive to the treatment of constipation.
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Affiliation(s)
- Xinxin Peng
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xin Yi
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Na Deng
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Jing Liu
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Zhoujin Tan
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Ying Cai
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
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Lin W, Wu D, Zeng Y, Liu Y, Yu D, Wei J, Cai Y, Lin Y, Wu B, Huang H. Characteristics of gut microbiota in male periadolescent rats with irritable bowel syndrome. Heliyon 2023; 9:e18995. [PMID: 37609414 PMCID: PMC10440515 DOI: 10.1016/j.heliyon.2023.e18995] [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: 05/24/2023] [Revised: 07/26/2023] [Accepted: 08/04/2023] [Indexed: 08/24/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, however, its effect on gut microbiota during the periadolescent period remains unclear. In this study, our objective was to investigate the characteristics of gut microbiota in male periadolescent rats with IBS induced by neonatal maternal separation (NMS). We evaluated visceral sensitivity by electromyography (EMG), analyzed gut microbiota composition using 16S rDNA gene sequencing, and examined intestinal pathological changes between control and IBS-like groups. The IBS-like group had significantly higher discharge amplitude of the external oblique muscle of the abdomen during colorectal distension (CRD) at 40- and 60 mmHg pressures. We observed differences in gut microbiota composition, with an increase in Bacteroidetes abundance and a decrease in Firmicutes in IBS-like rats. Beta-diversity analysis revealed the gut microbiota of the IBS-like group displayed higher consistent, while that of the control group exhibited substantial variation. Linear discriminant analysis effect size (LEfSe) detected 10 bacterial taxonomic clades showing statistically significant differences (7 increased and 3 decreased) in the IBS-like group. Functional analysis revealed that aminoacyl-tRNA biosynthesis and fatty acid biosynthesis were significantly altered, leading to changes in gene expression. Our findings demonstrate a definite correlation between gut microbiota dysbiosis and IBS during the male periadolescent period, with Alloprevotella and Bacteroide positively associated with high risk of IBS. The effects of specific bacterial genera may provide new insights for the development of treatments for IBS.
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Affiliation(s)
- Wei Lin
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Dongxiao Wu
- Department of Pediatrics, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yongbin Zeng
- Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yuan Liu
- Cancer Research Center Nantong, Affiliated Tumor Hospital of Nantong University, China
| | - Dajie Yu
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jianhang Wei
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yanliang Cai
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yueli Lin
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Bin Wu
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Huanhuan Huang
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Yi X, Zhou K, Jiang P, Deng N, Peng X, Tan Z. Brain-bacteria-gut axis and oxidative stress mediated by intestinal mucosal microbiota might be an important mechanism for constipation in mice. 3 Biotech 2023; 13:192. [PMID: 37205176 PMCID: PMC10185723 DOI: 10.1007/s13205-023-03580-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 04/21/2023] [Indexed: 05/21/2023] Open
Abstract
Intestinal microbiota disorder was associated with constipation. This study investigated the microbiota-gut-brain axis and oxidative stress mediated by intestinal mucosal microbiota in mice with spleen deficiency constipation. The Kunming mice were randomly divided into the control (MC) group and the constipation (MM) group. The spleen deficiency constipation model was established by gavage with Folium sennae decoction and controlled diet and water intake. The body weight, spleen and thymus index, 5-Hydroxytryptamine (5-HT) and Superoxide Dismutase (SOD) content were significantly lower in the MM group than the MC group, the content of vasoactive intestinal peptide (VIP) and malondialdehyde (MDA) content were significantly higher than the MC group. The Alpha diversity of intestinal mucosal bacteria was not changed but beta diversity was changed in mice with spleen deficiency constipation. Compared to the MC group, the relative abundance of Proteobacteria was an upward trend and the Firmicutes/Bacteroidota (F/B) value was a downward trend in the MM group. There was a significant difference in the characteristic microbiota between the two groups. In the MM group, Brevinema, Akkermansia, Parasutterella, Faecalibaculum, Aeromonas, Sphingobium, Actinobacillus, and other pathogenic bacteria were enriched. Meanwhile, there was a certain relationship between the microbiota and gastrointestinal neuropeptide and oxidative stress indicators. The community structure of intestinal mucosal bacteria in mice with spleen deficiency constipation was changed, which was characterized by the reduction of F/B value and enrichment of Proteobacteria. Microbiota-gut-brain axis may be important for spleen deficiency constipation.
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Affiliation(s)
- Xin Yi
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
| | - Kang Zhou
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
| | - Ping Jiang
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007 China
| | - Na Deng
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
| | - Xinxin Peng
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007 China
| | - Zhoujin Tan
- The Domestic First-Class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
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Hou Y, Dong L, Lu X, Shi H, Xu B, Zhong W, Ma L, Wang S, Yang C, He X, Zhao Y, Wang S. Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome. Dig Dis Sci 2022; 67:5580-5592. [PMID: 35879512 DOI: 10.1007/s10620-022-07588-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 04/14/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIMS Recent studies have shown that changes in the intestinal microbiota contribute to the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the characteristics of the fecal and intestinal mucosal microbiota in IBS patients, and the correlation between microbiota and clinical manifestations. METHODS Fecal and intestinal mucosal samples were collected from 14 constipation-predominant IBS (IBS-C) patients, 20 diarrhea-predominant IBS (IBS-D) patients, and 20 healthy controls (HCs). 16S rRNA gene sequencing and fluorescence in situ hybridization were used for the analysis of samples. RESULTS Community richness and diversity of the fecal microbiota in IBS patients were significantly reduced compared with the HCs. The mucosal samples in IBS patients showed decreased Bifidobacterium and increased Bacteroides caccae compared with HCs; Eubacterium and Roseburia were decreased in IBS-C patients and increased in IBS-D patients. A comparison of the fecal and mucosal microbiota in IBS patients showed significantly increased Bifidobacterium in fecal samples and a decrease in mucosal samples in IBS-C patients; Bacteroides caccae and Roseburia were significantly reduced in fecal samples and increased in mucosal samples of IBS patients. A correlation between microbiota and clinical manifestations in IBS patients showed that Bacteroides caccae and Roseburia in fecal samples and Bifidobacterium and Eubacterium in mucosal samples were associated with abdominal pain and distention. CONCLUSIONS Distinct differences exist between the fecal and intestinal mucosal microbiota in IBS patients, with the changes in the latter appearing more consistent with the pathophysiology of IBS. Changes in intestinal microbiota were associated with the clinical manifestations in IBS.
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Affiliation(s)
- Yangfan Hou
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China.,Pulmonary and Critical Care Medicine, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Lei Dong
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Xiaolan Lu
- Department of Gastroenterology, Shanghai Pudong Hospital, Shanghai, 201399, China
| | - Haitao Shi
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Bing Xu
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Wenting Zhong
- International Medical Ward, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, 710061, China
| | - Lin Ma
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Shuhui Wang
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Caifeng Yang
- Departments of Gastroenterology, Xi'an City First Hospital, Xi'an, 710002, China
| | - Xinyi He
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Yidi Zhao
- Emergency Department, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Shenhao Wang
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China.
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Tkach S, Dorofeyev A, Kuzenko I, Sulaieva O, Falalyeyeva T, Kobyliak N. Fecal microbiota transplantation in patients with post-infectious irritable bowel syndrome: A randomized, clinical trial. Front Med (Lausanne) 2022; 9:994911. [PMID: 36341232 PMCID: PMC9631772 DOI: 10.3389/fmed.2022.994911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 10/03/2022] [Indexed: 11/28/2022] Open
Abstract
Introduction Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified. Aim The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT’s safety, clinical and microbiological efficacy in patients with PI-IBS. Materials and methods Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale). Results FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted. Conclusion This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.
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Affiliation(s)
- Sergii Tkach
- Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine
| | - Andrii Dorofeyev
- Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine
| | - Iurii Kuzenko
- Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine
| | | | - Tetyana Falalyeyeva
- Medical Laboratory CSD, Kyiv, Ukraine
- Educational-Scientific Center, “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Nazarii Kobyliak
- Medical Laboratory CSD, Kyiv, Ukraine
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
- *Correspondence: Nazarii Kobyliak,
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Grozić A, Coker K, Dussik CM, Sabir MS, Sabir Z, Bradley A, Zhang L, Park J, Yale S, Kaneko I, Hockley M, Harris LA, Lunsford TN, Sandrin TR, Jurutka PW. Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D. PLoS One 2022; 17:e0275683. [PMID: 36264926 PMCID: PMC9584396 DOI: 10.1371/journal.pone.0275683] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 09/21/2022] [Indexed: 11/06/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.
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Affiliation(s)
- Aleksandra Grozić
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Keaton Coker
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Christopher M. Dussik
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Marya S. Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Zhela Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Arianna Bradley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lin Zhang
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Jin Park
- Biodesign Institute, Arizona State University, Tempe, AZ, United States of America
| | - Steven Yale
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL, United States of America
| | - Ichiro Kaneko
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
| | - Maryam Hockley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lucinda A. Harris
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Tisha N. Lunsford
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Todd R. Sandrin
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Julie Ann Wrigley Global Futures Laboratory, Arizona State University, Tempe, AZ, United States of America
| | - Peter W. Jurutka
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
- * E-mail:
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Mazzawi T, Hausken T, Refsnes PF, Hatlebakk JG, Lied GA. The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study. Microorganisms 2022; 10:microorganisms10091819. [PMID: 36144420 PMCID: PMC9503104 DOI: 10.3390/microorganisms10091819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/04/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.
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Affiliation(s)
- Tarek Mazzawi
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- Faculty of Medicine, Al-Balqa Applied University, 19117 Al-Salt, Jordan
- Correspondence:
| | - Trygve Hausken
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Per Førde Refsnes
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Gülen Arslan Lied
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
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10
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Sagkan-Ozturk A, Arpaci A. The comparison of changes in fecal and mucosal microbiome in metabolic endotoxemia induced by a high-fat diet. Anaerobe 2022; 77:102615. [PMID: 35850456 DOI: 10.1016/j.anaerobe.2022.102615] [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: 03/02/2022] [Revised: 06/02/2022] [Accepted: 07/12/2022] [Indexed: 11/25/2022]
Abstract
The aim of this study was to compare the mucosal and fecal microbiota in a high fat diet-induced metabolic endotoxemia (ME) model and to identify potential species that represent dysbiosis and might mediate the inflammatory process. Fourteen male wistar albino rats were fed a standard diet (n = 7) and a high-fat diet (HFD) (n = 7). The standard diet (2600 kcal/kg) contained 3% of energy from fat and HFD (6740 kcal/kg) contained 67% beef tallow. After feeding for 12 weeks, all rats were sacrificed after fasting for 12 h and blood samples were collected. Fresh faecal samples and descending colon samples of rats were collected in sterile plastic tubes using a clean technique, immediately snap-frozen in liquid nitrogen, and then stored at -80 °C until used for analysis. Serum glucose, TRG, TLR4, LPS, and fecal LPS increased in the HFD group. On the contrary, HDL was higher and statistically significant in the CD group. The levels of IL-6 and TNF-α in the colon tissue of the HFD group were significant. The HFD group caused a significant increase in LPS levels in serum and feces. In addition, the gut and mucosal microbiome were positively/negatively correlated with the ME markers (IL6, TNFα, LPS). The results showed that gut and mucosal microbiome changes were associated with HFD. These changes were dense at species levels. The current study demonstrated changes in gut and mucosal microbiota in HFD-induced metabolic endotoxemia.
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Affiliation(s)
- Aliye Sagkan-Ozturk
- Department of Internal Medicine, Faculty of Veterinary Medicine, University of Hatay Mustafa Kemal, Hatay, Turkey; Department of Molecular Biochemistry and Genetic (Medicine), Institute of Health Sciences, University of Hatay Mustafa Kemal, Hatay, Turkey.
| | - Abdullah Arpaci
- Department of Biochemistry, Faculty of Medicine, University of Hatay Mustafa Kemal, Hatay, Turkey.
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11
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Foster-Nyarko E, Pallen MJ. The microbial ecology of Escherichia coli in the vertebrate gut. FEMS Microbiol Rev 2022; 46:fuac008. [PMID: 35134909 PMCID: PMC9075585 DOI: 10.1093/femsre/fuac008] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 11/13/2022] Open
Abstract
Escherichia coli has a rich history as biology's 'rock star', driving advances across many fields. In the wild, E. coli resides innocuously in the gut of humans and animals but is also a versatile pathogen commonly associated with intestinal and extraintestinal infections and antimicrobial resistance-including large foodborne outbreaks such as the one that swept across Europe in 2011, killing 54 individuals and causing approximately 4000 infections and 900 cases of haemolytic uraemic syndrome. Given that most E. coli are harmless gut colonizers, an important ecological question plaguing microbiologists is what makes E. coli an occasionally devastating pathogen? To address this question requires an enhanced understanding of the ecology of the organism as a commensal. Here, we review how our knowledge of the ecology and within-host diversity of this organism in the vertebrate gut has progressed in the 137 years since E. coli was first described. We also review current approaches to the study of within-host bacterial diversity. In closing, we discuss some of the outstanding questions yet to be addressed and prospects for future research.
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Affiliation(s)
- Ebenezer Foster-Nyarko
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, United Kingdom
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
| | - Mark J Pallen
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom
- School of Veterinary Medicine, University of Surrey, Guildford, Surrey, GU2 7AL, United Kingdom
- School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TU, United Kingdom
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12
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Ji L, Zhao X, Zhang Y, Zhao P, Gong R, Li F, Huang H. Efficacy and safety of Qinghua Zhixie Decoction against diarrhea-predominate irritable bowel syndrome: A protocol for a randomized controlled trial. Medicine (Baltimore) 2022; 101:e28895. [PMID: 35244043 PMCID: PMC8896428 DOI: 10.1097/md.0000000000028895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Diarrhea-predominant irritable bowel syndrome (D-IBS) is the main subtypes of irritable bowel syndrome (IBS). In recent years, more than half of IBS patients have received complementary and alternative medicine. Traditional Chinese herbal formula is widely used in Asia, and clinical studies have also found that Chinese herbal formula could significantly improve abdominal pain and diarrhea. We plan to carry out a randomized, controlled, double blind, clinical studies to observe the clinical efficacy of Qinghua Zhixie decoction in the treatment of D-IBS. METHODS Four hundred sixty-four participants will be randomly assigned to the treatment group and control group. Patients in both groups would take medications and stimulations simultaneously. The outcomes of IBS symptom severity score, quality of life, psychological states, and recurrence rate will be recorded. Statistics will be analyzed with the SPSS 22.0. CONCLUSIONS The findings of the study will identify the safety and efficacy of Qinghua Zhixie decoction in the treatment of D-IBS. TRIAL REGISTRATION OSF REGISTRATION NUMBER DOI 10.17605/OSF.IO/C8MHW.
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Affiliation(s)
- Lijiang Ji
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China
| | - Xiaoying Zhao
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuyan Zhang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ping Zhao
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China
| | - Rui Gong
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Fang Li
- Department of Gastroenterology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
| | - Hua Huang
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China
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13
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Current Status and Future Therapeutic Options for Fecal Microbiota Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58010084. [PMID: 35056392 PMCID: PMC8780626 DOI: 10.3390/medicina58010084] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/23/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022]
Abstract
The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.
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14
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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15
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Yang F, Wu J, Ye NY, Miu J, Yan J, Liu LN, Ye B. Association of Fecal Microbiota with Irritable Bowel Syndrome-Diarrhea and Effect of Traditional Chinese Medicine for Its Management. Gastroenterol Res Pract 2021; 2021:7035557. [PMID: 34691175 PMCID: PMC8529176 DOI: 10.1155/2021/7035557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/24/2021] [Accepted: 08/28/2021] [Indexed: 12/12/2022] Open
Abstract
Changes in intestinal microbiota have been linked to the development of diarrhea predominant irritable bowel syndrome (IBS-D). In order to better elucidate the relationship between intestinal microbiota changes and IBS-D, we compared fecal microbiota of IBS-D rats and healthy control using pyrosequencing of bacterial 16S rRNA gene targeted. Furthermore, we explored the effects of different traditional Chinese medicine (TCM) on intestinal microbiota of IBS-D in dose-dependent manner. Our results showed that there was no significant difference in fecal microbial community diversity among the healthy control group, IBS-D rats and IBS-D rats treated with traditional Chinese medicine, but the fecal microbial composition at different taxonomic levels have changed among these groups. Interestingly, the weight of IBS-D rats treated with moderate doses (13.4 g/kg) of TCM increased significantly, and the diarrhea-related symptoms improved significantly, which may be related to the enrichment in Deferribacteres, Proteobacteria, Tenericutes, Lachnospiraceae, and Ruminococcaceae and the reduction in Lactobacillus in fecal samples.
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Affiliation(s)
- Fang Yang
- Department of Stomach (Gastroenterology) Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital to Nanjing University of Chinese Medicine, Nantong 226000, China
| | - Jiaqi Wu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Ning-Yuan Ye
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Jing Miu
- Nantong University, Nantong 226000, China
| | - Jing Yan
- Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Li-Na Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Bai Ye
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
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16
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Abstract
Gut microbiota plays a vital role in human health. The number of microorganisms inhabiting the gastrointestinal (GI) tract has been estimated to exceed 1013. The dominant genera in the human intestine are Firmicutes (more than 180 species of Lactobacillus), Actinobacteria (among others the Bifidobacteriae), Bacteroidetes (the most important is B. fragilis) and Proteobacteria (E. coli, Salmonella, Yersinia, Shigella, Vibrio, Haemophilus, etc.), but the composition of the flora varies individually, as well as in relation to factors such as host genetics, stress, diet, antibiotics and early childhood experiences. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGIDs), which has now been renamed disorders of gut-brain interaction, which affect a large number of people worldwide. It is characterized by abdominal pain and altered bowel habits in the absence of obvious anatomic or physiologic abnormalities. It poses a negative economic impact to the global health care system in addition to reducing the quality of life in patients. The pathophysiology of IBS is not fully understood. In IBS subjects gut microbiota relative to healthy controls was observed with an increase in Enterobacteriaceae, Ruminococcus, Clostridium, Dorea species and a decrease of Lactobacillus, Bifidobacterium, and Faecalibacterium species. IBS with diarrhea predominance (IBS-D) IBS with mixed bowel habits (IBS-M) share similarities in the microbial profile. Recent studies suggest that perturbations within "brain-gut-microbiota" axis may lead to IBS development. The aim of this review was to highlight the potential role of gut microbiota on pathophysiological mechanisms underlying IBS.
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Affiliation(s)
- Cristina M Sabo
- Second Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania -
| | - Dan L Dumitrascu
- Second Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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17
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Abstract
Advances in bioinformatics have facilitated investigation of the role of gut microbiota in patients with irritable bowel syndrome (IBS). This article describes the evidence from epidemiologic and clinical observational studies highlighting the link between IBS and gut microbiome by investigating postinfection IBS, small intestinal bacterial overgrowth, and microbial dysbiosis. It highlights the effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS, including gut-brain axis, visceral hypersensitivity, motility, epithelial barrier, and immune activation. In addition, it summarizes the current evidence on microbiome-guided therapies in IBS, including probiotics, antibiotics, diet, and fecal microbiota transplant.
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Affiliation(s)
- Prashant Singh
- Division of Gastroenterology and Hepatology, University of Michigan, MSBR1, Room 6520 B, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
| | - Anthony Lembo
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Rabb/Rose 1, 330 Brookline Avenue, Boston, MA 02215, USA
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18
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Jia M, Zhang Y, Gao Y, Ma X. Effects of Medium Chain Fatty Acids on Intestinal Health of Monogastric Animals. Curr Protein Pept Sci 2021; 21:777-784. [PMID: 31889482 DOI: 10.2174/1389203721666191231145901] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/25/2019] [Accepted: 10/08/2019] [Indexed: 11/22/2022]
Abstract
Medium-chain fatty acids (MCFAs) are the main form of Medium Chain Triglycerides (MCTs) utilized by monogastric animals. MCFAs can be directly absorbed and supply rapid energy to promote the renewal and repair of intestinal epithelial cells, maintain the integrity of intestinal mucosal barrier function, and reduce inflammation and stress. In our review, we pay more attention to the role of MCFAs on intestinal microbiota and mucosa immunity to explore MCFA's positive effect. It was found that MCFAs and their esterified forms can decrease pathogens while increasing probiotics. In addition, being recognized via specific receptors, MCFAs are capable of alleviating inflammation to a certain extent by regulating inflammation and immune-related pathways. MCFAs may also have a certain value to relieve intestinal allergy and inflammatory bowel disease (IBD). Unknown mechanism of various MCFA characteristics still causes dilemmas in the application, thus MCFAs are used generally in limited dosages and combined with short-chain organic acids (SOAs) to attain ideal results. We hope that further studies will provide guidance for the practical use of MCFAs in animal feed.
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Affiliation(s)
- Manyi Jia
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University,
No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Yucheng Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University,
No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Yuqi Gao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University,
No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Xi Ma
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University,
No. 2 Yuanmingyuan West Road, Beijing 100193, China
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19
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Nearing JT, Comeau AM, Langille MGI. Identifying biases and their potential solutions in human microbiome studies. MICROBIOME 2021; 9:113. [PMID: 34006335 PMCID: PMC8132403 DOI: 10.1186/s40168-021-01059-0] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 03/24/2021] [Indexed: 05/13/2023]
Abstract
Advances in DNA sequencing technology have vastly improved the ability of researchers to explore the microbial inhabitants of the human body. Unfortunately, while these studies have uncovered the importance of these microbial communities to our health, they often do not result in similar findings. One possible reason for the disagreement in these results is due to the multitude of systemic biases that are introduced during sequence-based microbiome studies. These biases begin with sample collection and continue to be introduced throughout the entire experiment leading to an observed community that is significantly altered from the true underlying microbial composition. In this review, we will highlight the various steps in typical sequence-based human microbiome studies where significant bias can be introduced, and we will review the current efforts within the field that aim to reduce the impact of these biases. Video abstract.
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Affiliation(s)
- Jacob T Nearing
- Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - André M Comeau
- Integrated Microbiome Resource, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Morgan G I Langille
- Integrated Microbiome Resource, Dalhousie University, Halifax, Nova Scotia, Canada.
- Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
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20
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The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling. Int J Mol Sci 2021; 22:ijms22041965. [PMID: 33671197 PMCID: PMC7922330 DOI: 10.3390/ijms22041965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease.
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21
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Boland K, Bedrani L, Turpin W, Kabakchiev B, Stempak J, Borowski K, Nguyen G, Steinhart AH, Smith MI, Croitoru K, Silverberg MS. Persistent Diarrhea in Patients With Crohn's Disease After Mucosal Healing Is Associated With Lower Diversity of the Intestinal Microbiome and Increased Dysbiosis. Clin Gastroenterol Hepatol 2021; 19:296-304.e3. [PMID: 32220613 PMCID: PMC7511440 DOI: 10.1016/j.cgh.2020.03.044] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 03/05/2020] [Accepted: 03/13/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In patients with inflammatory bowel diseases (IBDs), symptoms do not always associate with the severity of endoscopic inflammation and can persist after mucosal healing. We investigated whether symptoms in patients with successfully treated IBD are related to the composition of the intestinal microbiome. METHODS We analyzed 590 tissue biopsy specimens from 215 patients with IBD and 48 healthy individuals (controls). We obtained mucosal biopsy specimens from 2 colon sites (ascending and rectosigmoid) and from the terminal ileum along with clinical data. Bacterial DNA was extracted from the biopsy specimens and the V4 region of 16s ribosomal RNA sequenced by Miseq and processed using the QIIME v1.9 pipeline. RESULTS Mucosal biopsy specimens from patients with Crohn's disease (CD) who achieved mucosal healing (Mayo scores of 0-1 or segmental endoscopic severity CD scores of 0-5) had lower Chao1 diversity than biopsy specimens from patients with ulcerative colitis (UC) or unclassified IBD (IBD-U), or controls. After endoscopic evidence of improvement in patients with UC or IBD-U, diversity of the tissue-associated microbiota did not differ significantly from that of controls. Colon biopsy specimens from patients with CD had lower microbial diversity, before and after healing (segmental endoscopic severity CD scores, 0-2), than colon biopsy specimens from controls (P < .002). In patients with CD who achieved mucosal healing, residual clinical activity (CD activity index scores >150; P = .03) and persistent diarrhea were associated with reduced microbial diversity (P = .01). Continued diarrhea was associated with a trend toward dysbiosis, based on the microbial dysbiosis index (P = .059). In patients with UC or IBD-U with moderate to severe inflammation, increasing severity of diarrhea was associated with reduced microbial diversity (P = .03). CONCLUSIONS In an analysis of biopsy specimens from patients with IBD and controls, we found that despite endoscopic evidence of improvement or remission, α-diversity of the tissue-associated intestinal microbiome remained lower in patients with CD than in controls. This observation, along with the reduced Chao1 diversity and greater dysbiosis in intestinal microbiota of patients with residual symptoms of IBD, indicates that microbiome composition could be associated with persistent diarrhea.
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Affiliation(s)
- Karen Boland
- Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
| | - Larbi Bedrani
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Williams Turpin
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Boyko Kabakchiev
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Joanne Stempak
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Krzysztof Borowski
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Geoffrey Nguyen
- Division of Gastroenterology, Mount Sinai Hospital,
University of Toronto, Canada
| | - A Hillary Steinhart
- Division of Gastroenterology, Mount Sinai Hospital,
University of Toronto, Canada
| | - Michelle I Smith
- Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Kenneth Croitoru
- Division of Gastroenterology, Mount Sinai Hospital,
University of Toronto, Canada,Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Mark S Silverberg
- Division of Gastroenterology, Mount Sinai Hospital,
University of Toronto, Canada,Zane Cohen Centre for Digestive Diseases,
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
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22
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Quitadamo P, Isoldi S, Mallardo S, Zenzeri L, Di Nardo G. Scientific Evidence for the Treatment of Children with Irritable Bowel Syndrome. Curr Pediatr Rev 2021; 17:92-102. [PMID: 33504308 DOI: 10.2174/1573396317666210127123330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/20/2020] [Accepted: 11/05/2020] [Indexed: 11/22/2022]
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastro-intestinal disorders which significantly impacts the quality of life of affected children. Abdominal pain improved by defecation, associated with a change in stool form and frequency, represents its specific clinical marker. Even if a number of potential patho-physiological mechanisms have been described, the exact underlying etiology of IBS is so far unclear. Likewise, no optimal treatment has ever been found neither for adult nor for pediatric patients. Current therapeutic options include drugs, dietary interventions and biopsychosocial therapies. The present review aims at evaluating the scientific evidence supporting the efficacy of these treatments for children with IBS.
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Affiliation(s)
- Paolo Quitadamo
- Department of Pediatrics, A.O.R.N. Santobono-Pausilipon, Naples, Italy
| | - Sara Isoldi
- Maternal and Child Health Department, Sapienza - University of Rome, Santa Maria Goretti Hospital, Polo Pontino, Latina, Italy
| | - Saverio Mallardo
- Maternal and Child Health Department, Sapienza - University of Rome, Santa Maria Goretti Hospital, Polo Pontino, Latina, Italy
| | - Letizia Zenzeri
- Pediatric Emergency Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Giovanni Di Nardo
- Chair of Pediatrics, Pediatric Gastroenterology and Endoscopy Unit, NESMOS Department, Faculty School of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
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23
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Microbiome Analysis from Paired Mucosal and Fecal Samples of a Colorectal Cancer Biobank. Cancers (Basel) 2020; 12:cancers12123702. [PMID: 33317136 PMCID: PMC7762977 DOI: 10.3390/cancers12123702] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/05/2020] [Accepted: 12/08/2020] [Indexed: 12/14/2022] Open
Abstract
Simple Summary The role of gut microbiota in colorectal cancer is subject to extensive research. The aim of this study was to assess the feasibility of DNA extraction and microbiome profiling of samples from different sample sites, tissue sites and storage duration of a colorectal cancer biobank. Mucosa samples, mucosal scrapings and feces as well as different tissue sites (tumor, normal mucosa) were analyzed. Microbiome analysis could be successfully performed in most of the samples (overall 93.3%) with sufficient numbers of high-quality reads. There were no differences between sample sites, while in some measures, significant differences were found between tumor and normal mucosa. Samples stored for up to eight years were used and storage conditions had no significant influence on the results. Microbiome analysis can be carried out successfully in fecal, normal mucosal and tumor samples stored long term in a colorectal cancer biobank, hence large retrospective microbiome association studies are feasible. Abstract The role of gut microbiota in colorectal cancer is subject to extensive research. Before usage of biorepositories for microbiome studies, it is crucial to evaluate technical feasibility of microbiome profiling from various biospecimens. The aim of this study was to assess the feasibility of DNA-extraction and microbiome profiling of samples from different sample sites, tissue sites and storage duration of a colorectal cancer biobank. Mucosa samples, mucosal scrapings and feces as well as different tissue sites (tumor, normal mucosa) were analyzed. 16S rRNA gene-based microbiome profiling with taxonomic assignment was performed on the Illumina MiSeq (Illumina, San Diego, USA) platform from stored snap frozen samples. For statistical analysis, α- and β-diversity measures, PCoA, permutational multivariate analysis of variance and graphical representation were performed. Microbiome analysis could be successfully performed in most of the samples (overall 93.3%) with sufficient numbers of high-quality reads. There were no differences between sample sites, while in some measures significant differences were found between tumor and normal mucosa (α-diversity, Shannon/Simpson Indices p = 0.028/0.027, respectively). Samples stored for up to eight years were used and storage conditions had no significant influence on the results. Tumor and tissue samples of a biobank stored long term can be successfully used for microbiome analysis. As large sample sizes are needed for association studies to evaluate microbial impact on tumorigenesis or progression of colorectal cancer, an already established biorepository may be a useful alternative to prospective clinical studies.
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24
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Lötstedt B, Boyer D, Visner G, Freiberger D, Lurie M, Kane M, DiFilippo C, Lundeberg J, Narvaez-Rivas M, Setchell K, Alm E, Rosen R. The impact of gastrointestinal dysmotility on the aerodigestive microbiome of pediatric lung transplant recipients. J Heart Lung Transplant 2020; 40:210-219. [PMID: 33349521 DOI: 10.1016/j.healun.2020.11.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 11/12/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Delayed gastric emptying has been associated with increased graft rejection, although the mechanism of this association is not known. This study aims to investigate the interrelationship between delays in gastrointestinal motility and the diversity and composition of gastric, oropharyngeal, and lung microbiomes in pediatric lung transplant recipients. METHODS We prospectively recruited 23 pediatric lung transplant recipients and 98 pediatric patients with respiratory symptoms undergoing combined endoscopy and bronchoscopy. Gastric, oropharyngeal, and bronchoalveolar lavage samples were collected for 16S sequencing. Gastric samples were also analyzed for bile composition using liquid chromatography. RESULTS Patients who underwent lung transplantation had significantly reduced alpha diversity in gastric and oropharyngeal sites compared with patients with respiratory symptoms. This reduction in alpha diversity was especially evident in gastric samples in patients with delayed gastric emptying defined as abnormal gastric emptying on nuclear scintigraphy or as an elevation in gastric bile concentration (p ≤ 0.05). Whereas monocolonies were seen in the lungs of patients who underwent transplantation, these were not the same microbes seen in the stomach; the microbial overlap between lung and gastric samples within patients was low, and data indicated high individual variation between lung transplant recipients. Other contributors to reduced alpha diversity included antibiotics in combination with proton pump inhibitors, especially in gastric and oropharyngeal samples. CONCLUSIONS Lung transplant recipients have reduced microbial diversity in gastric fluid (GF) and oropharynx compared with patients who did not undergo lung transplantation. The decreased alpha diversity in GF may be associated with dysmotility.
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Affiliation(s)
- Britta Lötstedt
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Debra Boyer
- Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts
| | - Gary Visner
- Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts
| | - Dawn Freiberger
- Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts
| | - Margot Lurie
- Aerodigestive Center, Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts
| | - Madeline Kane
- Aerodigestive Center, Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts
| | - Courtney DiFilippo
- Aerodigestive Center, Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts
| | - Joakim Lundeberg
- Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Monica Narvaez-Rivas
- Division of Gastroenterology, Cincinnati Children's Medical Center, Cincinnati, Ohio
| | - Kenneth Setchell
- Division of Gastroenterology, Cincinnati Children's Medical Center, Cincinnati, Ohio
| | - Eric Alm
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
| | - Rachel Rosen
- Aerodigestive Center, Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts.
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25
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Jeffery IB, O'Herlihy E, Shanahan F, O' Toole PW. Microbiome alterations in IBS. Gut 2020; 69:2263-2264. [PMID: 32139549 DOI: 10.1136/gutjnl-2020-320919] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 02/20/2020] [Accepted: 02/24/2020] [Indexed: 12/12/2022]
Affiliation(s)
| | | | - Fergus Shanahan
- 4D Pharma Cork Ltd, Cork, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Paul W O' Toole
- 4D Pharma Cork Ltd, Cork, Ireland .,School of Microbiology and APC Microbiome Ireland, University College Cork, Cork, Ireland
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26
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Mucosa-Associated Microbiota in Ileoanal Pouches May Contribute to Clinical Symptoms, Particularly Stool Frequency, Independent of Endoscopic Disease Activity. Clin Transl Gastroenterol 2020; 10:1-7. [PMID: 31117112 PMCID: PMC6602764 DOI: 10.14309/ctg.0000000000000038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA). However, there is a poor correlation between symptoms and endoscopic appearance of the pouch, and many patients can have debilitating symptoms in the absence of overt inflammation. It is unknown whether these clinical symptoms are independently associated with the microbiota. The objective of this work was to examine whether the individual clinical components of the pouch activity scoring systems are associated with specific microbiota. METHODS Pouch biopsies from 233 patients (50% male, 100% IPAA/ulcerative colitis) post-IPAA were included. Clinical phenotyping was performed, and patients were classified using both clinical and endoscopic components of the Pouch Activity Scale. Scoring for symptoms examined 24-hour stool frequency, urgency, incontinence, and rectal bleeding as described by the Pouchitis Disease Activity Index Score. RESULTS In the absence of inflammation, an increase in stool frequency reported over 24 hours was associated with a decrease in Bacteroidetes relative abundance, and this was the strongest association found. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis in inflamed groups showed that an increase in 24-hour stool frequency was associated with an increase in biofilm formation. DISCUSSION These findings indicate that in patients with IPAA, the composition of mucosa-associated microbiota of the pouch may contribute to clinical symptoms, particularly stool frequency, independent of endoscopic disease activity.
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27
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Schoster A, Weese JS, Gerber V, Nicole Graubner C. Dysbiosis is not present in horses with fecal water syndrome when compared to controls in spring and autumn. J Vet Intern Med 2020; 34:1614-1621. [PMID: 32588473 PMCID: PMC7379055 DOI: 10.1111/jvim.15778] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 03/24/2020] [Accepted: 03/24/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Fecal water syndrome (FWS) is long-standing and common in horses, particularly in central Europe. No large epidemiological data sets exist, and the cause remains elusive. Dysbiosis could play a role in pathogenesis. OBJECTIVES To evaluate whether dysbiosis is present in horses with FWS when compared to stable-matched control horses in spring and autumn. ANIMALS Fecal samples were collected from horses with FWS (n = 16; 9 mares, 7 geldings) and controls (n = 15; 8 mares, 7 geldings). METHODS The bacterial microbiome of samples collected in spring and autumn of 2016 was analyzed using high-throughput sequencing. Differences in relative abundance of bacterial taxa, alpha diversity, and beta diversity indices were assessed between horses with FWS and controls based on season. RESULTS Differences in microbial community composition based on time point and health status were not observed on any taxonomic level. Limited differences were seen on linear discriminant analysis effect size analysis. No difference in alpha diversity indices was observed including richness, diversity based on health status, or time point. No effect of health status on microbial community membership structure was observed. CONCLUSIONS AND CLINICAL IMPORTANCE Limited differences were found in the bacterial microbiota of horses with and without FWS, regardless of season. Further research is needed to elucidate the role of microbiota in the development of FWS.
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Affiliation(s)
| | - J. Scott Weese
- University of Guelph, University of GuelphGuelphOntarioCanada
| | - Vinzenz Gerber
- Vetsuisse Faculty, University of BernDepartment of Veterinary MedicineBernSwitzerland
| | - Claudia Nicole Graubner
- Equine Clinic ‐ Vetsuisse Faculty, University of BernDepartment of Veterinary MedicineBerneSwitzerland
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28
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Moore RL, Geraghty AA, Feehily C, Saldova R, Murphy EF, Van Sinderen D, Cotter PD, McAuliffe FM. Can a probiotic supplement in pregnancy result in transfer to the neonatal gut: A systematic review. Acta Obstet Gynecol Scand 2020; 99:1269-1277. [PMID: 32400910 DOI: 10.1111/aogs.13899] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 05/04/2020] [Accepted: 05/06/2020] [Indexed: 12/23/2022]
Abstract
INTRODUCTION The establishment of the neonatal gut microbiome is a crucial step that may have lifelong health implications. We aimed to systematically review evidence on maternal probiotic supplementation during pregnancy and vertical transfer of the corresponding strain to the infant gut. MATERIAL AND METHODS Medline, CINAHL, Embase, Web of Science, and OVID were searched from inception to September 2018. Studies of maternal probiotic supplementation for a minimum duration of 2 weeks and analyses of neonatal stool samples were included. The primary outcome was presence of the specific probiotic strain in the infant stool. Electronic databases were searched for relevant studies and references were cross-checked. Risk of bias among included studies was assessed and data were extracted independently by two authors. RESULTS Three studies were included in the review. Only one study was identified involving prenatal maternal probiotic supplementation alone. Neonatal colonization with the maternally administered probiotic was not demonstrated but supplementation with the probiotic influenced levels of a bacterial strain other than that found in the probiotic product. The other two studies identified included both prenatal and postnatal supplementation of either mother or infant. All three studies reported employing strain-specific isolation methodology to isolate the supplemented bacterial strain in infant stool but none used whole metagenome shotgun sequencing. CONCLUSIONS Few studies investigating transfer of a specific probiotic bacterial strain from mother to infant were identified, showing inconclusive evidence of vertical transfer.
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Affiliation(s)
- Rebecca L Moore
- UCD Perinatal Research Center, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Aisling A Geraghty
- UCD Perinatal Research Center, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Conor Feehily
- APC Microbiome Ireland, National University of Ireland, Cork, Ireland.,Teagasc Food Research Center, Moorepark, Fermoy, Cork, Ireland
| | - Radka Saldova
- The National Institute for Bioprocessing, Research, and Training (NIBRT), Dublin, Ireland
| | - Eileen F Murphy
- Precision Biotics Ltd, Cork Airport Business Park, Cork, Ireland
| | - Douwe Van Sinderen
- APC Microbiome Ireland, National University of Ireland, Cork, Ireland.,School of Microbiology, National University of Ireland, Cork, Ireland
| | - Paul D Cotter
- APC Microbiome Ireland, National University of Ireland, Cork, Ireland.,Teagasc Food Research Center, Moorepark, Fermoy, Cork, Ireland
| | - Fionnuala M McAuliffe
- UCD Perinatal Research Center, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
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Abstract
Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain-gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.
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Affiliation(s)
- Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Anthony Lembo
- Division of Gastroenterology, Beth Israel Deaconess Hospital, Boston, MA, USA
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30
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Lembo A, Rao SSC, Heimanson Z, Pimentel M. Abdominal Pain Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea. Clin Transl Gastroenterol 2020; 11:e00144. [PMID: 32352714 PMCID: PMC7145050 DOI: 10.14309/ctg.0000000000000144] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 12/20/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Abdominal pain is the principal symptom of irritable bowel syndrome (IBS). This analysis examined abdominal pain response in adults with IBS with diarrhea (IBS-D) receiving the nonsystemic antibiotic rifaximin. METHODS In the Targeted Nonsystemic Antibiotic Rifaximin Gut-Selective Evaluation of Treatment for IBS-D 3 trial, adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by the 4-week post-treatment phase assessing abdominal pain and stool consistency response. Responders were followed for up to 18 additional weeks; patients with recurrence were randomly assigned to receive two 2-week courses of double-blind rifaximin 550 mg 3 times daily or placebo, separated by 10 weeks. Analyses evaluated mean weekly improvements from baseline (e.g., ≥30%, ≥40%, and ≥50%) in abdominal pain during the 4-week post-repeat-treatment phases. RESULTS Of the 2,438 evaluable patients, 1,384 (56.8%) had abdominal pain response to open-label rifaximin (≥30% improvement from baseline in the mean weekly abdominal pain score during ≥2 of the first 4 weeks post-treatment). Weekly decrease (improvement) in responders' mean abdominal pain score (scale range, 0-10) from baseline ranged from -2.6 to -3.3 points during the 18-week follow-up. After the first double-blind repeat treatment, a significantly higher percentage of rifaximin-treated patients were abdominal pain responders (53.9% [172/319]) vs placebo (44.4% [134/302], P = 0.02), with similar results after the second repeat treatment (52.9% [155/293] vs 44.7% [123/275], respectively, P = 0.047). A significantly higher percentage of rifaximin-treated patients were weekly abdominal pain responders for ≥50% of the 18-week double-blind repeat treatment phase (47.9% [138/288] vs 35.9% [97/270], P = 0.004). DISCUSSION Rifaximin is efficacious in improving abdominal pain in adults with IBS-D.
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Affiliation(s)
- Anthony Lembo
- Beth Israel Deaconess Medical Center, Department of Medicine, Division of Gastroenterology, Boston, Massachusetts, USA
| | - Satish S. C. Rao
- Department of Medicine, Division of Gastroenterology/Hepatology, Augusta University, Augusta, Georgia, USA
| | - Zeev Heimanson
- Salix Pharmaceuticals, Department of Medical Affairs, Bridgewater, New Jersey, USA
| | - Mark Pimentel
- Medically Associated Science and Technology Program, Cedars-Sinai Medical Center, Los Angeles, California, USA
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31
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Bowers SJ, Vargas F, González A, He S, Jiang P, Dorrestein PC, Knight R, Wright KP, Lowry CA, Fleshner M, Vitaterna MH, Turek FW. Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome. PLoS One 2020; 15:e0229001. [PMID: 32078624 PMCID: PMC7032712 DOI: 10.1371/journal.pone.0229001] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 01/27/2020] [Indexed: 02/07/2023] Open
Abstract
It has been established in recent years that the gut microbiome plays a role in health and disease, potentially via alterations in metabolites that influence host physiology. Although sleep disruption and gut dysbiosis have been associated with many of the same diseases, studies investigating the gut microbiome in the context of sleep disruption have yielded inconsistent results, and have not assessed the fecal metabolome. We exposed mice to five days of sleep disruption followed by four days of ad libitum recovery sleep, and assessed the fecal microbiome and fecal metabolome at multiple timepoints using 16S rRNA gene amplicons and untargeted LC-MS/MS mass spectrometry. We found global shifts in both the microbiome and metabolome in the sleep-disrupted group on the second day of recovery sleep, when most sleep parameters had recovered to baseline levels. We observed an increase in the Firmicutes:Bacteroidetes ratio, along with decreases in the genus Lactobacillus, phylum Actinobacteria, and genus Bifidobacterium in sleep-disrupted mice compared to control mice. The latter two taxa remained low at the fourth day post-sleep disruption. We also identified multiple classes of fecal metabolites that were differentially abundant in sleep-disrupted mice, some of which are physiologically relevant and commonly influenced by the microbiome. This included bile acids, and inference of microbial functional gene content suggested reduced levels of the microbial bile salt hydrolase gene in sleep-disrupted mice. Overall, this study adds to the evidence base linking disrupted sleep to the gut microbiome and expands it to the fecal metabolome, identifying sleep disruption-sensitive bacterial taxa and classes of metabolites that may serve as therapeutic targets to improve health after poor sleep.
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Affiliation(s)
- Samuel J. Bowers
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurobiology, Northwestern University, Evanston, Illinois, United States of America
- * E-mail:
| | - Fernando Vargas
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America
| | - Antonio González
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, United States of America
| | - Shannon He
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurobiology, Northwestern University, Evanston, Illinois, United States of America
| | - Peng Jiang
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurobiology, Northwestern University, Evanston, Illinois, United States of America
| | - Pieter C. Dorrestein
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, United States of America
| | - Rob Knight
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, United States of America
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, United States of America
| | - Kenneth P. Wright
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States of America
- Center for Neuroscience, University of Colorado Boulder, Boulder, Colorado, United States of America
- Sleep and Chronobiology Laboratory, University of Colorado Boulder, Boulder, Colorado, United States of America
| | - Christopher A. Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States of America
- Center for Neuroscience, University of Colorado Boulder, Boulder, Colorado, United States of America
| | - Monika Fleshner
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States of America
- Center for Neuroscience, University of Colorado Boulder, Boulder, Colorado, United States of America
| | - Martha H. Vitaterna
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurobiology, Northwestern University, Evanston, Illinois, United States of America
| | - Fred W. Turek
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurobiology, Northwestern University, Evanston, Illinois, United States of America
- The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
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Mazzawi T, Eikrem Ø, Lied GA, Hausken T. Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation. Gastroenterol Res Pract 2020; 2020:3520686. [PMID: 32089675 PMCID: PMC7024100 DOI: 10.1155/2020/3520686] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 12/17/2019] [Accepted: 01/07/2020] [Indexed: 12/18/2022] Open
Abstract
Altered densities of enteroendocrine cells play an important role in patients with irritable bowel syndrome (IBS). Uroguanylin activates guanylate cyclase-C to regulate intestinal electrolyte and water transport. Aim. To quantify uroguanylin immunoreactive cells density in the duodenum of diarrhea-predominant IBS (IBS-D) patients compared to controls and to investigate the effect of fecal microbiota transplantation (FMT) on these cell densities. Method. Twelve patients with IBS-D according to Rome III criteria were included. The cause was identified as post infectious (PI, n = 6) or idiopathic (n = 6). They completed the IBS-symptom questionnaire before and 3 weeks after FMT. Thirty grams of fresh feces donated from healthy relatives were diluted with 60 ml normal saline and instilled via endoscope into the duodenum. Biopsies were taken from the patients' duodenum before and 3 weeks after FMT. Duodenal biopsies taken from eight healthy controls were also included. The biopsies were immunostained for uroguanylin and quantified using computerized image analysis. Results. Uroguanylin immunoreactive cells were found both in duodenal villi and crypts in both controls and IBS-D patients. The densities of uroguanylin immunoreactive cells were significantly lower in the villi (P < 0.0001) and higher in the crypts (P < 0.0001) for the patients than the controls. Following FMT, the densities of uroguanylin immunoreactive cells for the total group and idiopathic subgroup decreased significantly in the duodenal crypts (P = 0.049 and 0.04, respectively) but not in the villi. No significant changes were shown in the PI-IBS subgroups. The cells density in only the crypts correlated with diarrhea (r = 0.97, P = 0.001) and bloating (r = -0.91, P = 0.01) in the PI-IBS subgroup before FMT and with abdominal pain (r = 0.63, P = 0.03) in the total group of IBS-D patients after FMT. Conclusion. Altered uroguanylin immunoreactive cells density was found in IBS-D patients compared to controls. Changes in these cells density following FMT correlated with IBS symptoms (diarrhea, bloating, and abdominal pain).
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Affiliation(s)
- Tarek Mazzawi
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Øystein Eikrem
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Gülen Arslan Lied
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Trygve Hausken
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Wang Y, Zheng F, Liu S, Luo H. Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome. Gastroenterol Res Pract 2019; 2019:9759138. [PMID: 31885549 PMCID: PMC6914991 DOI: 10.1155/2019/9759138] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 09/10/2019] [Accepted: 11/07/2019] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.
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Affiliation(s)
- Yao Wang
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Fengling Zheng
- The Journal Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Shan Liu
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Huanhuan Luo
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
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D'Haens GR, Jobin C. Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection. Gastroenterology 2019; 157:624-636. [PMID: 31220424 PMCID: PMC7179251 DOI: 10.1053/j.gastro.2019.04.053] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Revised: 04/15/2019] [Accepted: 04/20/2019] [Indexed: 02/08/2023]
Abstract
As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in the development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of fecal microbiota transplantation. We discuss opportunities for treatment of other diseases with fecal microbiota transplantation, based on findings from small clinical and preclinical studies.
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Affiliation(s)
- Geert R D'Haens
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Christian Jobin
- Departments of Medicine, Anatomy and Cell Biology, and Infectious Diseases and Immunology, University of Florida, Gainesville, Florida.
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Huang HL, Chen HT, Luo QL, Xu HM, He J, Li YQ, Zhou YL, Yao F, Nie YQ, Zhou YJ. Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. J Dig Dis 2019; 20:401-408. [PMID: 31070838 DOI: 10.1111/1751-2980.12756] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 04/17/2019] [Accepted: 05/06/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS). METHODS Microbiota suspensions from feces of the donors were injected into the intestines of 30 Chinese patients with refractory IBS. Microbiota composition analysis and genomic DNA extraction of fecal samples obtained from these patients at baseline and 1 month after FMT were performed. Clinical efficacy and safety of FMT were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up. RESULTS FMT improved IBS gastrointestinal symptoms and alleviated depression and anxiety, as shown by the improved IBS-QOL, IBS-SSS, GSRS, HAMA and HAMD scores at 1 month and 3 months after FMT. A total adverse event rate of FMT was 6.7% (2/30). Gut microbiota analysis revealed that FMT responders had a significantly higher Shannon diversity index before FMT than non-responders. In addition, analysis of differences in bacterial composition before and after FMT in responders showed specific abundance of the phyla Verrucomincrobia and Euryarchaeota at 1 month after FMT. At the genus level, Methanobrevibacter and Akkermansia were the most abundant fecal microbiota 1 month after FMT compared with those before FMT. CONCLUSIONS FMT may be an effective and safe therapeutic strategy for treating IBS that achieves a sustained clinical response 3-6 months after the first procedure. Changes in the diversity and dominant flora may contribute to its therapeutic effect.
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Affiliation(s)
- Hong Li Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hui Ting Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Qing Ling Luo
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hao Ming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yong Qiang Li
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - You Lian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Fei Yao
- Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Yu Qiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yong Jian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
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El-Salhy M, Hausken T, Hatlebakk JG. Increasing the Dose and/or Repeating Faecal Microbiota Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS). Nutrients 2019; 11:E1415. [PMID: 31238507 PMCID: PMC6628324 DOI: 10.3390/nu11061415] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 06/19/2019] [Accepted: 06/21/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Faecal microbiome transplantation (FMT) appears to be an effective method for treating irritable bowel syndrome (IBS) patients. However, it is not clear if a high transplant dose and/or repeating FMT are/is needed to ensure a response. The present study was undertaken to clarify this matter. METHODS Ten IBS patients who did not respond to a 30-g transplant subsequently received a 60-g transplant into the duodenum via a gastroscope. The patients provided faecal samples before and 1 month after FMT. They completed five questionnaires measuring symptoms, fatigue and quality of life at baseline and then at 2 weeks, 1 month and 3 months after FMT. The dysbiosis index (DI) was measured using the GA-map Dysbiosis Test®. RESULTS Seven patients (70%) responded to the 60-g transplant, with significant clinical improvements in the abdominal symptoms, fatigue and quality of life in 57%, 80% and 67% of these patients. The 60-g transplant also reduced the DI. CONCLUSION FMT is an effective treatment for IBS. A high-dose transplant and/or repeated FMT increase the response rate and the intensity of the effects of FMT.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Box 4000, 54 09 Stord, Norway.
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
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Maillard F, Vazeille E, Sauvanet P, Sirvent P, Combaret L, Sourdrille A, Chavanelle V, Bonnet R, Otero YF, Delcros G, Barnich N, Boisseau N. High intensity interval training promotes total and visceral fat mass loss in obese Zucker rats without modulating gut microbiota. PLoS One 2019; 14:e0214660. [PMID: 30964881 PMCID: PMC6456220 DOI: 10.1371/journal.pone.0214660] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 03/19/2019] [Indexed: 12/13/2022] Open
Abstract
Aims Increased visceral adipose tissue and dysbiosis in the overweight and obese promote chronic inflammation. The aim of this study was to compare the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on the gut-adipose tissue cross-talk in obese Zucker rats. Methods Obese male Zucker rats (n = 36) were divided in three groups: MICT (12m.min-1 for 51min), HIIT (6 sets at 18 m.min-1 for 4min followed by 3min at 10m.min-1) and controls (CONT; no exercise). The animals ran on a treadmill 5 days/week for 10 weeks. Body composition, glycaemic control, lipid profile, inflammation, lipolysis signalling in subcutaneous and visceral adipose tissue, intestinal permeability (tight junctions and plasma lipopolysaccharide binding protein; LBP), and gut microbiota composition were assessed in the three groups. Results After 10 weeks of exercise, total and epididymal fat mass decreased only in the HIIT group. The α/β adrenergic receptor RNA ratio in subcutaneous adipose tissue increased only in the HIIT group. The expression level of phosphorylated hormone-sensitive lipase was not modified by training. Both HIIT and MICT decreased inflammation (plasma myeloperoxidase and keratinocyte-derived chemokine secretion in adipose tissue) and improved glucose metabolism. Zonula occludens-1 and occludin were upregulated in the HIIT group. Plasma LBP was similarly reduced in both training groups. HIIT and MICT did not affect gut microbiota composition. Conclusion In obese Zucker rats, HIIT and MICT improved inflammation and glucose metabolism. In contrast, only HIIT decreased total and visceral fat mass. These adaptations were not associated with modifications in gut microbiota composition.
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Affiliation(s)
- Florie Maillard
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
- Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France
- * E-mail:
| | - Emilie Vazeille
- Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d’Hépato-Gastro Entérologie, Clermont-Ferrand, France
| | - Pierre Sauvanet
- Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France
- Université Clermont Auvergne, CHU Clermont-Ferrand, Service de chirurgie digestive, Clermont-Ferrand, France
| | - Pascal Sirvent
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
| | - Lydie Combaret
- Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, Clermont-Ferrand, France
| | - Antoine Sourdrille
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
| | - Vivien Chavanelle
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
| | - Richard Bonnet
- Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France
- Department of Bacteriology, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Yolanda Fernandez Otero
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
| | - Geoffrey Delcros
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
| | - Nicolas Barnich
- Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France
| | - Nathalie Boisseau
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Clermont-Ferrand, France
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Szymaszkiewicz A, Storr M, Fichna J, Zielinska M. Enkephalinase inhibitors, potential therapeutics for the future treatment of diarrhea predominant functional gastrointestinal disorders. Neurogastroenterol Motil 2019; 31:e13526. [PMID: 30549162 DOI: 10.1111/nmo.13526] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/20/2018] [Accepted: 11/12/2018] [Indexed: 02/08/2023]
Abstract
The endogenous opioid system (EOS) is considered being a crucial element involved in the pathophysiology of irritable bowel syndrome (IBS) as it regulates gastrointestinal (GI) homeostasis through modulation of motility and water and ion secretion/absorption. Along with opioid receptors (ORs), the following components of EOS can be distinguished: 1. endogenous opioid peptides (EOPs), namely enkephalins, endorphins, endomorphins and dynorphins, and 2. peptidases, which regulate the metabolism (synthesis and degradation) of EOPs. Enkephalins, which are δ-opioid receptors agonists, induce significant effects in the GI tract as they act as potent pro-absorptive neurotransmitters. The action of enkephalins and other EOPs is limited, since EOPs are easily and rapidly inactivated by a natural metalloendopeptidase (enkephalinase/neprilysin) and aminopeptidase N. Studies show that the activity of EOPs can be enhanced by inhibition of these enzymes. In this review, we discuss the antidiarrheal and antinociceptive potential of enkephalinase inhibitors. Furthermore, our review is to answer the question whether enkephalinase inhibitors may be helpful in the future treatment of diarrhea predominant functional GI disorders.
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Affiliation(s)
- Agata Szymaszkiewicz
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Martin Storr
- Department of Medicine, Ludwig Maximilians University Munich, Munich, Germany.,Center of Endoscopy, Starnberg, Germany
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Marta Zielinska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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Nielsen ES, Garnås E, Jensen KJ, Hansen LH, Olsen PS, Ritz C, Krych L, Nielsen DS. Lacto-fermented sauerkraut improves symptoms in IBS patients independent of product pasteurisation - a pilot study. Food Funct 2019; 9:5323-5335. [PMID: 30256365 DOI: 10.1039/c8fo00968f] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Lacto-fermented sauerkraut contains a natural variety of lactic acid bacteria (LAB) and has not previously been studied in the treatment of irritable bowel syndrome (IBS) patients. The present study investigated the effect of a daily lacto-fermented sauerkraut supplement in relation to IBS patients' gastrointestinal symptoms and gut microbiota composition. A randomized double-blinded intervention was conducted with 34 Norwegian IBS patients. The patients were consuming either pasteurized sauerkraut (PS; n = 15) or unpasteurized sauerkraut (UPS; n = 19) as a supplement to their daily diet for 6 weeks. The differences in change of symptoms were assessed using the questionnaire IBS-Symptom Severity Score (IBS-SSS) measured at the baseline, and at weeks 2, 4, 6 and 8 (follow-up). The gut microbiota composition was analysed using 16S rRNA gene amplicon sequencing of faecal samples from the baseline and week 6. The mean change in IBS-SSS was -38.57 ± 17.08 PS vs. -56.99 ± 16.92 UPS and was significantly improved in both groups (P < 0.04), while the improvement in symptoms was not different between the intervention groups. The sauerkraut intervention (pasteurized or not) also led to significant gut microbiota compositional changes as determined by 16S rRNA gene amplicon sequencing (un-weighted UniFrac: P = 0.001, weighted UniFrac: P = 0.001). Sauerkraut related LAB in feces (Lactobacillus plantarum and Lactobacillus brevis) were significantly more often present in the UPS-group. In conclusion lacto-fermented sauerkraut had an effect on IBS patients' symptoms and gut microbiota even though the study was underpowered. Our results indicate that the observed effect to a larger extent can be attributed to the potential prebiotics in lacto-fermented sauerkraut rather than the viable LAB. Future studies with greater statistical power are needed to clarify the possible effects of LAB from lacto-fermented sauerkraut in the treatment of IBS patients.
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40
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Yin B, Song Q, Chen L, Li X, Han Y, Wang X, Dai J, Sun X. Establishment of an immortalized intestinal epithelial cell line from tree shrews by lentivirus-mediated hTERT gene transduction. Cytotechnology 2019; 71:107-116. [PMID: 30603916 PMCID: PMC6368523 DOI: 10.1007/s10616-018-0270-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 10/16/2018] [Indexed: 11/28/2022] Open
Abstract
The intestinal epithelium has an average lifespan of 4–5 days. Normally, primary intestinal epithelial cells can be cultured for about 15 days in vitro. The aim of this study was to explore methods to isolate and immortalize intestinal epithelial cells (IECs) of tree shrews in order to establish a new resource of experimental material and to provide a cell model for drug development and infection mechanism research. Tissue from the small intestine of tree shrews was digested with collagenase XI, neutral protease I, and dithiothreitol. The human telomerase reverse transcriptase gene (hTERT) was transferred into tree shrew IECs using the pHBLV-CMVIE-ZsGreen-Puro vector. The level of hTERT mRNA was detected by quantitative reverse transcription polymerase chain reaction. Immunofluorescence and western blot assays were performed to detect biochemical markers of IECs. The micromorphology of cells was observed with electron microscopy. We then conducted experiments to assess proliferative activity and analyze the karyotype of isolated cells. The results showed the immortalized cell line that we established and screened, maintained the characteristics and biochemical markers of primary IECs. Our results showed that the cell line we established can be considered an alternative cell model for intestinal drug research and for studies on intestinal infection and cell signaling.
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Affiliation(s)
- Bowen Yin
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China.
| | - Qingkai Song
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Lingxia Chen
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Xiaofei Li
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Yuanyuan Han
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Xuan Wang
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Jiejie Dai
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China
| | - Xiaomei Sun
- Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science, Peking Union Medical College, Jiaoling Road 935, Kunming, 650118, China.
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Carstens A, Roos A, Andreasson A, Magnuson A, Agréus L, Halfvarson J, Engstrand L. Differential clustering of fecal and mucosa-associated microbiota in 'healthy' individuals. J Dig Dis 2018; 19:745-752. [PMID: 30467977 DOI: 10.1111/1751-2980.12688] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 10/31/2018] [Accepted: 11/19/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Fecal samples are often used to characterize gut microbiota. However, whether or not fecal microbiota differs from mucosa-associated microbiota remains largely unknown. This may be specifically relevant in conditions that are characterized by complex mucosal microbe-host interactions, such as Crohn's disease. We aimed to determine the degree of agreement between fecal and mucosal microbiota profiles in 'healthy' individuals, using two commonly used collection procedures. METHODS The gut microbiota composition of fecal samples (sent at ambient temperature before storage at -70°C) and of colonic biopsies (obtained at endoscopy and immediately stored at -70°C) was determined by sequencing the 16S rRNA gene. Altogether 31 randomly selected 'healthy' individuals from the population-based colonoscopy (Popcol) study were included. RESULTS The fecal samples were characterized by a reduced degree of richness (P < 0.0001) and diversity (P = 0.016), and also differences in several phyla, including a lower relative abundance of Proteobacteria (P < 0.0001) and Verrucomicrobia (P = 0.008) than in biopsies. Only three of 30 individuals had a similar fecal and mucosal microbiota profile, based on weighted UniFrac analysis. A difference in Crohn's disease dysbiosis-associated bacteria was observed, including a lower relative abundance of Faecalibacterium (P = 0.004) and a higher relative abundance of Ruminococcus (P = 0.001) in feces than in biopsies. CONCLUSIONS The observed differences between fecal samples, transported at ambient temperature, and the colonic mucosa-associated microbiota have implications for the interpretation of the previous literature, and may be specifically relevant to studies on Crohn's disease.
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Affiliation(s)
- Adam Carstens
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Department of Internal Medicine, Ersta Hospital, Stockholm, Sweden
| | - Annika Roos
- Department of Microbiology, Tumor and Cell Biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden
| | - Anna Andreasson
- Department of Microbiology, Tumor and Cell Biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden.,Division for Family Medicine, Karolinska Institute, Stockholm, Sweden.,Stress Research Institute, Stockholm University, Stockholm, Sweden
| | - Anders Magnuson
- Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Lars Agréus
- Division for Family Medicine, Karolinska Institute, Stockholm, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden
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42
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Chen YJ, Wu H, Wu SD, Lu N, Wang YT, Liu HN, Dong L, Liu TT, Shen XZ. Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation. J Gastroenterol Hepatol 2018; 33:1844-1852. [PMID: 29744928 DOI: 10.1111/jgh.14281] [Citation(s) in RCA: 197] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 03/29/2018] [Accepted: 04/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS. METHODS Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology. RESULTS Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS. CONCLUSION Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.
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Affiliation(s)
- Yan-Jie Chen
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Hao Wu
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Sheng-Di Wu
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Nan Lu
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yi-Ting Wang
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Hai-Ning Liu
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Ling Dong
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Tao-Tao Liu
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Xi-Zhong Shen
- Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China
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43
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Wen W, Zhang H, Shen J, Wei L, Shen S. Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol. Medicine (Baltimore) 2018; 97:e12661. [PMID: 30290648 PMCID: PMC6200478 DOI: 10.1097/md.0000000000012661] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 09/13/2018] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.
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Barajas-Nava LA, Consuelo Sánchez A, Castilla-Peon MF, Pizarro-Castellanos MP, Vazquez Frias R. Probiotics for the treatment of irritable bowel syndrome in children. Hippokratia 2018. [DOI: 10.1002/14651858.cd013095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Leticia A Barajas-Nava
- Hospital Infantil de México Federico Gómez (HIMFG), Health National Institute; Evidence-Based Medicine Research Unit; Dr. Márquez #162 Col. Doctores, Del. Cuauhtémoc México City Mexico 06720
| | - Alejandra Consuelo Sánchez
- Hospital Infantil de México Federico Gómez; Pediatric Gastroenterology and Nutrition; Dr. Marquez 162, Doctores, Cuauhtémoc Mexico City Mexico ZP 06720
| | | | | | - Rodrigo Vazquez Frias
- Hospital Infantil de México Federico Gómez; Pediatric Gastroenterology and Nutrition; Dr. Marquez 162, Doctores, Cuauhtémoc Mexico City Mexico ZP 06720
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Fukui H, Xu X, Miwa H. Role of Gut Microbiota-Gut Hormone Axis in the Pathophysiology of Functional Gastrointestinal Disorders. J Neurogastroenterol Motil 2018; 24:367-386. [PMID: 29969855 PMCID: PMC6034676 DOI: 10.5056/jnm18071] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 05/21/2018] [Indexed: 12/13/2022] Open
Abstract
Gut microbiota exert a pivotal influence on various functions including gastrointestinal (GI) motility, metabolism, nutrition, immunity, and the neuroendocrine system in the host. These effects are mediated by not only short-chain fatty acids produced by microbiota but also gut hormones and inflammatory signaling by enteroendocrine and immune cells under the influence of the microbiota. GI motility is orchestrated by the enteric nervous system and hormonal networks, and disturbance of GI motility plays an important role in the pathophysiology of functional gastrointestinal disorders (FGIDs). In this context, microbiota-associated mediators are considered to act on specific receptors, thus affecting the enteric nervous system and, subsequently, GI motility. Thus, the pathophysiology of FGIDs is based on alterations of the gut microbiota/gut hormone axis, which have crucial effects on GI motility.
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Affiliation(s)
- Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa, Nishinomiya,
Japan
| | - Xin Xu
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa, Nishinomiya,
Japan
- Department of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin,
China
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa, Nishinomiya,
Japan
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46
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Geerlings SY, Kostopoulos I, de Vos WM, Belzer C. Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How? Microorganisms 2018; 6:microorganisms6030075. [PMID: 30041463 PMCID: PMC6163243 DOI: 10.3390/microorganisms6030075] [Citation(s) in RCA: 278] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/03/2018] [Accepted: 07/12/2018] [Indexed: 02/06/2023] Open
Abstract
Akkermansia muciniphila is a mucin-degrading bacterium of the phylum Verrucomicrobia. Its abundance in the human intestinal tract is inversely correlated to several disease states. A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity. We explore the presence of Akkermansia-like spp. based on its 16S rRNA sequence and metagenomic signatures in the human body so as to understand its colonization pattern in time and space. A. muciniphila signatures were detected in colonic samples as early as a few weeks after birth and likely could be maintained throughout life. The sites where Akkermansia-like sequences (including Verrucomicrobia phylum and/or Akkermansia spp. sequences found in the literature) were detected apart from the colon included human milk, the oral cavity, the pancreas, the biliary system, the small intestine, and the appendix. The function of Akkermansia-like spp. in these sites may differ from that in the mucosal layer of the colon. A. muciniphila present in the appendix or in human milk could play a role in the re-colonization of the colon or breast-fed infants, respectively. In conclusion, even though A. muciniphila is most abundantly present in the colon, the presence of Akkermansia-like spp. along the digestive tract indicates that this bacterium might have more functions than those currently known.
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Affiliation(s)
- Sharon Y Geerlings
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, 6708WE Wageningen, The Netherlands.
| | - Ioannis Kostopoulos
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, 6708WE Wageningen, The Netherlands.
| | - Willem M de Vos
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, 6708WE Wageningen, The Netherlands.
- Immunobiology Research Program, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, 6708WE Wageningen, The Netherlands.
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Fodor AA, Pimentel M, Chey WD, Lembo A, Golden PL, Israel RJ, Carroll IM. Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome. Gut Microbes 2018; 10:22-33. [PMID: 29708822 PMCID: PMC6363070 DOI: 10.1080/19490976.2018.1460013] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/28/2018] [Accepted: 03/28/2018] [Indexed: 02/03/2023] Open
Abstract
Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.
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Affiliation(s)
- Anthony A. Fodor
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, USA
| | - Mark Pimentel
- Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - William D. Chey
- Division of Gastroenterology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Anthony Lembo
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Pamela L. Golden
- Nonclinical and Clinical Pharmacology, Clinical and Medical Affairs, Salix Pharmaceuticals, Bridgewater, New Jersey, USA**
| | - Robert J. Israel
- Nonclinical and Clinical Pharmacology, Clinical and Medical Affairs, Salix Pharmaceuticals, Bridgewater, New Jersey, USA**
| | - Ian M. Carroll
- Department of Nutrition and Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
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Maharshak N, Ringel Y, Katibian D, Lundqvist A, Sartor RB, Carroll IM, Ringel-Kulka T. Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Dig Dis Sci 2018; 63:1890-1899. [PMID: 29777439 DOI: 10.1007/s10620-018-5086-4] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 04/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC). AIMS To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC. METHODS The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline. RESULTS The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche. CONCLUSION Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.
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Affiliation(s)
- Nitsan Maharshak
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA
- Bacteriotherapy Clinic, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv, Israel
| | - Yehuda Ringel
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA.
- Department of Gastroenterology and Hepatology, Meir Medical Center, Affiliated with Tel Aviv University, 59 Tshernichovsky St., 4428164, Kfar Saba, Israel.
| | - David Katibian
- Bacteriotherapy Clinic, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv, Israel
| | - Ashley Lundqvist
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA
| | - R Balfour Sartor
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7309A MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA
| | - Ian M Carroll
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA
| | - Tamar Ringel-Kulka
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 404A Rosenau, Chapel Hill, NC, 27599, USA
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Li G, Yang M, Jin Y, Li Y, Qian W, Xiong H, Song J, Hou X. Involvement of shared mucosal-associated microbiota in the duodenum and rectum in diarrhea-predominant irritable bowel syndrome. J Gastroenterol Hepatol 2018; 33:1220-1226. [PMID: 29194775 DOI: 10.1111/jgh.14059] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 11/11/2017] [Accepted: 11/23/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Most studies of diarrhea-predominant irritable bowel syndrome (IBS-D) focused on microbiota dysbiosis in a single segment of the intestine such as the colon. However, the intestine as a whole is involved in IBS-D and knowledge about the role of microbiota shared by the duodenum and rectum in IBS-D is limited. Here, we investigated the characteristics of mucosal microbiota shared by the duodenum and rectum in IBS-D patients. METHODS We collected duodenal and rectal mucosal samples from 33 adult IBS-D patients and 15 healthy control (HC) subjects. The 454 pyrosequencing method and multiple bioinformatics analyses were used to examine bacterial 16S rRNA. Clinical data including symptoms and Bristol Stool Form were analyzed. RESULTS Mucosal microbiota in duodenal samples differed from rectal samples in HC, while less difference was shown in IBS-D. More numbers in terms of shared operational taxonomic units and genera found in IBS-D compared with HC. The frequency of genera in the duodenum and rectum of HC differed from that of IBS-D. We identified 24 genera shared in the duodenum and rectum, which both changed dramatically in IBS-D. Among these 24 genera, half had similar trends in frequency differences, and the other half had opposite trends. The frequency of Faecalibacterium and Hyphomicrobium were associated with clinical data of IBS-D patients. CONCLUSIONS Shared mucosal-associated microbiota in the duodenum and rectum appear to contribute to the etiology and pathophysiology of whole intestine of IBS-D and to be potential therapeutic targets.
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Affiliation(s)
- Gangping Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Jin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Qian
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanhua Xiong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Ford AC, Moayyedi P, Chey WD, Harris LA, Lacy BE, Saito YA, Quigley EMM. American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome. Am J Gastroenterol 2018; 113:1-18. [PMID: 29950604 DOI: 10.1038/s41395-018-0084-x] [Citation(s) in RCA: 232] [Impact Index Per Article: 33.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Alexander C Ford
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds and Leeds Gastroenterology Institute, Leeds Teaching Hospitals Trust, Leeds, UK
| | - Paul Moayyedi
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - William D Chey
- Division of Gastroenterology, Department of Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | | | | | | | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA.
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