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Barbara G, Aziz I, Ballou S, Chang L, Ford AC, Fukudo S, Nurko S, Olano C, Saps M, Sayuk G, Siah KTH, Van Oudenhove L, Simrén M. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol 2025; 22:228-251. [PMID: 39870943 DOI: 10.1038/s41575-024-01033-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Sarah Ballou
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Shin Fukudo
- Department of Psychosomatic Medicine, Japanese Red Cross Ishinomaki Hospital, Research Center for Accelerator and Radioisotope Science, Tohoku University, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Samuel Nurko
- Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA, USA
| | - Carolina Olano
- Gastroenterology Department. Universidad de la República, Montevideo, Uruguay
| | - Miguel Saps
- Division of Gastroenterology, Hepatology, and Nutrition, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Gregory Sayuk
- Gastroenterology Division, Washington University School of Medicine, St. Louis, MO, USA
- St. Louis Veterans Affairs Medical Center, St. Louis, MO, USA
| | - Kewin T H Siah
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
- Consultation-Liaison Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Gweon TG, Kang SB, Na SY, Oh DJ, Kim SW, Seo GS, Cho JY. Five-Day Treatment with B. licheniformis Along with Classical Vancomycin Treatment Was Effective in Preserving Gut Microbiota in Patients with Clostridioides difficile Infection. Nutrients 2025; 17:641. [PMID: 40004971 PMCID: PMC11858508 DOI: 10.3390/nu17040641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/06/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives:Clostridioides difficile infection (CDI) is an important nosocomial diarrheal disease. The benefits of the probiotic Bacillus licheniformis (B. licheniformis) in the preservation of intestinal microbiota have not been studied in patients with CDI to date. Therefore, we aimed to investigate the efficacy of B. licheniformis in preserving the intestinal microbiota in patients with CDI. Methods: A multicenter, randomized, placebo-controlled trial was carried out at six academic centers in Korea. Individuals diagnosed with mild to moderate CDI were included in this trial. CDI was treated with vancomycin 125 mg four times daily for two weeks. Along with vancomycin, B. licheniformis was administered for five days in this study, while a placebo was given to the placebo group. Microbiome analysis was performed before and five days after administering vancomycin and B. licheniformis or placebo, using 16S rRNA amplicon sequencing. Alpha and beta diversity was compared between the two groups. Results: A total of 35 participants were finally included in this study, with 16 in the study group and 19 in the placebo group. The alpha diversity was similar in both groups before CDI treatment. After five days of the administration of vancomycin and B. licheniformis or placebo, alpha diversity did not decrease in the study group (Chao1 index, p = 0.665; observed features, p = 0.692). In contrast, alpha diversity decreased in the placebo group (Chao1 index, p = 0.011; observed features, p = 0.011). Beta diversity did not differ between the two groups. Conclusions: The addition of B. licheniformis to vancomycin was effective in preserving gut microbiota in patients with CDI.
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Affiliation(s)
- Tae-Geun Gweon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 02812, Republic of Korea; (T.-G.G.); (S.-B.K.); (S.-Y.N.)
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14662, Republic of Korea
| | - Sang-Bum Kang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 02812, Republic of Korea; (T.-G.G.); (S.-B.K.); (S.-Y.N.)
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Republic of Korea
| | - Soo-Young Na
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 02812, Republic of Korea; (T.-G.G.); (S.-B.K.); (S.-Y.N.)
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea
| | - Dong Jun Oh
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea;
| | - Sang Wook Kim
- Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea;
| | - Geom Seog Seo
- Department of Internal Medicine, Digestive Disease Research Institute, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - Joo Young Cho
- Department of Internal Medicine, Cha Medical Center Gangnam, Seoul 06135, Republic of Korea
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Taghaddos D, Saqib Z, Bai X, Bercik P, Collins SM. Post-infectious ibs following Clostridioides difficile infection; role of microbiota and implications for treatment. Dig Liver Dis 2024; 56:1805-1809. [PMID: 38653643 DOI: 10.1016/j.dld.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/21/2024] [Accepted: 03/13/2024] [Indexed: 04/25/2024]
Abstract
Up to 25% of patients recovering from antibiotic-treated Clostridioides difficile infection (CDI) develop functional symptoms reminiscent of Post-Infectious Irritable Bowel Syndrome (PI-IBS). For patients with persistent symptoms following infection, a clinical dilemma arises as to whether to provide additional antibiotic treatment or to adopt a conservative symptom-based approach. Here, we review the literature on CDI-related PI-IBS and compare the findings with PI-IBS. We review proposed mechanisms, including the role of C. difficile toxins and the microbiota, and discuss implications for therapy. We suggest that gut dysfunction post-CDI may be initiated by toxin-induced damage to enteroglial cells and that a dysbiotic gut microbitota maintains the clinical phenotype over time, prompting consideration of microbiota-directed therapies. While Fecal Microbial Transplant (FMT) is currently reserved for recurrent CDI (rCDI), we propose that microbiota-directed therapies may have a role in primary CDI in order to avoid or mitigate futher antibiotic treatment that further disrupts the microbiota and thus prevent PI-IBS. We discuss novel microbial transfer therapies and as they emerge, we recommend clinical trials to determine whether microbial transfer therapy of the primary infection prevents both rCDI and CDI-related PI- IBS.
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Affiliation(s)
- Dana Taghaddos
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Zarwa Saqib
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Xiaopeng Bai
- Division of Gastroenterology, Kyushu University, Japan
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
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Chen Y, Wang R, Li X, Wang Z, Cao B, Du J, Deng T, Han J, Yang M. Progress of research on the treatment of depression by traditional Chinese medicine prescriptions. Heliyon 2024; 10:e34970. [PMID: 39157399 PMCID: PMC11328063 DOI: 10.1016/j.heliyon.2024.e34970] [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: 04/06/2024] [Revised: 07/03/2024] [Accepted: 07/19/2024] [Indexed: 08/20/2024] Open
Abstract
Depression is a common psychiatric disorder that belongs to the category of "Depression Syndrome" in traditional Chinese medicine (TCM), and its etiology and pathogenesis are complex and unclear. It is characterized by high prevalence, high disability rate, and high recurrence rate, which seriously affect human health, and its treatment has become a research hotspot worldwide. At present, the antidepressants commonly used in the clinic are mainly Western medicine (WM), but there are problems such as frequent side effects and poor efficacy. Studies have found that the use of TCM prescriptions in the treatment of depression can achieve the same effect as WM; and when TCM prescriptions are combined with WM, the efficacy can be enhanced while the adverse effects of WM can be reduced. Pharmacological studies related to the treatment of depression with traditional Chinese medicine prescriptions (TCMPs) have focused on the neurobiochemical system, gut microbes, and energy metabolism in mitochondria. No one has yet reviewed the pharmacological mechanism of TCMPs for depression. So, this paper reviews the pharmacological mechanism of TCMPs for depression from the perspective of TCMPs, introduces the progress of research on classical TCMPs for depression and their antidepressant mechanism. This article aims to promote the application of TCMPs in the clinic and provide a new therapeutic idea for the clinical treatment of depression.
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Affiliation(s)
- Yiwei Chen
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Ruyu Wang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Xue Li
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Zhiying Wang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Baorui Cao
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jinxin Du
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Tingting Deng
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jinxiang Han
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Meina Yang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
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Gryaznova M, Smirnova Y, Burakova I, Morozova P, Lagutina S, Chizhkov P, Korneeva O, Syromyatnikov M. Fecal Microbiota Characteristics in Constipation-Predominant and Mixed-Type Irritable Bowel Syndrome. Microorganisms 2024; 12:1414. [PMID: 39065182 PMCID: PMC11278693 DOI: 10.3390/microorganisms12071414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common condition that affects the lifestyle of patients. It is associated with significant changes in the composition of the gut microbiome, but the underlying microbial mechanisms remain to be fully understood. We study the fecal microbiome of patients with constipation-predominant IBS (IBS-C) and mixed-type IBS (IBS-M). METHODS We sequenced the V3 region of the 16S rRNA on the Ion Torrent PGM sequencing platform to study the microbiome. RESULTS In the patients with IBS-C and IBS-M, an increase in alpha diversity was found, compared to the healthy group, and differences in beta diversity were also noted. At the phylum level, both IBS subtypes showed an increase in the Firmicutes/Bacteroidetes ratio, as well as an increase in the abundance of Actinobacteria and Verrucomicrobiota. Changes in some types of bacteria were characteristic of only one of the IBS subtypes, while no statistically significant differences in the composition of the microbiome were detected between IBS-C and IBS-M. CONCLUSIONS This study was the first to demonstrate the association of Turicibacter sanguinis, Mitsuokella jalaludinii, Erysipelotrichaceae UCG-003, Senegalimassilia anaerobia, Corynebacterium jeikeium, Bacteroides faecichinchillae, Leuconostoc carnosum, and Parabacteroides merdae with IBS subtypes.
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Affiliation(s)
- Mariya Gryaznova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Yuliya Smirnova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Inna Burakova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Polina Morozova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
| | - Svetlana Lagutina
- Department of Polyclinic Therapy, Voronezh State Medical University Named after N.N. Burdenko, 394036 Voronezh, Russia;
| | - Pavel Chizhkov
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
| | - Olga Korneeva
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Mikhail Syromyatnikov
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
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Gaus OV, Livzan MA, Gavrilenko DA. Risk factors for irritable bowel syndrome: A review. TERAPEVT ARKH 2024; 96:159-167. [DOI: 10.26442/00403660.2024.02.202597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Irritable bowel syndrome (IBS) is one of the most common diseases of the digestive tract from the group of disorders of interaction in the gut-brain axis. IBS has a negative impact of on patients' quality of life and the significant social and economic burden of the disease due to the low effectiveness of available treatment strategies, which are only symptomatic, without impacting factors and mechanisms of intestinal dysfunction. From this perspective, it is critical to study the factors contributing to the onset and persistence of IBS symptoms to improve the early diagnosis of the disease and implement targeted prevention technology in at-risk groups. The objective of this paper is to systematize data on the main risk factors for IBS, including hereditary predisposition, stress and psycho-emotional state, diet and eating habits, and acute intestinal infections.
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Šojat D, Volarić M, Keškić T, Volarić N, Cerovečki V, Trtica Majnarić L. Putting Functional Gastrointestinal Disorders within the Spectrum of Inflammatory Disorders Can Improve Classification and Diagnostics of These Disorders. Biomedicines 2024; 12:702. [PMID: 38540315 PMCID: PMC10967747 DOI: 10.3390/biomedicines12030702] [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: 03/01/2024] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 01/03/2025] Open
Abstract
The spectrum, intensity, and overlap of symptoms between functional gastrointestinal disorders (FGIDs) and other gastrointestinal disorders characterize patients with FGIDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis of FGID and the applicability of a given treatment is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found to cause the continuous existence of a low level of inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and the intestinal functions, including the involvement of gut bacteria. In this review paper, we intend to promote the hypothesis that FGIDs should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic, and microbiome pathways. This hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, that is omnipresent in chronic health conditions. A better understanding of inflammation's role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs may reduce patient heterogeneity and help clarify the pathophysiology of this disease to allow for better treatment.
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Affiliation(s)
- Dunja Šojat
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
| | - Mile Volarić
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
- Department of Gastroenterology and Hepatology, University Clinical Hospital Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina
| | - Tanja Keškić
- Department Biomedicine, Technology and Food Safety, Laboratory of Chemistry and Microbiology, Institute for Animal Husbandry, Autoput Belgrade-Zagreb 16, 11080 Belgrade, Serbia;
| | - Nikola Volarić
- Department of Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena ulica 21, 31000 Osijek, Croatia;
| | - Venija Cerovečki
- Department of Family Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia;
| | - Ljiljana Trtica Majnarić
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
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Kraimi N, Ross T, Pujo J, De Palma G. The gut microbiome in disorders of gut-brain interaction. Gut Microbes 2024; 16:2360233. [PMID: 38949979 PMCID: PMC11218806 DOI: 10.1080/19490976.2024.2360233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 05/21/2024] [Indexed: 07/03/2024] Open
Abstract
Functional gastrointestinal disorders (FGIDs), chronic disorders characterized by either abdominal pain, altered intestinal motility, or their combination, have a worldwide prevalence of more than 40% and impose a high socioeconomic burden with a significant decline in quality of life. Recently, FGIDs have been reclassified as disorders of gut-brain interaction (DGBI), reflecting the key role of the gut-brain bidirectional communication in these disorders and their impact on psychological comorbidities. Although, during the past decades, the field of DGBIs has advanced significantly, the molecular mechanisms underlying DGBIs pathogenesis and pathophysiology, and the role of the gut microbiome in these processes are not fully understood. This review aims to discuss the latest body of literature on the complex microbiota-gut-brain interactions and their implications in the pathogenesis of DGBIs. A better understanding of the existing communication pathways between the gut microbiome and the brain holds promise in developing effective therapeutic interventions for DGBIs.
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Affiliation(s)
- Narjis Kraimi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Taylor Ross
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Julien Pujo
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
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Zhang D, Tang Y, Bai X, Li D, Zhou M, Yu C, Wu H. Efficacy and safety of fecal microbiota transplantation for the treatment of irritable bowel syndrome: an overview of overlapping systematic reviews. Front Pharmacol 2023; 14:1264779. [PMID: 37915416 PMCID: PMC10616237 DOI: 10.3389/fphar.2023.1264779] [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: 07/25/2023] [Accepted: 10/04/2023] [Indexed: 11/03/2023] Open
Abstract
Aim: Evidence from overlapping systematic reviews (SRs) and meta-analyses (MAs) has yielded conflicting results on the treatment of irritable bowel syndrome (IBS) with fecal microbiota transplantation (FMT). To thoroughly gather, assess, and synthesize evidence on FMT for IBS, we carried out the present study. Methods: A comprehensive search was conducted in Cochrane Library, Web of Science, PubMed, and Embase from inception to May 2023. Tools for assessing the methodological quality, reporting quality, and confidence in outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Seven eligible SRs/MAs were finally included in this overview. By AMSTAR-2, the methodological quality of SRs/MAs included five that were very low quality, one that was low quality, and one that was high quality. According to PRISMA, limitations were associated with items 5 (Method: Protocol and Registration), 8 (Method: Search), and 27 (Funding). In GRADE, a total of 19 outcomes were included in the seven reviews, of which 12 outcomes were low quality and seven outcomes were moderate quality. Imprecision due to small sample size was the primary factor leading to evidence downgrading. Conclusion: We conclude that there is insufficient evidence to determine whether FMT has a more beneficial effect on patient with IBS than placebo treatment. Well-designed, larger trails are needed to provide evidence in this field. In addition, selection of donor, route of administration, dosage, and frequency still need to be determined.
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Affiliation(s)
- Di Zhang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yan Tang
- Xuyi County People’s Hospital, Huaian, China
| | - Xiangyu Bai
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Da Li
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Mengxue Zhou
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chunmei Yu
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hua Wu
- Department of Nutrition, Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China
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Jalanka J, Gunn D, Singh G, Krishnasamy S, Lingaya M, Crispie F, Finnegan L, Cotter P, James L, Nowak A, Major G, Spiller RC. Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery. Gut 2023; 72:451-459. [PMID: 36171082 PMCID: PMC9933158 DOI: 10.1136/gutjnl-2021-326828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/14/2022] [Indexed: 12/08/2022]
Abstract
OBJECTIVES Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. DESIGN A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. RESULTS PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. CONCLUSION The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD. TRIAL REGISTRATION NUMBER NCT02040922.
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Affiliation(s)
- Jonna Jalanka
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Human Microbiome Research Program, University of Helsinki Faculty of Medicine, Helsinki, Finland
| | - David Gunn
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Gulzar Singh
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Shanthi Krishnasamy
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Department of Dietetics, Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia
| | - Melanie Lingaya
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Laura Finnegan
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Paul Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Louise James
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Adam Nowak
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Giles Major
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Robin C Spiller
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
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11
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Rodrigues T, Rodrigues Fialho S, Araújo JR, Rocha R, Moreira-Rosário A. Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12051725. [PMID: 36902512 PMCID: PMC10003588 DOI: 10.3390/jcm12051725] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/07/2023] [Accepted: 02/13/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis. METHODS A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms. RESULTS Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I2 = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively). CONCLUSION Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.
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Affiliation(s)
- Tânia Rodrigues
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - Sofia Rodrigues Fialho
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - João Ricardo Araújo
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - Rita Rocha
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
| | - André Moreira-Rosário
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- Correspondence: ; Tel.: +351-218-803-000
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12
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Tuck CJ, Abu Omar A, De Palma G, Osman S, Jiménez-Vargas NN, Yu Y, Bennet SM, Lopez-Lopez C, Jaramillo-Polanco JO, Baker CC, Bennett AS, Guzman-Rodriguez M, Tsang Q, Alward T, Rolland S, Morissette C, Verdu EF, Bercik P, Vanner SJ, Lomax AE, Reed DE. Changes in signalling from faecal neuroactive metabolites following dietary modulation of IBS pain. Gut 2022; 72:gutjnl-2022-327260. [PMID: 36591617 DOI: 10.1136/gutjnl-2022-327260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 11/23/2022] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Dietary therapies for irritable bowel syndrome (IBS) have received increasing interest but predicting which patients will benefit remains a challenge due to a lack of mechanistic insight. We recently found evidence of a role for the microbiota in dietary modulation of pain signalling in a humanised mouse model of IBS. This randomised cross-over study aimed to test the hypothesis that pain relief following reduced consumption of fermentable carbohydrates is the result of changes in luminal neuroactive metabolites. DESIGN IBS (Rome IV) participants underwent four trial periods: two non-intervention periods, followed by a diet low (LFD) and high in fermentable carbohydrates for 3 weeks each. At the end of each period, participants completed questionnaires and provided stool. The effects of faecal supernatants (FS) collected before (IBS FS) and after a LFD (LFD FS) on nociceptive afferent neurons were assessed in mice using patch-clamp and ex vivo colonic afferent nerve recording techniques. RESULTS Total IBS symptom severity score and abdominal pain were reduced by the LFD (N=25; p<0.01). Excitability of neurons was increased in response to IBS FS, but this effect was reduced (p<0.01) with LFD FS from pain-responders. IBS FS from pain-responders increased mechanosensitivity of nociceptive afferent nerve axons (p<0.001), an effect lost following LFD FS administration (p=NS) or when IBS FS was administered in the presence of antagonists of histamine receptors or protease inhibitors. CONCLUSIONS In a subset of IBS patients with improvement in abdominal pain following a LFD, there is a decrease in pronociceptive signalling from FS, suggesting that changes in luminal mediators may contribute to symptom response.
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Affiliation(s)
- Caroline J Tuck
- Department of Sport, Exercise and Nutrition Sciences, La Trobe University, Melbourne, Victoria, Australia
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Amal Abu Omar
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
- Department of Physiology, Jordan University of Science and Technology, Irbid, Jordan
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Samira Osman
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Yang Yu
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Sean Mp Bennet
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Cintya Lopez-Lopez
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Corey C Baker
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Aidan Sw Bennett
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Quentin Tsang
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Taylor Alward
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Sebastien Rolland
- Department of Medicine, Hopital Maisonneuve-Rosemont, Montreal, Québec, Canada
| | - Celine Morissette
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Stephen J Vanner
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Alan E Lomax
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - David E Reed
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
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13
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Saha S, Sehgal K, Singh S, Grover M, Pardi D, Khanna S. Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis. J Clin Gastroenterol 2022; 56:e84-e93. [PMID: 34049374 PMCID: PMC8627535 DOI: 10.1097/mcg.0000000000001536] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 02/19/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis. AIM The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI). METHODS We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%. RESULTS From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias. CONCLUSIONS Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.
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Affiliation(s)
- Srishti Saha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Kanika Sehgal
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Sumitabh Singh
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Darrell Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
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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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Abstract
Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.
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Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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16
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Eijsbouts C, Zheng T, Kennedy NA, Bonfiglio F, Anderson CA, Moutsianas L, Holliday J, Shi J, Shringarpure S, Voda AI, Farrugia G, Franke A, Hübenthal M, Abecasis G, Zawistowski M, Skogholt AH, Ness-Jensen E, Hveem K, Esko T, Teder-Laving M, Zhernakova A, Camilleri M, Boeckxstaens G, Whorwell PJ, Spiller R, McVean G, D'Amato M, Jostins L, Parkes M. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat Genet 2021; 53:1543-1552. [PMID: 34741163 PMCID: PMC8571093 DOI: 10.1038/s41588-021-00950-8] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 09/08/2021] [Indexed: 12/19/2022]
Abstract
Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain-gut interactions underlying IBS.
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Affiliation(s)
- Chris Eijsbouts
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
| | - Tenghao Zheng
- Center for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- School of Biological Sciences, Monash University, Clayton, Victoria, Australia
| | - Nicholas A Kennedy
- IBD Pharmacogenetics, College of Medicine and Health, University of Exeter, Exeter, UK
| | - Ferdinando Bonfiglio
- Center for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- School of Biological Sciences, Monash University, Clayton, Victoria, Australia
| | - Carl A Anderson
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
| | - Loukas Moutsianas
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Joanne Holliday
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | | | | | - Alexandru-Ioan Voda
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
- Saint Edmund Hall, University of Oxford, Oxford, UK
| | - Gianrico Farrugia
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Matthias Hübenthal
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Department of Dermatology, Quincke Research Center, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Gonçalo Abecasis
- Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA
| | - Matthew Zawistowski
- Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA
| | - Anne Heidi Skogholt
- Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
| | - Eivind Ness-Jensen
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Kristian Hveem
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
| | - Tõnu Esko
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Maris Teder-Laving
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Alexandra Zhernakova
- Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Guy Boeckxstaens
- David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Peter J Whorwell
- Neurogastroenterology Unit, Wythenshawe Hospital, Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK
| | - Robin Spiller
- Nottingham Digestive Diseases Centre, National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Gil McVean
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Mauro D'Amato
- Center for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
- School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
- Biodonostia Health Research Institute, San Sebastian, Spain.
- Gastrointestinal Genetics Lab, CIC bioGUNE - Basque Research and Technology Alliance, Derio, Spain.
- IKERBASQUE, The Basque Science Foundation, Bilbao, Spain.
| | - Luke Jostins
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
- Christ Church, University of Oxford, Oxford, UK.
| | - Miles Parkes
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK.
- Department of Gastroenterology, Cambridge University Hospital, Cambridge, UK.
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17
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Understanding the physiology of human defaecation and disorders of continence and evacuation. Nat Rev Gastroenterol Hepatol 2021; 18:751-769. [PMID: 34373626 DOI: 10.1038/s41575-021-00487-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.
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18
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Abstract
Epidemiologic data support that acute gastrointestinal infection is one of the strongest risk factors for development of irritable bowel syndrome (IBS). Risk of post-infection IBS (PI-IBS) seems to be greater with bacterial and protozoal than viral enterocolitis. Younger individuals, women, and those with severe enterocolitis are more likely to develop PI-IBS. Disease mechanisms in animal models and humans involve chronic perturbation of intestinal microbiome, epithelial and neuronal remodeling, and immune activation. These mechanisms can lead to luminal (increased proteolytic activity, altered bile acid composition) and physiologic (increased permeability, transit changes, and visceral hypersensitivity) alterations that can mediate PI-IBS symptoms.
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Affiliation(s)
- Antonio Berumen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Adam L Edwinson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Medicine and Physiology, Enteric NeuroScience Program, 200 First Street Southwest, Rochester, MN 55905, USA.
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19
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Jalanka J, Lam C, Bennett A, Hartikainen A, Crispie F, Finnegan LA, Cotter PD, Spiller R. Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine. J Neurogastroenterol Motil 2021; 27:279-291. [PMID: 33795545 PMCID: PMC8026366 DOI: 10.5056/jnm20205] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/23/2020] [Accepted: 11/09/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient’s stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4’s downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.
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Affiliation(s)
- Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
| | - Ching Lam
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
| | - Andrew Bennett
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK.,FRAME Alternatives Laboratory, School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham, Notts, UK
| | - Anna Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Fiona Crispie
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Laura A Finnegan
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Paul D Cotter
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Robin Spiller
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
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20
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Farias e Silva K, Nanini HF, Cascabulho CM, Rosas SLB, Santana PT, Carneiro AJDV, Anaissie E, Nucci M, de Souza HSP. Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease. World J Gastroenterol 2021; 27:866-885. [PMID: 33727775 PMCID: PMC7941859 DOI: 10.3748/wjg.v27.i9.866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/11/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND 1,3-beta-D-glucan (BG) is a ubiquitous cell wall component of gut micro-organisms. We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.
AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.
METHODS A prospective observational study was performed in a tertiary referral center, from 2016 to 2019, in which serum BG was determined in 115 patients with Crohn’s disease (CD), 51 with ulcerative colitis (UC), and 82 controls using a photometric detection kit. Inflammatory activity was determined by ileocolonoscopy, histopathology, magnetic resonance enterography, and biomarkers, including fecal calprotectin (FC), C-reactive protein, and a panel of cytokines. The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve. In subgroup analysis, serial BG was used to assess the response to therapeutic interventions.
RESULTS The serum BG levels were higher in CD patients than in controls (P = 0.0001). The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients. The area under the curve (AUC) in receiver operating characteristic analysis to predict endoscopic activity was 0.694 [95% confidence interval (CI): 0.60-0.79; P = 0.001] in CD, and 0.662 (95%CI: 0.51-0.81; P = 0.066) in UC patients. The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860 (95%CI: 0.77-0.95; P < 0.001) in CD, and 0.786 (95%CI: 0.57-0.99; P = 0.015) in UC patients. The cut-off values of BG for both endoscopic and histologic activity were 60 µg/mL in CD, and 40 µg/mL in UC patients. Performance analysis showed that the results based on BG of 40 and 60 µg/mL were more specific for predicting endoscopic activity (71.8% and 87.2% for CD; and 87.5% and 87.5% for UC, respectively) than FC (53.3% and 66.7% for CD; and 20% and 80% for UC, respectively); and also histologic activity (60.5% and 76.3% for CD; and 90.0% and 95.0% for UC, respectively) than FC (41.7% and 50.0% for CD; and 25% and 50% for UC, respectively). Regarding the clinical, endoscopic, and histologic activities, the BG levels were reduced following therapeutic intervention in patients with CD (P < 0.0001) and UC (P = 0.003). Compared with endoscopic (AUC: 0.693; P = 0.002) and histologic (AUC: 0.868; P < 0.001) activity, no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography (AUC: 0.576; P = 0.192). Positive correlations were detected between BG and IL-17 in the CD (r: 0.737; P = 0.001) and the UC group (r: 0.574; P = 0.005), and between BG and interferon-gamma in the CD group (r: 0.597; P = 0.015).
CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases, particularly in CD.
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Affiliation(s)
- Katia Farias e Silva
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Hayandra F Nanini
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Cynthia Machado Cascabulho
- Laboratory of Innovations in Therapies, Education and Bioproducts, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil
| | - Siane L B Rosas
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Patricia T Santana
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Antonio José de V Carneiro
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Elias Anaissie
- Clinical Trial and Consulting Services, Cincinnati, OH 45267, United States
| | - Marcio Nucci
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Heitor Siffert Pereira de Souza
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
- Internal Medicine, D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil
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21
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Holvoet T, Joossens M, Vázquez-Castellanos JF, Christiaens E, Heyerick L, Boelens J, Verhasselt B, van Vlierberghe H, De Vos M, Raes J, De Looze D. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial. Gastroenterology 2021; 160:145-157.e8. [PMID: 32681922 DOI: 10.1053/j.gastro.2020.07.013] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 07/02/2020] [Accepted: 07/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.
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Affiliation(s)
- Tom Holvoet
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium; Faculty of Health Sciences, Ghent University, Ghent, Belgium.
| | - Marie Joossens
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | - Jorge F Vázquez-Castellanos
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | | | - Lander Heyerick
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Jerina Boelens
- Department of Medical Microbiology, Ghent University Hospital, Ghent, Belgium
| | - Bruno Verhasselt
- Department of Medical Microbiology, Ghent University Hospital, Ghent, Belgium
| | | | - Martine De Vos
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Jeroen Raes
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | - Danny De Looze
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium; Faculty of Health Sciences, Ghent University, Ghent, Belgium
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22
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Kolmeder CA, de Vos WM. Roadmap to functional characterization of the human intestinal microbiota in its interaction with the host. J Pharm Biomed Anal 2020; 194:113751. [PMID: 33328144 DOI: 10.1016/j.jpba.2020.113751] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 12/22/2022]
Abstract
It is known for more than 100 years that the intestinal microbes are important for the host's health and the last decade this is being intensely studied with a focus on the mechanistic aspects. Among the fundamental functions of the intestinal microbiome are the priming of the immune system, the production of essential vitamins and the energy harvest from foods. By now, several dozens of diseases, both intestinal and non-intestinal related, have been associated with the intestinal microbiome. Initially, this was based on the description of the composition between groups of different health status or treatment arms based on phylogenetic approaches based on the 16S rRNA gene sequences. This way of analysis has mostly moved to the analysis of all the genes or transcripts of the microbiome i.e. metagenomics and meta-transcriptomics. Differences are regularly found but these have to be taken with caution as we still do not know what the majority of genes of the intestinal microbiome are capable of doing. To circumvent this caveat researchers are studying the proteins and the metabolites of the microbiome and the host via metaproteomics and metabolomics approaches. However, also here the complexity is high and only a fraction of signals obtained with high throughput instruments can be identified and assigned to a known protein or molecule. Therefore, modern microbiome research needs advancement of existing and development of new analytical techniques. The usage of model systems like intestinal organoids where samples can be taken and processed rapidly as well as microfluidics systems may help. This review aims to elucidate what we know about the functionality of the human intestinal microbiome, what technologies are advancing this knowledge, and what innovations are still required to further evolve this actively developing field.
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Affiliation(s)
| | - Willem M de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Finland; Laboratory of Microbiology, Wageningen University, the Netherlands
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23
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Nasef NA, Mehta S. Role of Inflammation in Pathophysiology of Colonic Disease: An Update. Int J Mol Sci 2020; 21:E4748. [PMID: 32635383 PMCID: PMC7370289 DOI: 10.3390/ijms21134748] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/28/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023] Open
Abstract
Diseases of the colon are a big health burden in both men and women worldwide ranging from acute infection to cancer. Environmental and genetic factors influence disease onset and outcome in multiple colonic pathologies. The importance of inflammation in the onset, progression and outcome of multiple colonic pathologies is gaining more traction as the evidence from recent research is considered. In this review, we provide an update on the literature to understand how genetics, diet, and the gut microbiota influence the crosstalk between immune and non‑immune cells resulting in inflammation observed in multiple colonic pathologies. Specifically, we focus on four colonic diseases two of which have a more established association with inflammation (inflammatory bowel disease and colorectal cancer) while the other two have a less understood relationship with inflammation (diverticular disease and irritable bowel syndrome).
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Affiliation(s)
- Noha Ahmed Nasef
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
| | - Sunali Mehta
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
- Maurice Wilkins Centre for Biodiscovery, University of Otago, Dunedin 9054, New Zealand
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24
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Lahtinen P, Jalanka J, Hartikainen A, Mattila E, Hillilä M, Punkkinen J, Koskenpato J, Anttila VJ, Tillonen J, Satokari R, Arkkila P. Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome. Aliment Pharmacol Ther 2020; 51:1321-1331. [PMID: 32343000 DOI: 10.1111/apt.15740] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 12/14/2019] [Accepted: 03/29/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis. AIM To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS. METHODS Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight. RESULTS The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms. CONCLUSIONS FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.
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Affiliation(s)
- Perttu Lahtinen
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti, Finland.,Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Anna Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Eero Mattila
- Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
| | - Markku Hillilä
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Gastroenterology, Helsinki University Hospital, Espoo, Finland
| | - Jari Punkkinen
- Department of Gastroenterology, Porvoo Hospital, Porvoo, Finland
| | - Jari Koskenpato
- Department of Gastroenterology, Aava Medical Centre, Helsinki, Finland
| | - Veli-Jukka Anttila
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
| | - Jyrki Tillonen
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Perttu Arkkila
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
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25
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Sun JR, Kong CF, Qu XK, Deng C, Lou YN, Jia LQ. Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis. Saudi J Gastroenterol 2020; 26:66-77. [PMID: 31898645 PMCID: PMC7279071 DOI: 10.4103/sjg.sjg_384_19] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/07/2019] [Accepted: 10/26/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIM Irritable Bowel Syndrome (IBS) is a common chronic functional bowel disorder and the evidence shows most drug therapies in the treatment of IBS are weak. Recently, some studies showed probiotics may have a positive effect in IBS and they are widely used to improve the symptom of IBS, which indicate probiotics may play an important role in the treatment of IBS. However, the exact effectiveness and safety of probiotics are largely unknown. This systematic review focuses on identifying the efficacy and safety of probiotics in the treatment of IBS. MATERIALS AND METHODS Data sources were searched up to February 2019. Databases included MEDLINE, CENTRAL, CINAHL, and Embase. Randomized controlled trials (RCTs) comparing probiotics including complex or individual probiotics with placebo or no therapy were screened, extracted, and appraised by two independent reviewers. The data were pooled using a random-effects model. The methodological quality of all RCTs was assessed using the Cochrane risk of bias and Jadad scale. Outcomes included symptom-relevant and patient-relevant characteristics, such as symptom relief, abdominal pain, bloating, flatulence, quality of life, and adverse event. RESULTS This review includes 28 studies with a total of 3606 participants. Particular combinations of probiotics, or specific species and strains, showed probiotics have beneficial effect on overall IBS symptoms (22 studies, n = 3144, RR of improvement in overall IBS symptoms = 1.5, CI 1.23 to 1.83) or overall IBS symptom and abdominal pain scores (18 studies, n = 2766, SMD = -0.31, CI -0.45 to -0.17). In addition, adverse events were not significantly higher with probiotics (8 studies, n = 923, RR = 1.05; 95% CI 0.85-1.31). However, there was no significant benefit on individual IBS symptom scores and quality of life. CONCLUSION Current evidence shows particular combinations, species or strains of probiotics are effective for overall IBS symptoms. However, it is hard to derive a definite conclusion due to high heterogeneity and unclear risk of bias of some trials. Large well-designed and rigorous trials are warranted.
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Affiliation(s)
- Jian-Rong Sun
- Department of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Chen-Fan Kong
- Department of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
- Gastroenterology Department, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Xiang-Ke Qu
- Department of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
- Rheumatism Department of Traditional Chinese Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Chao Deng
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Yan-Ni Lou
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Li-Qun Jia
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
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26
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Chey WD, Shah ED, DuPont HL. Mechanism of action and therapeutic benefit of rifaximin in patients with irritable bowel syndrome: a narrative review. Therap Adv Gastroenterol 2020; 13:1756284819897531. [PMID: 32047534 PMCID: PMC6984424 DOI: 10.1177/1756284819897531] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 12/02/2019] [Indexed: 02/04/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected. Small intestinal bacterial overgrowth (SIBO) is more common in patients with IBS than in healthy individuals, and eradication of SIBO with systemic antibiotics has decreased symptoms of IBS in some patients with IBS and SIBO. The nonsystemic (i.e. low oral bioavailability) antibiotic rifaximin is indicated in the United States and Canada for the treatment of adults with IBS with diarrhea (IBS-D). The efficacy and safety of 2-week single and repeat courses of rifaximin have been demonstrated in randomized, placebo-controlled studies of adults with IBS. Rifaximin is widely thought to exert its beneficial clinical effects in IBS-D through manipulation of the gut microbiota. However, current studies indicate that rifaximin induces only modest effects on the gut microbiota of patients with IBS-D, suggesting that the efficacy of rifaximin may involve other mechanisms. Indeed, preclinical data reveal a potential role for rifaximin in the modulation of inflammatory cytokines and intestinal permeability, but these two findings have not yet been examined in the context of clinical studies. The mechanism of action of rifaximin in IBS is likely multifactorial, and further study is needed.
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Affiliation(s)
- William D. Chey
- Department of Nutrition Sciences, Division of Gastroenterology, Michigan Medicine, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109-5362, USA
| | - Eric D. Shah
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Herbert L. DuPont
- Division of Epidemiology, Human Genetics and Environmental Sciences and Center for Infectious Diseases, University of Texas School of Public Health, Houston, TX, USA
- Mary W. Kelsey Chair in Medical Sciences, Division of Internal Medicine, University of Texas McGovern Medical School Houston, TX, USA
- Kelsey Research Foundation, Houston, TX, USA
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27
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Pilla R, Suchodolski JS. The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. Front Vet Sci 2020; 6:498. [PMID: 31993446 PMCID: PMC6971114 DOI: 10.3389/fvets.2019.00498] [Citation(s) in RCA: 223] [Impact Index Per Article: 44.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/17/2019] [Indexed: 12/22/2022] Open
Abstract
The gut microbiome contributes to host metabolism, protects against pathogens, educates the immune system, and, through these basic functions, affects directly or indirectly most physiologic functions of its host. Molecular techniques have allowed us to expand our knowledge by unveiling a wide range of unculturable bacteria that were previously unknown. Most bacterial sequences identified in the canine gastrointestinal (GI) tract fall into five phyla: Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria. While there are variations in the microbiome composition along the GI tract, most clinical studies concentrate on fecal microbiota. Age, diet, and many other environmental factors may play a significant role in the maintenance of a healthy microbiome, however, the alterations they cause pale in comparison with the alterations found in diseased animals. GI dysfunctions are the most obvious association with gut dysbiosis. In dogs, intestinal inflammation, whether chronic or acute, is associated with significant differences in the composition of the intestinal microbiota. Gut dysbiosis happens when such alterations result in functional changes in the microbial transcriptome, proteome, or metabolome. Commonly affected metabolites include short-chain fatty acids, and amino acids, including tryptophan and its catabolites. A recently developed PCR-based algorithm termed “Dysbiosis Index” is a tool that allows veterinarians to quantify gut dysbiosis and can be used to monitor disease progression and response to treatment. Alterations or imbalances in the microbiota affect immune function, and strategies to manipulate the gut microbiome may be useful for GI related diseases. Antibiotic usage induces a rapid and significant drop in taxonomic richness, diversity, and evenness. For that reason, a renewed interest has been put on probiotics, prebiotics, and fecal microbiota transplantation (FMT). Although probiotics are typically unable to colonize the gut, the metabolites they produce during their transit through the GI tract can ameliorate clinical signs and modify microbiome composition. Another interesting development is FMT, which may be a promising tool to aid recovery from dysbiosis, but further studies are needed to evaluate its potential and limitations.
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Affiliation(s)
- Rachel Pilla
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, United States
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, United States
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Andrews CN, Sidani S, Marshall JK. Clinical Management of the Microbiome in Irritable Bowel Syndrome. J Can Assoc Gastroenterol 2020; 4:36-43. [PMID: 33644675 PMCID: PMC7898379 DOI: 10.1093/jcag/gwz037] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 11/15/2019] [Indexed: 12/11/2022] Open
Abstract
Background A growing body of evidence suggests that dysbiosis contributes to the onset and symptomatology of irritable bowel syndrome (IBS) and other functional bowel disorders. Changes to the gastrointestinal microbiome may contribute to the underlying pathophysiology of IBS. Methods The present review summarizes the potential effects of microbiome changes on GI transit, intestinal barrier function, immune dysregulation and inflammation, gut–brain interactions and neuropsychiatric function. Results A multimodal approach to IBS management is recommended in accordance with current Canadian guidelines. Pharmacologic treatments are advised to target the presumed underlying pathophysiological mechanism, such as dysregulation of GI transit, peristalsis, intestinal barrier function and pain signalling. The management plan for IBS may also include treatments directed at dysbiosis, including dietary modification and use of probiotics, which may promote the growth of beneficial bacteria, affect intestinal gas production and modulate the immune response; and the administration of periodic short courses of a nonsystemic antibiotic such as rifaximin, which may re-establish microbiota diversity and improve IBS symptoms. Conclusion Dysregulated host–microbiome interactions are complex and the use of microbiome-directed therapies will necessarily be empiric in individual patients. A management algorithm comprising microbiome- and nonmicrobiome-directed therapies is proposed.
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Affiliation(s)
- Christopher N Andrews
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Sacha Sidani
- Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada
| | - John K Marshall
- Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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Ghoshal UC, Rahman MM. Post-infection irritable bowel syndrome in the tropical and subtropical regions: Vibrio cholerae is a new cause of this well-known condition. Indian J Gastroenterol 2019; 38:87-94. [PMID: 31073702 DOI: 10.1007/s12664-019-00959-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| | - M Masudur Rahman
- Department of Gastroenterology, Sheikh Russel Gastroliver Institute and Hospital, Dhaka, Bangladesh
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Sadeghi A, Biglari M, Nasseri Moghaddam S. Post-infectious Irritable Bowel Syndrome: A Narrative Review. Middle East J Dig Dis 2019; 11:69-75. [PMID: 31380002 PMCID: PMC6663289 DOI: 10.15171/mejdd.2019.130] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
The Irritable bowel syndrome (IBS) is a functional disorder of alimentary system, which may be caused by infectious gastroenteritis determined as post infectious irritable bowel syndrome (PI-IBS). The prevalence of PI-IBS is reported to be 4-36% in patients with infectious gastroenteritis. The exact mechanism leading to PI-IBS is not fully understood and some factors pertaining to infectious agent and host response may have a role. Rome IV diagnostic criteria provided new definition for PI-IBS. Though it is now considered a well-defined functional disorder of gastrointestinal system, no specific treatment is yet available for PI-IBS. This article reviews the latest issues on these heading about PI-IBS.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Biglari
- Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Siavosh Nasseri Moghaddam
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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31
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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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Shin A, Preidis GA, Shulman R, Kashyap PC. The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders. Clin Gastroenterol Hepatol 2019; 17:256-274. [PMID: 30153517 PMCID: PMC6314902 DOI: 10.1016/j.cgh.2018.08.054] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 07/23/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023]
Abstract
The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggregate, independent of our ability to culture individual microbes. Early studies focused on association of changes in gut microbiota with different disease states, which was necessary to identify a potential role for microbes and generate novel hypotheses. Over the past few years the field has moved beyond associations to better understand the mechanistic implications of the microbiome in the pathophysiology of complex diseases. This movement also has resulted in a shift in our focus toward therapeutic strategies, which rely on better understanding the mediators of gut microbiota-host cross-talk. It is not surprising the gut microbiome has been implicated in the pathogenesis of functional gastrointestinal disorders given its role in modulating physiological processes such as immune development, GI motility and secretion, epithelial barrier integrity, and brain-gut communication. In this review, we focus on the current state of knowledge and future directions in microbiome research as it pertains to functional gastrointestinal disorders. We summarize the factors that help shape the gut microbiome in human beings. We discuss data from animal models and human studies to highlight existing paradigms regarding the mechanisms underlying microbiota-mediated alterations in physiological processes and their relevance in human interventions. While translation of microbiome science is still in its infancy, the outlook is optimistic and we are advancing in the right direction toward precise mechanism-based microbiota therapies.
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Affiliation(s)
- Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Geoffrey A Preidis
- Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Robert Shulman
- Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Purna C Kashyap
- Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Barbara G, Grover M, Bercik P, Corsetti M, Ghoshal UC, Ohman L, Rajilić-Stojanović M. Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome. Gastroenterology 2019; 156:46-58.e7. [PMID: 30009817 PMCID: PMC6309514 DOI: 10.1053/j.gastro.2018.07.011] [Citation(s) in RCA: 143] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 07/03/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience. METHODS The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. RESULTS PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. CONCLUSIONS Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.
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Affiliation(s)
- Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Madhusudan Grover
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Premysl Bercik
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Centre, National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham, UK
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Lena Ohman
- Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Mirjana Rajilić-Stojanović
- Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
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Rahman MM, Ghoshal UC, Sultana S, Kibria MG, Sultana N, Khan ZA, Ahmed F, Hasan M, Ahmed T, Sarker SA. Long-Term Gastrointestinal Consequences are Frequent Following Sporadic Acute Infectious Diarrhea in a Tropical Country: A Prospective Cohort Study. Am J Gastroenterol 2018; 113:1363-1375. [PMID: 30171215 DOI: 10.1038/s41395-018-0208-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 06/07/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Postinfection irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD), though reported from the temperate countries, have not been studied in the tropics; PI-malabsorption syndrome (MAS), which mimics PI-IBS, is reported from the tropics. No report till date on PI-IBS excluded PI-MAS. We studied: (i) the frequency of continuing bowel dysfunction after acute gastroenteritis (AG), (ii) its predictors, and (iii) PI-MAS among patients with PI-IBS. METHODS 345 consecutive subjects each, with AG and age- and gender-matched healthy controls were followed up 3-monthly for 12 months using a translated-validated questionnaire and functional gastrointestinal disorders (FGIDs) were diagnosed by Rome III criteria. Symptom duration >3 months but <6 months was diagnosed as chronic bowel dysfunction (CBD) and dyspeptic symptoms, respectively. MAS was diagnosed if 2/3 tests (D-xylose H2 breath test, Sudan III-stained stool microscopy, and duodenal histology) were abnormal. Fecal microbiological studies were performed in 245/345 (71%) patients. RESULTS AG patients more often developed PI-IBS and PI-FD than controls (16.5 vs. 2.6% and 7.4 vs. 0.6%, respectively; p<0.001). Presence of FD was a risk factor for PI-IBS and IBS for PI-FD. On multivariate analysis, dyspeptic symptoms, CBD, and weight loss were the risk factors for PI-FGIDs. The frequency of PI-IBS following Vibrio cholera and other bacterial infection was comparable. Malabsorption was present among 2/23 (9%) patients with PI-IBS. CONCLUSION FGIDs are common after AG; dyspeptic symptoms, CBD, and weight loss were risk factors for PI-FGIDs. Vibrio cholerae infection caused PI-FGID, which was never reported. About 9 % patients fulfilling the criteria for PI-IBS had PI-MAS.
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Affiliation(s)
- Masudur M Rahman
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Shamima Sultana
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Md Golam Kibria
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Nigar Sultana
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Zeenat Arefin Khan
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Faruque Ahmed
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Mahmud Hasan
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Tahmeed Ahmed
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
| | - Shafiqul Alam Sarker
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh. Department of Gastroenterology, Sanjay Gandhi Postgraduate institute of Medical sciences, Lucknow, india. Nutrition and clinical service division, international center for diarrheal disease Research, dhaka, Bangladesh. Gastroliver Foundation, dhaka, Bangladesh. These authors contributed equally: M. Masudur rahman, uday c. ghoshal
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Moser G, Fournier C, Peter J. Intestinal microbiome-gut-brain axis and irritable bowel syndrome. Wien Med Wochenschr 2018; 168:62-66. [PMID: 28887729 PMCID: PMC5860136 DOI: 10.1007/s10354-017-0592-0] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 07/26/2017] [Indexed: 02/06/2023]
Abstract
Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.
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Affiliation(s)
- Gabriele Moser
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
| | - Camille Fournier
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria
| | - Johannes Peter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria
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Cameron D, Hock QS, Kadim M, Mohan N, Ryoo E, Sandhu B, Yamashiro Y, Jie C, Hoekstra H, Guarino A. Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region. World J Gastroenterol 2017; 23:7952-7964. [PMID: 29259371 PMCID: PMC5725290 DOI: 10.3748/wjg.v23.i45.7952] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 09/29/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023] Open
Abstract
Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.
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Affiliation(s)
- Donald Cameron
- Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital, Melbourne 3052, Australia
| | - Quak Seng Hock
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Musal Kadim
- Child Health Department, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta 12220, Indonesia
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology And Liver Transplantation, Medanta The Medicity 122001, Gurugram Haryana, India
| | - Eell Ryoo
- Department of Pediatrics, Gachon University, Gil Gachon Children’s Hosptial, Incheon 21565, South Korea
| | - Bhupinder Sandhu
- Department of Paediatric Gastroenterology, Royal Hospital for Children, Bristol BS2 8BJ, United Kingdom
| | - Yuichiro Yamashiro
- Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - Chen Jie
- The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 610041, Zhejiang Province, China
| | - Hans Hoekstra
- Department of Pediatrics, Hieronymus Bosch Hospital, ’s-Hertogenbosch 5223GZ, The Netherlands
| | - Alfredo Guarino
- Unit of Pediatrics Infectious Diseases and Clinical Nutrition of the Department of Translational Medical Science-Section of Pediatrics, University of Naples Federico II, Naples 80131, Italy
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Postinfection Irritable Bowel Syndrome: The Links Between Gastroenteritis, Inflammation, the Microbiome, and Functional Disease. J Clin Gastroenterol 2017; 51:869-877. [PMID: 28885302 DOI: 10.1097/mcg.0000000000000924] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Postinfection irritable bowel syndrome (PI-IBS) is a diarrheal disease that develops after infectious gastroenteritis (IGE). Profound alterations in the microbiota accompany IGE yet only 10% of IGE patients progress to PI-IBS. This review explores research linking IGE severity, psychological comorbidity, PI-IBS, and the microbiome in various patient populations. Selective pressures caused by inflammation and increased gastrointestinal motility during gastroenteritis can alter intestinal bacterial phyla including Bacteroidetes, Firmicutes, and Proteobacteria. More specifically, classes such as Bacteroides and Clostridia are differentially abundant in many PI-IBS patients. Altered microbiota may perpetuate a cycle of enteric and systemic inflammation, potently activating neural afferent signaling in the enteric nervous system and causing pain and diarrhea in PI-IBS patients. Altered production of microbial metabolites, for example short chain fatty acids, may have enteric and systemic effects on the host. Longitudinal sampling to characterize changes in the microbiota's genetic, metabolic, and transcriptional activities over time from IGE to PI-IBS may enable improved diagnosis and classification of PI-IBS cases into subtypes, allowing for targeted antibiotic, probiotic, and prebiotic treatments. PI-IBS is a heterogenous and largely organic disease marked by specific alterations in functions of the microbiota and is an important model for studying microbial influences on intestinal, neurological, and psychological host functions.
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Riddle CAPTMS, Martin GJ, Murray COLCK, Burgess CAPTTH, Connor CP, Mancuso COLJD, Schnaubelt MER, Ballard LCTP, Fraser J, Tribble DR. Management of Acute Diarrheal Illness During Deployment: A Deployment Health Guideline and Expert Panel Report. Mil Med 2017; 182:34-52. [PMID: 28885922 PMCID: PMC5657341 DOI: 10.7205/milmed-d-17-00077] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Acute diarrheal illness during deployment causes significant morbidity and loss of duty days. Effective and timely treatment is needed to reduce individual, unit, and health system performance impacts. METHODS This critical appraisal of the literature, as part of the development of expert consensus guidelines, asked several key questions related to self-care and healthcare-seeking behavior, antibiotics for self-treatment of travelers' diarrhea, what antibiotics/regimens should be considered for treatment of acute watery diarrhea and febrile diarrhea and/or dysentery, and when and what laboratory diagnostics should be used to support management of deployment-related travelers' diarrhea. Studies of acute diarrhea management in military and other travelers were assessed for relevance and quality. On the basis of this critical appraisal, guideline recommendations were developed and graded by the Expert Panel using good standards in clinical guideline development methodology. RESULTS New definitions for defining the severity of diarrhea during deployment were established. A total of 13 graded recommendations on the topics of prophylaxis, therapy and diagnosis, and follow-up were developed. In addition, four non-graded consensus-based statements were adopted. CONCLUSIONS Successful management of acute diarrheal illness during deployment requires action at the provider, population, and commander levels. Strong evidence supports that single-dose antimicrobial therapy is effective in most cases of moderate to severe acute diarrheal illness during deployment. Further studies are needed to address gaps in available knowledge regarding optimal therapies for treatment, prevention, and laboratory testing of acute diarrheal illness.
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Affiliation(s)
- CAPT Mark S. Riddle
- Enteric Disease Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
| | - Gregory J. Martin
- Chief, Tropical Medicine-Infectious Diseases, Bureau of Medical Services, US Department of State, 2401 E St NW L209, Washington DC 20037, USA
| | - COL Clinton K. Murray
- Deputy Medical Corps Chief, Medical Corps Specific Branch Proponent Officer, Infectious Disease Consultant to the Army Surgeon General, Brooke Army Medical Center, 3551 Roger Brooke Dr, JBSA Fort Sam Houston, TX 78234, USA
| | - CAPT Timothy H. Burgess
- Infectious Disease Clinical Research Program, Preventive Medicine & Biostatistics Department, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Col Patrick Connor
- Military Enteric Disease Group, Academic Department of Military Medicine, Birmingham Research Park, Vincent Drive, Birmingham B15 2SQ, United Kingdom
| | - COL James D. Mancuso
- Department of Preventive Medicine & Biostatistics, The F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Maj Elizabeth R. Schnaubelt
- Infectious Disease Service, Landstuhl Regional Medical Center, Landstuhl, Germany, CMR 402, APO, AE, 19180, USA [Current Affiliation: Division of Global HIV and TB, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333, USA]
| | - Lt Col Timothy P. Ballard
- Operational Medicine, Defense Institute for Medical Operations, 1320 Truemper St, Bldg 9122, JBSA-Lackland, TX 78236, USA
| | - Jamie Fraser
- Infectious Disease Clinical Research Program, Preventive Medicine & Biostatistics Department, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr #100, Bethesda, MD 20817, USA
| | - David R. Tribble
- Infectious Disease Clinical Research Program, Preventive Medicine & Biostatistics Department, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
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Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, Libman M, Steffen R, Taylor D, Tribble DR, Vila J, Zanger P, Ericsson CD. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med 2017; 24:S57-S74. [PMID: 28521004 PMCID: PMC5731448 DOI: 10.1093/jtm/tax026] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND : Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. METHODS : This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. RESULTS : New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. CONCLUSIONS : Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea.
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Affiliation(s)
| | - Bradley A. Connor
- Weill Cornell Medical College and The New York Center for Travel and
Tropical Medicine, New York, NY, USA
| | - Nicholas J. Beeching
- Clinical Science Group, Liverpool School of Tropical Medicine, Pembroke
Place, Liverpool, UK and National Institute of Health Research (NIHR) Health Protection Unit
in Gastrointestinal Infections, Farr Institute, University of Liverpool, Liverpool, UK
| | | | - Davidson H. Hamer
- Department of Global Health, Center for Global Health and Development,
Boston University School of Public Health, Section of Infectious Diseases, Department of
Medicine, Boston University School of Medicine, Boston, MA, USA
| | | | - Michael Libman
- J.D. MacLean Centre for Tropical Diseases, McGill University, Montreal,
Québec, Canada
| | - Robert Steffen
- Epidemiology, Biostatistics and Prevention Institute, World Health
Organization Collaborating Centre for Traveller's Health, University of Zurich, Zurich,
Switzerland
| | | | - David R. Tribble
- Uniformed Services University of the Health Sciences, Bethesda, MD,
USA
| | - Jordi Vila
- ISGlobal, Barcelona Centre for International Health Research, Hospital
Clínic–Universitat de Barcelona, Barcelona, Spain
| | - Philipp Zanger
- Institute of Public Health, University Hospitals,
Ruprecht-Karls-Universität, Heidelberg, Germany
| | - Charles D. Ericsson
- Department of Medicine, Division of Infectious Diseases, University of
Texas Medical School at Houston, Houston, TX, USA
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Zhuang X, Xiong L, Li L, Li M, Chen M. Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta-analysis. J Gastroenterol Hepatol 2017; 32:28-38. [PMID: 27300149 DOI: 10.1111/jgh.13471] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Alterations of gut microbiota were assumed to be the etiology and pathogenesis of irritable bowel syndrome (IBS) in some studies. However, alterations of gut microbiota in IBS patients had not been systematically assessed with a meta-analysis. We performed a mate-analysis to explore and compare the alterations of gut microbiota in IBS patients from China and other regions around the world. METHODS Case-control studies detecting gut microbiota in IBS patients were identified through English and Chinese databases. The standardized mean difference (SMD) with 95% confidence interval (CI) of bacterial counts was calculated. RESULTS Ten studies from China and seven studies from other regions around the world were included in our study. As compared with healthy controls, the SMDs of Bifidobacteria, Lactobacillus, Escherichia Coli, and Enterobacter in Chinese IBS patients were -1.42 (CI: -2.10, -0.75), -0.91 (95% CI: -1.31, -0.52), 0.83 (95% CI: 0.26, 1.40), and 0.57 (95% CI: 0.33, 0.82), respectively. But the SMDs of Bacteroides and Enterococcus were found no significant differences in Chinese IBS patients. However, the SMDs of Bifidobacteria and Bacteroides in IBS patients from other regions were -0.76 (CI: -1.43, -0.09) and 1.17 (CI: 0.00, 2.35), while the SMDs of Lactobacillus, E. Coli, Enterobacter, and Enterococcus were found no significant differences. CONCLUSIONS There were alterations of gut microbiota in IBS patients, and it implied that alterations of gut microbiota might be involved in the pathogenesis of IBS. However, the species-specific alterations of gut microbiota were different between IBS patients from China and other regions.
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Affiliation(s)
- Xiaojun Zhuang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lishou Xiong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li Li
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Manying Li
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol 2017; 312:G52-G62. [PMID: 27881403 PMCID: PMC5283907 DOI: 10.1152/ajpgi.00338.2016] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 11/07/2016] [Accepted: 11/16/2016] [Indexed: 01/31/2023]
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders. Despite its prevalence, the pathophysiology of IBS is not well understood although multiple peripheral and central factors are implicated. Recent studies suggest a role for alterations in gut microbiota in IBS. Significant advances in next-generation sequencing technology and bioinformatics and the declining cost have now allowed us to better investigate the role of gut microbiota in IBS. In the following review, we propose gut microbiota as a unifying factor in the pathophysiology of IBS. We first describe how gut microbiota can be influenced by factors predisposing individuals to IBS such as host genetics, stress, diet, antibiotics, and early life experiences. We then highlight the known effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS including disrupted gut brain axis (GBA), visceral hypersensitivity (VH), altered GI motility, epithelial barrier dysfunction, and immune activation. While there are several gaps in the field that preclude us from connecting the dots to establish causation, we hope this overview will allow us to identify and fill in the voids.
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Affiliation(s)
- Yogesh Bhattarai
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David A. Muniz Pedrogo
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Purna C. Kashyap
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Collins SM. The Intestinal Microbiota in the Irritable Bowel Syndrome. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2016; 131:247-261. [PMID: 27793222 DOI: 10.1016/bs.irn.2016.08.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The irritable bowel syndrome (IBS) is a chronic abdominal symptom complex occurring in a bowel devoid of discernible relevant pathology. There is growing interest in the role of the intestinal microbiota as a basis for the intestinal and possibly behavioral manifestations of this condition. Molecular-based microbial profiling has revealed compositional changes in the microbiota of at least a subset of IBS patients but the data are often conflicting and no microbial signature for this condition has yet been defined. Animal studies in which a previously stable intestinal microbiota is perturbed, by antibiotics or dietary change, results in alterations in intestinal function reminiscent of that seen in IBS patients. These include visceral sensitivity to painful stimuli, altered motility and intestinal barrier function as well as immune activation, and low-grade inflammation. More recent studies have shown that perturbation of the microbial composition of the gut alters brain chemistry and behavior. In a step toward establishing a causal link between an altar microbiota and gut-brain manifestations of IBS, colonization of germ-free mice with microbiota from IBS patients results in an IBS-like phenotype, including alterations and behavior if the donor exhibited psychiatric comorbidity, such as high levels of anxiety. This model provides an opportunity for exploring the mechanisms underlying host-microbe interactions relevant to the pathogenesis of IBS and for developing novel therapeutic targets.
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Affiliation(s)
- S M Collins
- The Farncombe Family Digestive Health Research Centre, The Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
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Jin DC, Cao HL, Xu MQ, Wang SN, Wang YM, Yan F, Wang BM. Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome. World J Gastroenterol 2016; 22:8137-8148. [PMID: 27688655 PMCID: PMC5037082 DOI: 10.3748/wjg.v22.i36.8137] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/28/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.
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Martin-Viñas JJ, Quigley EMM. Immune response in irritable bowel syndrome: A systematic review of systemic and mucosal inflammatory mediators. J Dig Dis 2016; 17:572-581. [PMID: 27426409 DOI: 10.1111/1751-2980.12379] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 06/21/2016] [Accepted: 07/04/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To systematically review the available data on cytokine and immune cells in the peripheral blood and mucosal biopsy samples from patients with irritable bowel syndrome (IBS). METHODS From a review of the literature, data on cytokines and immune cells that had been assayed in at least three independent studies were collated and trends examined. RESULTS Levels of interleukin (IL)-10 tended to be decreased and those of IL-6, IL-8, tumor necrosis factor-α and IL-1β increased in the systemic circulation in IBS, while in the mucosa, IL-10 was decreased and IL-8, mast cells, enterochromaffin cells and CD3+ T lymphocytes were increased. However, these findings were not consistent across all studies and, in some instances, were limited to certain IBS sub-populations. CONCLUSIONS The interpretation of this literature is limited by several factors, such as the intrinsic heterogeneity of IBS and a lack of standardization in study design. While a number of intriguing immunological observations have been made in IBS, more work is needed before a compelling case can be made for a role for immune-mediated events in the etiology of IBS.
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Affiliation(s)
- Juan J Martin-Viñas
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
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Feliciano RP, Istas G, Heiss C, Rodriguez-Mateos A. Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry. Molecules 2016; 21:molecules21091120. [PMID: 27571052 PMCID: PMC6273248 DOI: 10.3390/molecules21091120] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 08/17/2016] [Accepted: 08/17/2016] [Indexed: 01/11/2023] Open
Abstract
Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%–48% in plasma and 47%–54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption.
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Affiliation(s)
- Rodrigo P Feliciano
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany.
| | - Geoffrey Istas
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany.
| | - Christian Heiss
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany.
| | - Ana Rodriguez-Mateos
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany.
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Ponziani FR, Pecere S, Lopetuso L, Scaldaferri F, Cammarota G, Gasbarrini A. Rifaximin for the treatment of irritable bowel syndrome - a drug safety evaluation. Expert Opin Drug Saf 2016; 15:983-91. [PMID: 27149541 DOI: 10.1080/14740338.2016.1186639] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Irritable bowel syndrome is a functional gastrointestinal disorder with a multifactorial etiology. Alterations of intestinal motility and immunity, gut-brain interactions, as well as gut microbiota dysbiosis contribute to the development of irritable bowel syndrome. Therefore, gut microbiota modulation by non-absorbable antibiotics is a therapeutic option in patients with IBS. AREAS COVERED Published articles including patients with irritable bowel syndrome reporting data about rifaximin activity and safety have been searched throughout the literature and selected. EXPERT OPINION The optimal antibiotic molecule should be local-acting, long-acting and safe-acting. Rifaximin is a non-absorbable antibiotic with additional anti-inflammatory and gut microbiota-modulating activity. It is effective in inducing symptoms relief in patients with IBS, even after repeated treatment courses. Rifaximin-related side effects in patients with IBS are reported to be mild and infrequent; microbial resistance is rare and transient, due to the high local concentration of the drug and to the absence of horizontal transmission. Clostridium difficile infection is not usual in patients receiving rifaximin in absence of predisposing conditions such as hospitalization and immunosuppression, which are uncommon in patients affected by irritable bowel syndrome. Nevertheless rifaximin is an antibiotic active against Clostridium difficile infection. Rifaximin has limited metabolic interactions and is not expected to interfere with drug metabolism in patients with normal hepatic function. These properties make rifaximin a safe antibiotic for gut microbiota modulation in patients with IBS.
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Affiliation(s)
| | - Silvia Pecere
- a Internal Medicine and Gastroenterology Division , A. Gemelli Hospital Rome , Rome , Italy
| | - Loris Lopetuso
- a Internal Medicine and Gastroenterology Division , A. Gemelli Hospital Rome , Rome , Italy
| | - Franco Scaldaferri
- a Internal Medicine and Gastroenterology Division , A. Gemelli Hospital Rome , Rome , Italy
| | - Giovanni Cammarota
- a Internal Medicine and Gastroenterology Division , A. Gemelli Hospital Rome , Rome , Italy
| | - Antonio Gasbarrini
- a Internal Medicine and Gastroenterology Division , A. Gemelli Hospital Rome , Rome , Italy
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Fourie NH, Wang D, Abey SK, Sherwin LB, Joseph PV, Rahim-Williams B, Ferguson EG, Henderson WA. The microbiome of the oral mucosa in irritable bowel syndrome. Gut Microbes 2016; 7:286-301. [PMID: 26963804 PMCID: PMC4988452 DOI: 10.1080/19490976.2016.1162363] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS.
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Affiliation(s)
- Nicolaas H. Fourie
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Dan Wang
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Sarah K. Abey
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - LeeAnne B. Sherwin
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Paule V. Joseph
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Bridgett Rahim-Williams
- National Institute on Minority Health and Health Disparities, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Eric G. Ferguson
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
| | - Wendy A. Henderson
- Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, DHHS, Bethesda, MD, USA
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