|
1
|
Karimi M, Shirsalimi N, Hashempour Z, Salehi Omran H, Sedighi E, Beigi F, Mortezazadeh M. Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review. Front Immunol 2024; 15:1439176. [PMID: 39391303 PMCID: PMC11464302 DOI: 10.3389/fimmu.2024.1439176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.
Collapse
Affiliation(s)
- Mehdi Karimi
- Bogomolets National Medical University (NMU), Kyiv, Ukraine
| | - Niyousha Shirsalimi
- Faculty of Medicine, Hamadan University of Medical Science (UMSHA), Hamadan, Iran
| | - Zahra Hashempour
- School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, Iran
| | - Hossein Salehi Omran
- School of Medicine, Shahid Beheshti University of Medical Sciences (SBMUS), Tehran, Iran
| | - Eshagh Sedighi
- Department of Veterinary Medicine, Islamic Azad University Branch of Urmia, Urmia, Iran
| | - Farzan Beigi
- Students Research Committee, Arak University of Medical Sciences, Arak, Iran
| | - Masoud Mortezazadeh
- Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| |
Collapse
|
|
2
|
Maaskant A, Voermans B, Levin E, de Goffau MC, Plomp N, Schuren F, Remarque EJ, Smits A, Langermans JAM, Bakker J, Montijn R. Microbiome signature suggestive of lactose-intolerance in rhesus macaques (Macaca mulatta) with intermittent chronic diarrhea. Anim Microbiome 2024; 6:53. [PMID: 39313845 PMCID: PMC11421201 DOI: 10.1186/s42523-024-00338-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 09/06/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND Chronic diarrhea is a common cause of mortality and morbidity in captive rhesus macaques (Macaca mulatta). The exact etiology of chronic diarrhea in macaques remains unidentified. The occurrence of diarrhea is frequently linked to dysbiosis within the gut microbiome. Research into microbiome signatures correlated with diarrhea in macaques have predominantly been conducted with single sample collections. Our analysis was based on the metagenomic composition of longitudinally acquired fecal samples from rhesus macaques with chronic diarrhea and clinically healthy rhesus macaques that were obtained over the course of two years. We aimed to investigate potential relationships between the macaque gut microbiome, the presence of diarrhea and diet interventions with a selection of commercially available monkey diets. RESULTS The microbiome signature of macaques with intermittent chronic diarrhea showed a significant increase in lactate producing bacteria e.g. lactobacilli, and an increase in fermenters of lactate and succinate. Strikingly, two lactose free diets were associated with a lower incidence of diarrhea. CONCLUSION A lactose intolerance mechanism is suggested in these animals by the bloom of Lactobacillus in the presence of lactose resulting in an overproduction of intermediate fermentation products likely led to osmotically induced diarrhea. This study provides new insights into suspected microbiome-lactose intolerance relationship in rhesus macaques with intermittent chronic diarrhea. The integration of machine learning with metagenomic data analysis holds potential for developing targeted dietary interventions and therapeutic strategies and therefore ensuring a healthier and more resilient primate population.
Collapse
Affiliation(s)
- Annemiek Maaskant
- Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands.
- Department Population Health Sciences, Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Heidelberglaan 8, 3584 CM, Utrecht, The Netherlands.
| | - Bas Voermans
- HORAIZON Technology BV, Marshallaan 2, 2625 GZ, Delft, The Netherlands.
- Department of Vascular Medicine, Amsterdam UMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Evgeni Levin
- HORAIZON Technology BV, Marshallaan 2, 2625 GZ, Delft, The Netherlands
| | - Marcus C de Goffau
- HORAIZON Technology BV, Marshallaan 2, 2625 GZ, Delft, The Netherlands
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK
| | - Nicole Plomp
- Department of Microbiology and Systems Biology, Organization for Applied Scientific Research (TNO), Sylviusweg 71, 2333 BE, Leiden, The Netherlands
| | - Frank Schuren
- Department of Microbiology and Systems Biology, Organization for Applied Scientific Research (TNO), Sylviusweg 71, 2333 BE, Leiden, The Netherlands
| | - Edmond J Remarque
- Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands
| | - Antoine Smits
- Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands
| | - Jan A M Langermans
- Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands
- Department Population Health Sciences, Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Heidelberglaan 8, 3584 CM, Utrecht, The Netherlands
| | - Jaco Bakker
- Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands
| | - Roy Montijn
- Department of Microbiology and Systems Biology, Organization for Applied Scientific Research (TNO), Sylviusweg 71, 2333 BE, Leiden, The Netherlands
| |
Collapse
|
|
3
|
Severino A, Tohumcu E, Tamai L, Dargenio P, Porcari S, Rondinella D, Venturini I, Maida M, Gasbarrini A, Cammarota G, Ianiro G. The microbiome-driven impact of western diet in the development of noncommunicable chronic disorders. Best Pract Res Clin Gastroenterol 2024; 72:101923. [PMID: 39645277 DOI: 10.1016/j.bpg.2024.101923] [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: 04/14/2024] [Accepted: 05/02/2024] [Indexed: 07/23/2024]
Abstract
Noncommunicable chronic disorders (NCDs) are multifactorial disorders that share a state of chronic, low-grade inflammation together with an imbalance of gut microbiota. NCDs are becoming increasingly prevalent worldwide, and mainly in Western countries, with a significant impact on global health. Societal changes, together with the widespread diffusion of modern agricultural methods and food processing, have led to a significant shift in dietary habits over the past century, with an increased diffusion of the Western diet (WD). WD includes foods high in saturated fat, refined sugars, salt, sweeteners, and low in fiber, and is characterized by overeating, frequent snacking, and a prolonged postprandial state. An increasing body of evidence supports the association between the diffusion of WD and the rising prevalence of NCDs. WD also negatively affects both gut microbiota and the immune system by driving to microbial alterations, gut barrier dysfunction, increased intestinal permeability, and leakage of harmful bacterial metabolites into the bloodstream, with consequent contribution to the development of systemic low-grade inflammation. In this review article we aim to dissect the role of gut microbiota imbalance and gut barrier impairment in mediating the detrimental effects of WD on the development of NCDs, and to identify potential therapeutic strategies.
Collapse
Affiliation(s)
- Andrea Severino
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
| | - Ege Tohumcu
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Luca Tamai
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Pasquale Dargenio
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Serena Porcari
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Debora Rondinella
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Irene Venturini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Marcello Maida
- Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| |
Collapse
|
|
4
|
Iribarren C, Savolainen O, Sapnara M, Törnblom H, Simrén M, Magnusson MK, Öhman L. Temporal stability of fecal metabolomic profiles in irritable bowel syndrome. Neurogastroenterol Motil 2024; 36:e14741. [PMID: 38243381 DOI: 10.1111/nmo.14741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 11/15/2023] [Accepted: 01/04/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects. METHODS Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects. For Cohort A, fecal samples collected during 5 consecutive days were analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS). For Cohort B, liquid chromatography-MS (LC-MS) was used to analyze fecal samples collected at week 0 (healthy and IBS) and at week 4 (patients only). Stool consistency was determined by the Bristol Stool Form scale. KEY RESULTS Fecal samples were collected from Cohort A (seven healthy subjects and eight IBS patients), and Cohort B (seven healthy subjects and 11 IBS patients). The fecal metabolome of IBS patients was stable short-term (Cohort A, 5 days and within the same day) and long-term (Cohort B, 4 weeks). A similar trend was observed over 5 days in the healthy subjects of Cohort A. The metabolome dissimilarity was larger between than within participants over time in both healthy subjects and IBS patients. Further analyses showed that patients had greater range of stool forms (types) than healthy subjects, with no apparent influence on metabolomic dynamics. CONCLUSION & INFERENCES The fecal metabolome is stable over time within IBS patients as well as healthy subjects. This supports the concept of a stable fecal metabolome in IBS despite fluctuations in stool consistency, and the use of single timepoint sampling to further explore how the fecal metabolome is related to IBS pathogenesis.
Collapse
Affiliation(s)
- Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Otto Savolainen
- Chalmers Mass Spectrometry Infrastructure, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Maria Sapnara
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Maria K Magnusson
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
5
|
Staudacher HM, Mahoney S, Canale K, Opie RS, Loughman A, So D, Beswick L, Hair C, Jacka FN. Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2024; 59:492-503. [PMID: 37969059 DOI: 10.1111/apt.17791] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/17/2023] [Accepted: 10/20/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND Diet is fundamental to the care of irritable bowel syndrome (IBS). However, some approaches are not appropriate for individuals experiencing psychological symptoms. AIMS To assess feasibility of a Mediterranean diet in IBS and its impact on gastrointestinal and psychological symptoms. METHODS We recruited adults with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms to an unblinded 6-week randomised controlled trial. Patients were randomised to Mediterranean diet counselling or habitual diet. We collected gastrointestinal and psychological symptom data, dietary data and stool samples for metagenomic sequencing. RESULTS We randomised 59 individuals (29 Mediterranean diet, 30 control); 48 completed the study. The Mediterranean Diet Adherence Screener score was higher in the Mediterranean diet group than controls at week 6 (7.5 [95% CI: 6.9-8.0] vs. 5.7 [5.2-6.3], p < 0.001), and there was a greater score increase than controls (2.1 [95% CI: 1.3-2.9] vs. 0.5 [95% CI: 0.1-1.0], p = 0.004), demonstrating Mediterranean diet feasibility. There was a greater proportion of gastrointestinal symptom responders in the Mediterranean diet group than controls (24/29, 83% vs. 11/30, 37%, p < 0.001) and depression responders (15/29, 52% vs. 6/30 20%, p = 0.015). There was no difference in FODMAP intake at week 6 (p = 0.51). Gastrointestinal adverse events were similar (p = 0.588). There were no differences in change in microbiome parameters between groups. CONCLUSIONS A Mediterranean diet is feasible in IBS and leads to improvement in gastrointestinal and psychological symptoms. Although this study was unblinded, these findings together with the broader benefits of the Mediterranean diet, provide strong impetus for future research in IBS. Australia New Zealand Clinical Trials Registry: ACTRN12620001362987.
Collapse
Affiliation(s)
- Heidi M Staudacher
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Sophie Mahoney
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Kim Canale
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Rachelle S Opie
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Amy Loughman
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Daniel So
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
- Department of Nutritional Sciences, King's College London, London, UK
| | - Lauren Beswick
- Department of Gastroenterology, Barwon Health, Geelong, Victoria, Australia
- School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Chris Hair
- Department of Gastroenterology, Barwon Health, Geelong, Victoria, Australia
- School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Felice N Jacka
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
- Centre for Adolescent Health, Murdoch Children's Research Institute, Parkville, Victoria, Australia
| |
Collapse
|
|
6
|
An R, Wilms E, Gerritsen J, Kim HK, Pérez CS, Besseling-van der Vaart I, Jonkers DM, Rijkers GT, de Vos WM, Masclee AA, Zoetendal EG, Troost FJ, Smidt H. Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic. Gut Microbes 2024; 16:2350173. [PMID: 38738780 PMCID: PMC11093041 DOI: 10.1080/19490976.2024.2350173] [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: 01/06/2024] [Accepted: 04/26/2024] [Indexed: 05/14/2024] Open
Abstract
Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.
Collapse
Affiliation(s)
- Ran An
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Department of Food science and Technology, Shanghai Jiao Tong University, Shanghai, China
| | - Ellen Wilms
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Jacoline Gerritsen
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Winclove Probiotics, Amsterdam, The Netherlands
| | - Hye Kyong Kim
- Institute of Biology, Leiden University, Leiden, The Netherlands
| | - Celia Seguí Pérez
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Winclove Probiotics, Amsterdam, The Netherlands
- Infectious Diseases & Immunology, University of Utrecht, Utrecht, The Netherland
| | | | - Daisy M.A.E. Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Ger T. Rijkers
- Science Department, University College Roosevelt, Middelburg, The Netherlands
| | - Willem M. de Vos
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Human Microbiomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Ad A.M. Masclee
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Erwin G. Zoetendal
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Freddy J. Troost
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
- Food Innovation and Health, Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Venlo, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| |
Collapse
|
|
7
|
Tang H, Chen X, Huang S, Yin G, Wang X, Shen G. Targeting the gut-microbiota-brain axis in irritable bowel disease to improve cognitive function - recent knowledge and emerging therapeutic opportunities. Rev Neurosci 2023; 34:763-773. [PMID: 36757367 DOI: 10.1515/revneuro-2022-0155] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/21/2023] [Indexed: 02/10/2023]
Abstract
The brain-gut axis forms a bidirectional communication system between the gastrointestinal (GI) tract and cognitive brain areas. Disturbances to this system in disease states such as inflammatory bowel disease have consequences for neuronal activity and subsequent cognitive function. The gut-microbiota-brain axis refers to the communication between gut-resident bacteria and the brain. This circuits exists to detect gut microorganisms and relay information to specific areas of the central nervous system (CNS) that in turn, regulate gut physiology. Changes in both the stability and diversity of the gut microbiota have been implicated in several neuronal disorders, including depression, autism spectrum disorder Parkinson's disease, Alzheimer's disease and multiple sclerosis. Correcting this imbalance with medicinal herbs, the metabolic products of dysregulated bacteria and probiotics have shown hope for the treatment of these neuronal disorders. In this review, we focus on recent advances in our understanding of the intricate connections between the gut-microbiota and the brain. We discuss the contribution of gut microbiota to neuronal disorders and the tangible links between diseases of the GI tract with cognitive function and behaviour. In this regard, we focus on irritable bowel syndrome (IBS) given its strong links to brain function and anxiety disorders. This adds to the growing body of evidence supporting targeted therapeutic strategies to modulate the gut microbiota for the treatment of brain/mental-health-related disease.
Collapse
Affiliation(s)
- Heyong Tang
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, No. 1, Qianjiang Road, 230012 Hefei, Anhui, China
| | - Xiaoqi Chen
- School of Acupuncture and Massage, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, China
| | - Shun Huang
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, No. 1, Qianjiang Road, 230012 Hefei, Anhui, China
| | - Gang Yin
- Xin'an School, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, China
| | - Xiyang Wang
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, No. 1, Qianjiang Road, 230012 Hefei, Anhui, China
| | - Guoming Shen
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, No. 1, Qianjiang Road, 230012 Hefei, Anhui, China
| |
Collapse
|
|
8
|
Widjaja F, Rietjens IMCM. From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes. Biomedicines 2023; 11:2658. [PMID: 37893032 PMCID: PMC10603957 DOI: 10.3390/biomedicines11102658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
Collapse
Affiliation(s)
- Frances Widjaja
- Division of Toxicology, Wageningen University & Research, 6708 WE Wageningen, The Netherlands;
| | | |
Collapse
|
|
9
|
Halkjær SI, Lo B, Cold F, Højer Christensen A, Holster S, König J, Brummer RJ, Aroniadis OC, Lahtinen P, Holvoet T, Gluud LL, Petersen AM. Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:3185-3202. [PMID: 37346153 PMCID: PMC10280798 DOI: 10.3748/wjg.v29.i20.3185] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients’ quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as ‘gut dysbiosis’. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.
AIM To assess the efficacy and safety of FMT for the treatment of IBS.
METHODS We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.
RESULTS Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.
CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
Collapse
Affiliation(s)
- Sofie Ingdam Halkjær
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Bobby Lo
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Frederik Cold
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | | | - Savanne Holster
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Julia König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Robert Jan Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Olga C Aroniadis
- Department of Internal Medicine, Division of Gastroenterology, Renaissance School of Medicine, Stony Brook University Hospital, New York, NY 11794-8434, United States
| | - Perttu Lahtinen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti 15850, Finland
- Department of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Tom Holvoet
- Department of Gastroenterology, University Hospital Ghent, Ghent 9000, Belgium
| | - Lise Lotte Gluud
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Andreas Munk Petersen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| |
Collapse
|
|
10
|
Mahmoudi H, Hossainpour H. Application and development of fecal microbiota transplantation in the treatment of gastrointestinal and metabolic diseases: A review. Saudi J Gastroenterol 2023; 29:3-11. [PMID: 36412458 PMCID: PMC10117003 DOI: 10.4103/sjg.sjg_131_22] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically.
Collapse
Affiliation(s)
- Hassan Mahmoudi
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences; Department of Nursing and Paramedical, Nahavand School of Allied Medical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hadi Hossainpour
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
|
11
|
Procházková N, Falony G, Dragsted LO, Licht TR, Raes J, Roager HM. Advancing human gut microbiota research by considering gut transit time. Gut 2023; 72:180-191. [PMID: 36171079 PMCID: PMC9763197 DOI: 10.1136/gutjnl-2022-328166] [Citation(s) in RCA: 113] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 09/10/2022] [Indexed: 02/04/2023]
Abstract
Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet-microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
Collapse
Affiliation(s)
- Nicola Procházková
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Gwen Falony
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium
- Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
| | - Lars Ove Dragsted
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Tine Rask Licht
- National Food Institute, Technical University, Kgs. Lyngby, Denmark
| | - Jeroen Raes
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium
- Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
| | - Henrik M Roager
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| |
Collapse
|
|
12
|
Saqib Z, De Palma G, Lu J, Surette M, Bercik P, Collins SM. Alterations in fecal β-defensin-3 secretion as a marker of instability of the gut microbiota. Gut Microbes 2023; 15:2233679. [PMID: 37464450 PMCID: PMC10355691 DOI: 10.1080/19490976.2023.2233679] [Citation(s) in RCA: 2] [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: 02/20/2023] [Revised: 05/29/2023] [Accepted: 07/03/2023] [Indexed: 07/20/2023] Open
Abstract
Compositional changes in the microbiota (dysbiosis) may be a basis for Irritable Bowel Syndrome (IBS), but biomarkers are currently unavailable to direct microbiota-directed therapy. We therefore examined whether changes in fecal β-defensin could be a marker of dysbiosis in a murine model. Experimental dysbiosis was induced using four interventions relevant to IBS: a mix of antimicrobials, westernized diets (high-fat/high-sugar and high salt diets), or mild restraint stress. Fecal mouse β-defensin-3 and 16S rRNA-based microbiome profiles were assessed at baseline and during and following these interventions. Each intervention, except for mild restraint stress, altered compositional and diversity profiles of the microbiota. Exposure to antimicrobials or a high-fat/high-sugar diet, but not mild restraint stress, resulted in decreased fecal β-defensin-3 compared to baseline. In contrast, exposure to the high salt diet increased β-defensin-3 compared to baseline. Mice exposed to the mix of antimicrobials showed the largest compositional changes and the most significant correlations between β-defensin-3 levels and bacterial diversity. The high salt diet was also associated with significant correlations between changes in β-defensin-3 and bacterial diversity, and this was not accompanied by discernible inflammatory changes in the host. Thus, dietary change or antimicrobial exposure, both recognized factors in IBS exacerbations, induced marked dysbiosis that was accompanied by changes in fecal β-defensin-3 levels. We propose that serial monitoring of fecal β-defensins may serve as a marker of dysbiosis and help identify those IBS patients who may benefit from microbiota-directed therapeutic interventions.
Collapse
Affiliation(s)
- Zarwa Saqib
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Jun Lu
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Michael Surette
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Stephen Michael Collins
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
|
13
|
Lynch CMK, O’Riordan KJ, Clarke G, Cryan JF. Gut Microbes: The Gut Brain Connection. CLINICAL UNDERSTANDING OF THE HUMAN GUT MICROBIOME 2023:33-59. [DOI: 10.1007/978-3-031-46712-7_4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
14
|
Wang S, Cui J, Jiang S, Zheng C, Zhao J, Zhang H, Zhai Q. Early life gut microbiota: Consequences for health and opportunities for prevention. Crit Rev Food Sci Nutr 2022; 64:5793-5817. [PMID: 36537331 DOI: 10.1080/10408398.2022.2158451] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The gut microbiota influences many aspects of the host, including immune system maturation, nutrient absorption and metabolism, and protection from pathogens. Increasing evidences from cohort and animal studies indicate that changes in the gut microbiota early in life increases the risk of developing specific diseases early and later in life. Therefore, it is becoming increasingly important to identify specific disease prevention or therapeutic solutions targeting the gut microbiota, especially during infancy, which is the window of the human gut microbiota establishment process. In this review, we provide an overview of current knowledge concerning the relationship between disturbances in the gut microbiota early in life and health consequences later in life (e.g., necrotizing enterocolitis, celiac disease, asthma, allergies, autism spectrum disorders, overweight/obesity, diabetes and growth retardation), with a focus on changes in the gut microbiota prior to disease onset. In addition, we summarize and discuss potential microbiota-based interventions early in life (e.g., diet adjustments, probiotics, prebiotics, fecal microbiota transplantation, environmental changes) to promote health or prevent the development of specific diseases. This knowledge should aid the understanding of early life microbiology and inform the development of prediction and prevention measures for short- and long-term health disorders based on the gut microbiota.
Collapse
Affiliation(s)
- Shumin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Jingjing Cui
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Shilong Jiang
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd, Beijing, China
- PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Beijing, China
| | - Chengdong Zheng
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd, Beijing, China
- PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Beijing, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Heng Zhang
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| |
Collapse
|
|
15
|
Abstract
BACKGROUND To collect the published trials of probiotics in the treatment of diarrhea and to strictly evaluate and systematically analyze the efficacy of probiotics use for the prevention and treatment of patients with diarrhea. METHODS We searched domestic and foreign literature published between January 2016 and July 2022 to find randomized control trials that used probiotics to treat diarrhea. Only studies published in English were considered. The quality of the included literatures was assessed by using the methods provided in the Cochrane Handbook. Valid data were extracted and analyzed by meta- analysis using the Software RevMan5.2. RESULTS Total 16 trials and 1585 patients were included. The results of the meta- analysis showed that in comparison with the simple Western medicine treatment group or placebo, the added use of probiotics could improve stool frequency, stool morphology, and related irritable bowel syndrome symptoms. CONCLUSION The added use of probiotics can further improve clinical outcomes in the patients with diarrhea; however, the implementation of larger and higher quality clinical trials is necessary to verify this conclusion.
Collapse
Affiliation(s)
- Fujie Wang
- Nutritional Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Zhao
- Nutritional Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weiwei Wang
- Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianqian Dai
- Nutritional Department, Xuzhou Cancer Hospital, Xuzhou China
| | - Xianghua Ma
- Nutritional Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Xianghua Ma, Nutritional Department, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, Jiangsu, China (e-mail: )
| |
Collapse
|
|
16
|
Iribarren C, Maasfeh L, Öhman L, Simrén M. Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2022; 3:e7. [PMID: 39295774 PMCID: PMC11406401 DOI: 10.1017/gmb.2022.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/02/2022] [Accepted: 07/26/2022] [Indexed: 09/21/2024]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.
Collapse
Affiliation(s)
- Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lujain Maasfeh
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - 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, Chapel Hill, NC, USA
| |
Collapse
|
|
17
|
Alabdaljabar MS, Aslam HM, Veeraballi S, Faizee FA, Husain BH, Iqbal SM, Hashmi SK. Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease. Cureus 2022; 14:e23873. [PMID: 35530905 PMCID: PMC9076056 DOI: 10.7759/cureus.23873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2022] [Indexed: 11/18/2022] Open
Abstract
A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.
Collapse
|
|
18
|
Shobeiri P, Kalantari A, Teixeira AL, Rezaei N. Shedding light on biological sex differences and microbiota-gut-brain axis: a comprehensive review of its roles in neuropsychiatric disorders. Biol Sex Differ 2022; 13:12. [PMID: 35337376 PMCID: PMC8949832 DOI: 10.1186/s13293-022-00422-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 03/14/2022] [Indexed: 12/15/2022] Open
Abstract
Women and men are suggested to have differences in vulnerability to neuropsychiatric disorders, including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, eating disorders, including anorexia nervosa, and bulimia nervosa, neurodevelopmental disorders, such as autism spectrum disorder (ASD), and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease. Genetic factors and sex hormones are apparently the main mediators of these differences. Recent evidence uncovers that reciprocal interactions between sex-related features (e.g., sex hormones and sex differences in the brain) and gut microbiota could play a role in the development of neuropsychiatric disorders via influencing the gut-brain axis. It is increasingly evident that sex-microbiota-brain interactions take part in the occurrence of neurologic and psychiatric disorders. Accordingly, integrating the existing evidence might help to enlighten the fundamental roles of these interactions in the pathogenesis of neuropsychiatric disorders. In addition, an increased understanding of the biological sex differences on the microbiota-brain may lead to advances in the treatment of neuropsychiatric disorders and increase the potential for precision medicine. This review discusses the effects of sex differences on the brain and gut microbiota and the putative underlying mechanisms of action. Additionally, we discuss the consequences of interactions between sex differences and gut microbiota on the emergence of particular neuropsychiatric disorders.
Collapse
Affiliation(s)
- Parnian Shobeiri
- School of Medicine, Tehran University of Medical Sciences (TUMS), Children's Medical Center Hospital, Dr. Qarib St., Keshavarz Blvd, 14194, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran
| | - Amirali Kalantari
- School of Medicine, Tehran University of Medical Sciences (TUMS), Children's Medical Center Hospital, Dr. Qarib St., Keshavarz Blvd, 14194, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Antônio L Teixeira
- Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Nima Rezaei
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran.
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
19
|
Fecal Microbiota Signatures Are Not Consistently Related to Symptom Severity in Irritable Bowel Syndrome. Dig Dis Sci 2022; 67:5137-5148. [PMID: 35624331 PMCID: PMC9587953 DOI: 10.1007/s10620-022-07543-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 03/01/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent functional bowel disorder, but its pathophysiology is still unknown. Although a microbial signature associated with IBS severity has been suggested, its association with IBS severity still remains largely unknown. AIMS This study aims to assess longitudinal dynamics of fecal microbiota and short-chain fatty acids (SCFAs) in different IBS severity groups and study the association with stool pattern, diet, depression, anxiety, and quality of life (QoL). METHODS A longitudinal study was performed, including n = 91 IBS patients and n = 28 matched controls. All participants collected fecal samples for microbiota composition and SCFA analysis and completed validated questionnaires regarding IBS severity, stool pattern, depression, anxiety, and IBS-QoL at two timepoints with four weeks in-between. Diet was assessed at the first timepoint. RESULTS Over time, 36% of IBS patients changed in severity group, and 53% changed in predominant stool pattern. The largest proportion of microbiota variation was explained by the individual (R2 = 70.07%). Microbiota alpha diversity and composition, and SCFAs did not differ between IBS severity groups, nor between IBS and controls. Relative abundances of Bifidobacterium, Terrisporobacter, and Turicibacter consistently differed between IBS and controls, but not between IBS severity groups. Large dynamics over time were observed in the association of microbiota composition with questionnaire data where IBS symptom severity was associated at T1 but not at T2. CONCLUSIONS Fecal microbiota and SCFA signatures were not consistently associated with IBS severity over time, indicating the importance of repeated sampling in IBS research.
Collapse
|
|
20
|
The prevalence of disorders of the gut-brain axis in type 2 diabetes mellitus patients with metabolic dysfunction-associated fatty liver disease: an observational study. Acta Gastroenterol Belg 2021; 84:541-547. [PMID: 34965034 DOI: 10.51821/84.4.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND AND STUDY AIM Disorders of the gut-brain axis (DGBI) and metabolic dysfunction-associated liver disease (MAFLD) are frequently diagnosed and exhibit pathophysiological similarities. This study aimed to estimate the prevalence of DGBI in type 2 diabetes mellitus (T2DM) patients with MAFLD. PATIENTS AND METHODS In this single center, observational study, in adults with T2DM demographics, diabetes-related parameters and liver tests were recorded. MAFLD was defined by the presence of hepatic steatosis on imaging. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed based on Rome IV criteria. Quality of life (QOL), anxiety levels and depression levels were documented by validated questionnaires. RESULTS We included 77 patients, 44 with and 33 without steatosis. There were no significant differences in age, body mass index (BMI), waist circumference, HbA1c levels or metformin use between groups. IBS was significantly more prevalent in the liver steatosis group (9/44 vs. 2/33, p = .037), while a similar trend was observed for FD (9/35 vs. 2/31, p = .103). No differences were found in anxiety, depression and overall QOL. However, QOL subscales for health worry, food avoidance and social reaction were significantly higher in the liver steatosis group. CONCLUSIONS In otherwise comparable T2DM patients, DGBI, and especially IBS, are more prevalent in the presence of MAFLD. This difference could not be attributed to increased levels of anxiety or depression. Future research should target the underlying pathophysiological mechanisms.
Collapse
|
|
21
|
Yang F, Wu J, Ye NY, Miu J, Yan J, Liu LN, Ye B. Association of Fecal Microbiota with Irritable Bowel Syndrome-Diarrhea and Effect of Traditional Chinese Medicine for Its Management. Gastroenterol Res Pract 2021; 2021:7035557. [PMID: 34691175 PMCID: PMC8529176 DOI: 10.1155/2021/7035557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/24/2021] [Accepted: 08/28/2021] [Indexed: 12/12/2022] Open
Abstract
Changes in intestinal microbiota have been linked to the development of diarrhea predominant irritable bowel syndrome (IBS-D). In order to better elucidate the relationship between intestinal microbiota changes and IBS-D, we compared fecal microbiota of IBS-D rats and healthy control using pyrosequencing of bacterial 16S rRNA gene targeted. Furthermore, we explored the effects of different traditional Chinese medicine (TCM) on intestinal microbiota of IBS-D in dose-dependent manner. Our results showed that there was no significant difference in fecal microbial community diversity among the healthy control group, IBS-D rats and IBS-D rats treated with traditional Chinese medicine, but the fecal microbial composition at different taxonomic levels have changed among these groups. Interestingly, the weight of IBS-D rats treated with moderate doses (13.4 g/kg) of TCM increased significantly, and the diarrhea-related symptoms improved significantly, which may be related to the enrichment in Deferribacteres, Proteobacteria, Tenericutes, Lachnospiraceae, and Ruminococcaceae and the reduction in Lactobacillus in fecal samples.
Collapse
Affiliation(s)
- Fang Yang
- Department of Stomach (Gastroenterology) Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital to Nanjing University of Chinese Medicine, Nantong 226000, China
| | - Jiaqi Wu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Ning-Yuan Ye
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Jing Miu
- Nantong University, Nantong 226000, China
| | - Jing Yan
- Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Li-Na Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Bai Ye
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| |
Collapse
|
|
22
|
Hu Y, Chen F, Ye H, Lu B. Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome. Sci Rep 2021; 11:17596. [PMID: 34475489 PMCID: PMC8413334 DOI: 10.1038/s41598-021-97083-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/11/2021] [Indexed: 11/29/2022] Open
Abstract
Stress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.
Collapse
Affiliation(s)
- Yue Hu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, Zhejiang, China
| | - Fang Chen
- Department of Gastroenterology, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, Zhejiang, China
| | - Haiyong Ye
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Bin Lu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, Zhejiang, China.
| |
Collapse
|
|
23
|
Vork L, Penders J, Jalanka J, Bojic S, van Kuijk SMJ, Salonen A, de Vos WM, Rajilic-Stojanovic M, Weerts ZZRM, Masclee AAM, Pozuelo M, Manichanh C, Jonkers DMAE. Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition? Front Cell Infect Microbiol 2021; 11:639667. [PMID: 34458156 PMCID: PMC8386168 DOI: 10.3389/fcimb.2021.639667] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 06/11/2021] [Indexed: 11/13/2022] Open
Abstract
Introduction Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days. Methods Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined. Results Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this. Conclusion This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.
Collapse
Affiliation(s)
- Lisa Vork
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - John Penders
- Department of Medical Microbiology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Svetlana Bojic
- Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| | - Sander M. J. van Kuijk
- Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Anne Salonen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Willem M. de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands
| | - Mirjana Rajilic-Stojanovic
- Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| | - Zsa Zsa R. M. Weerts
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Ad A. M. Masclee
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Marta Pozuelo
- Digestive System Research Unit, University Hospital Vall d’Hebron, Barcelona, Spain
| | - Chaysavanh Manichanh
- Digestive System Research Unit, University Hospital Vall d’Hebron, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Daisy M. A. E. Jonkers
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| |
Collapse
|
|
24
|
Stevenson C, Blaauw R, Fredericks E, Visser J, Roux S. Probiotic effect and dietary correlations on faecal microbiota profiles in irritable bowel syndrome. SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION 2021. [DOI: 10.1080/16070658.2019.1697038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Cheryl Stevenson
- Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Renée Blaauw
- Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Ernst Fredericks
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
| | - Janicke Visser
- Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Saartjie Roux
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
| |
Collapse
|
|
25
|
Fuentes-Chust C, Parolo C, Rosati G, Rivas L, Perez-Toralla K, Simon S, de Lecuona I, Junot C, Trebicka J, Merkoçi A. The Microbiome Meets Nanotechnology: Opportunities and Challenges in Developing New Diagnostic Devices. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2006104. [PMID: 33719117 DOI: 10.1002/adma.202006104] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/26/2020] [Indexed: 05/15/2023]
Abstract
Monitoring of the human microbiome is an emerging area of diagnostics for personalized medicine. Here, the potential of different nanomaterials and nanobiosensing technologies is reviewed for the development of novel diagnostic devices for the detection and measurement of microbiome-related biomarkers. Moreover, the current and future landscape of microbiome-based diagnostics is defined by exploring the advantages and disadvantages of current nanotechnology-based approaches, especially in the context of developing point-of-care (PoC) devices that would meet the international guidelines known as REASSURED (Real-time connectivity; Ease of specimen collection; Affordability; Sensitivity; Specificity; User-friendliness; Rapid & robust operation; Equipment-free; and Deliverability). Finally, the strategies of the latest international scientific consortia working in this field are analyzed, the current microbiome diagnostics market are reported and the principal ethical, legal, and societal issues related to microbiome R&D and innovation are discussed.
Collapse
Affiliation(s)
- Celia Fuentes-Chust
- Nanobioelectronics and Biosensors Group, Institut Català de Nanociència i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona, 08193, Spain
| | - Claudio Parolo
- Nanobioelectronics and Biosensors Group, Institut Català de Nanociència i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona, 08193, Spain
| | - Giulio Rosati
- Nanobioelectronics and Biosensors Group, Institut Català de Nanociència i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona, 08193, Spain
| | - Lourdes Rivas
- Nanobioelectronics and Biosensors Group, Institut Català de Nanociència i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona, 08193, Spain
| | - Karla Perez-Toralla
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), SPI, Gif-sur-Yvette cedex, 91191, France
| | - Stéphanie Simon
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), SPI, Gif-sur-Yvette cedex, 91191, France
| | - Itziar de Lecuona
- Bioethics and Law Observatory -UNESCO Chair in Bioethics-Department of Medicine, University of Barcelona, Barcelona, 08007, Spain
| | - Christophe Junot
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), SPI, Gif-sur-Yvette cedex, 91191, France
| | - Jonel Trebicka
- Department of Internal Medicine I, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
- European Foundation for the Study of Chronic Liver Failure, Travesera de Gracia 11, Barcelona, 08021, Spain
| | - Arben Merkoçi
- Nanobioelectronics and Biosensors Group, Institut Català de Nanociència i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona, 08193, Spain
- ICREA, Institució Catalana de Recerca i Estudis Avançats, Pg. Lluís Companys 23, Barcelona, 08010, Spain
| |
Collapse
|
|
26
|
Constante M, De Palma G, Lu J, Jury J, Rondeau L, Caminero A, Collins SM, Verdu EF, Bercik P. Saccharomyces boulardii CNCM I-745 modulates the microbiota-gut-brain axis in a humanized mouse model of Irritable Bowel Syndrome. Neurogastroenterol Motil 2021; 33:e13985. [PMID: 32955166 DOI: 10.1111/nmo.13985] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms. METHODS Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification. KEY RESULTS Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels. CONCLUSIONS & INFERENCES Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.
Collapse
Affiliation(s)
- Marco Constante
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Jun Lu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Jennifer Jury
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Liam Rondeau
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Alberto Caminero
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
|
27
|
Shanahan ER, McMaster JJ, Staudacher HM. Conducting research on diet-microbiome interactions: A review of current challenges, essential methodological principles, and recommendations for best practice in study design. J Hum Nutr Diet 2021; 34:631-644. [PMID: 33639033 DOI: 10.1111/jhn.12868] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 01/07/2021] [Accepted: 01/19/2021] [Indexed: 12/21/2022]
Abstract
Diet is one of the strongest modulators of the gut microbiome. However, the complexity of the interactions between diet and the microbial community emphasises the need for a robust study design and continued methodological development. This review aims to summarise considerations for conducting high-quality diet-microbiome research, outline key challenges unique to the field, and provide advice for addressing these in a practical manner useful to dietitians, microbiologists, gastroenterologists and other diet-microbiome researchers. Searches of databases and references from relevant articles were conducted using the primary search terms 'diet', 'diet intervention', 'dietary analysis', 'microbiome' and 'microbiota', alone or in combination. Publications were considered relevant if they addressed methods for diet and/or microbiome research, or were a human study relevant to diet-microbiome interactions. Best-practice design in diet-microbiome research requires appropriate consideration of the study population and careful choice of trial design and data collection methodology. Ongoing challenges include the collection of dietary data that accurately reflects intake at a timescale relevant to microbial community structure and metabolism, measurement of nutrients in foods pertinent to microbes, improving ability to measure and understand microbial metabolic and functional properties, adequately powering studies, and the considered analysis of multivariate compositional datasets. Collaboration across the disciplines of nutrition science and microbiology is crucial for high-quality diet-microbiome research. Improvements in our understanding of the interaction between nutrient intake and microbial metabolism, as well as continued methodological innovation, will facilitate development of effective evidence-based personalised dietary treatments.
Collapse
Affiliation(s)
- Erin R Shanahan
- School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | | | - Heidi M Staudacher
- IMPACT (The Institute for Mental and Physical Health and Clinical Translation) Food & Mood Centre, Deakin University, Geelong, VIC, Australia
| |
Collapse
|
|
28
|
Holster S, Repsilber D, Geng D, Hyötyläinen T, Salonen A, Lindqvist CM, Rajan SK, de Vos WM, Brummer RJ, König J. Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome. Benef Microbes 2020; 12:17-30. [PMID: 33350360 DOI: 10.3920/bm2020.0010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
Collapse
Affiliation(s)
- S Holster
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - D Repsilber
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - D Geng
- Man-Technology-Environmental Research Centre, Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden
| | - T Hyötyläinen
- Man-Technology-Environmental Research Centre, Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden
| | - A Salonen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - C M Lindqvist
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - S K Rajan
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - W M de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, the Netherlands
| | - R J Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - J König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| |
Collapse
|
|
29
|
The Impact of Low-Level Iron Supplements on the Faecal Microbiota of Irritable Bowel Syndrome and Healthy Donors Using In Vitro Batch Cultures. Nutrients 2020; 12:nu12123819. [PMID: 33327501 PMCID: PMC7764926 DOI: 10.3390/nu12123819] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/30/2020] [Accepted: 12/08/2020] [Indexed: 12/14/2022] Open
Abstract
Ferrous iron supplementation has been reported to adversely alter the gut microbiota in infants. To date, the impact of iron on the adult microbiota is limited, particularly at low supplementary concentrations. The aim of this research was to explore the impact of low-level iron supplementation on the gut microbiota of healthy and Irritable Bowel Syndrome (IBS) volunteers. Anaerobic, pH-controlled in vitro batch cultures were inoculated with faeces from healthy or IBS donors along with iron (ferrous sulphate, nanoparticulate iron and pea ferritin (50 μmol−1 iron)). The microbiota were explored by fluorescence in situ hybridisation coupled with flow cytometry. Furthermore, metabolite production was assessed by gas chromatography. IBS volunteers had different starting microbial profiles to healthy controls. The sources of iron did not negatively impact the microbial population, with results of pea ferritin supplementation being similar to nanoparticulate iron, whilst ferrous sulphate led to enhanced Bacteroides spp. The metabolite data suggested no shift to potentially negative proteolysis. The results indicate that low doses of iron from the three sources were not detrimental to the gut microbiota. This is the first time that pea ferritin fermentation has been tested and indicates that low dose supplementation of iron is unlikely to be detrimental to the gut microbiota.
Collapse
|
|
30
|
Vetrani C, Maukonen J, Bozzetto L, Della Pepa G, Vitale M, Costabile G, Riccardi G, Rivellese AA, Saarela M, Annuzzi G. Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals. Acta Diabetol 2020; 57:853-860. [PMID: 32114641 DOI: 10.1007/s00592-020-01494-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 01/30/2020] [Indexed: 12/14/2022]
Abstract
AIMS Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. METHODS Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. RESULTS Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). CONCLUSIONS Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.
Collapse
Affiliation(s)
- Claudia Vetrani
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy
| | - Johanna Maukonen
- VTT Technical Research Centre of Finland, Espoo, Finland
- DuPont Nutrition and Health, Kantvik, Finland
| | - Lutgarda Bozzetto
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy
| | - Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
| | - Marilena Vitale
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy
| | - Giuseppina Costabile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy
| | - Gabriele Riccardi
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy
| | - Angela Albarosa Rivellese
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy.
- Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy.
| | - Maria Saarela
- VTT Technical Research Centre of Finland, Espoo, Finland
- South Australian Research and Development Institute, Urrbrae, Australia
| | - Giovanni Annuzzi
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 5, Sergio Pansini, 80131, Naples, Italy
| |
Collapse
|
|
31
|
Gu X, Song LJ, Li LX, Liu T, Zhang MM, Li Z, Wang P, Li M, Zuo XL. Fusobacterium nucleatum Causes Microbial Dysbiosis and Exacerbates Visceral Hypersensitivity in a Colonization-Independent Manner. Front Microbiol 2020; 11:1281. [PMID: 32733392 PMCID: PMC7358639 DOI: 10.3389/fmicb.2020.01281] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 05/19/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Microbial dysbiosis is closely associated with visceral hypersensitivity and is involved in the pathogenesis of irritable bowel syndrome (IBS), but the specific strains that play a key role have yet to be identified. Previous bioinformatic studies have demonstrated that Fusobacterium is a shared microbial feature between IBS patients and maternal separation (MS)-stressed rats. In this study, we assessed the potential role of Fusobacterium nucleatum (F. nucleatum) in the pathogenesis of IBS. Methods: Fecal samples of patients with diarrhea predominant-IBS (IBS-D) and healthy controls were obtained. An MS rat model was established to receive gavage of either F. nucleatum or normal saline. Visceral sensitivity was evaluated through colorectal distension test, and fecal microbiota was analyzed by 16S rRNA gene sequencing. F. nucleatum-specific IgA levels in fecal supernatants were assessed by western blotting. The antigen reacted with the specific IgA of F. nucleatum was identified by mass spectrometry and the construction of a recombinant Escherichia coli BL21 (DE3). Results: IBS-D patients showed a lower Shannon index and a higher abundance of Fusobacterium. The F. nucleatum-gavage was shown to exacerbate visceral hypersensitivity in MS rats, with both the F. nucleatum-gavage and MS causing a decreased Shannon index and a clear segregation of fecal microbiota. In addition, specific IgA against F. nucleatum was detected in fecal supernatants of both the F. nucleatum-gavaged rats and the IBS-D patients. The FomA protein, which is a major outer membrane protein of F. nucleatum, was confirmed to react with the specific IgA of F. nucleatum in fecal supernatants. Conclusion:Fusobacterium increased significantly in IBS-D patients, and F. nucleatum was involved in the pathogenesis of IBS by causing microbial dysbiosis and exacerbating visceral hypersensitivity in a colonization-independent manner. Meanwhile, F. nucleatum was found to induce an increase in specific secretory IgA through FomA.
Collapse
Affiliation(s)
- Xiang Gu
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Li-Jin Song
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Li-Xiang Li
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Tong Liu
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Ming-Ming Zhang
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Zhen Li
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Peng Wang
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Ming Li
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheloo College of Medicine, Shandong University, Jinan, China
| |
Collapse
|
|
32
|
Sundin J, Aziz I, Nordlander S, Polster A, Hu YOO, Hugerth LW, Pennhag AAL, Engstrand L, Törnblom H, Simrén M, Öhman L. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci Rep 2020; 10:593. [PMID: 31953505 PMCID: PMC6969101 DOI: 10.1038/s41598-020-57468-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 12/30/2019] [Indexed: 12/14/2022] Open
Abstract
Altered bacterial composition and small intestinal bacterial overgrowth (SIBO) may be associated with irritable bowel syndrome (IBS). This study aimed to determine the fecal and mucosa-associated bacterial composition along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial composition of feces, and mucosa of the duodenum and sigmoid colon was determined by 16S rRNA-amplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-associated bacterial profile was associated with IBS symptom severity and breath tests results at baseline (H2 and/or CH4 ≥ 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial composition of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-associated bacterial composition, there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.
Collapse
Affiliation(s)
- Johanna Sundin
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden.,Inst. of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Imran Aziz
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Sofia Nordlander
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden.,Inst. of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Annikka Polster
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Yue O O Hu
- Centre for Translational Microbiome Research (CTMR), Micobiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 417164, Solna, Sweden
| | - Luisa W Hugerth
- Centre for Translational Microbiome Research (CTMR), Micobiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 417164, Solna, Sweden
| | - Alexandra A L Pennhag
- Centre for Translational Microbiome Research (CTMR), Micobiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 417164, Solna, Sweden
| | - Lars Engstrand
- Centre for Translational Microbiome Research (CTMR), Micobiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 417164, Solna, Sweden
| | - Hans Törnblom
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden.,Centre for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Lena Öhman
- Inst. of Medicine, University of Gothenburg, Gothenburg, Sweden. .,Inst. of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
| |
Collapse
|
|
33
|
Berding K, Donovan SM. Dietary Patterns Impact Temporal Dynamics of Fecal Microbiota Composition in Children With Autism Spectrum Disorder. Front Nutr 2020; 6:193. [PMID: 31998741 PMCID: PMC6968728 DOI: 10.3389/fnut.2019.00193] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 12/13/2019] [Indexed: 12/12/2022] Open
Abstract
Environmental factors such as diet are known influencers on gastrointestinal (GI) microbiota variability and some diseases are associated with microbial stability. Whether microbial variability is related to symptoms of Autism Spectrum Disorder (ASD) and how diet impacts microbial stability in ASD is unknown. Herein, temporal variability in stool microbiota in relation to dietary habits in 2–7 years-old children with ASD (ASD, n = 26) and unaffected controls (CONT, n = 32) was investigated. Fecal samples were collected at baseline, 6-weeks and 6-months. Bacterial composition was assessed using 16S rRNA sequencing. Short fatty acid (SCFA) concentrations were analyzed by gas chromatography. Nutrient intake was assessed using a 3-day food diary and dietary patterns (DP) were empirically derived from a food frequency questionnaire. Social deficit scores (SOCDEF) were assessed using the Pervasive Developmental Disorder Behavior Inventory-Screening Version (PDDBI-SV). GI symptoms were assessed using the GI severity index. Overall, temporal variability in microbial structure, and membership did not differ between the groups. In children with ASD, abundances of Clostridiaceae, Streptophyta, and Clostridiaceae Clostridium, varied significantly, and concentrations of all SCFAs decreased over time. Variability in community membership was negatively correlated with median SOCDEF scores. Additionally, Clostridiales, Lactococcus, Turicibacter, Dorea, and Phascolarctobacterium were components of a more stable microbiota community in children with ASD. DP1, characterized by vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with changes in species diversity, abundance of Erysipelotricaceae, Clostridiaceae Clostridium, and Oscillospira and concentrations of propionate, butyrate, isobutyrate and isovalerate in children with ASD. DP2 characterized by fried, protein and starchy foods, “Kid's meals,” condiments, and snacks was associated with variations in microbiota structure, abundance of Clostridiaceae Clostridium, and Oscillospira and changes in all SCFA concentrations. However, no association between microbial stability and SOCDEF or GI severity scores were observed. In conclusion, microbiota composition varies over time in children with ASD, might be related to social deficit scores and can be impacted by diet. Future studies investigating the physiological effect of the changes in specific microbial taxa and metabolites are needed to delineate the impact on ASD symptomology.
Collapse
Affiliation(s)
- Kirsten Berding
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Sharon M Donovan
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States.,Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, United States.,Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, IL, United States
| |
Collapse
|
|
34
|
Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace-Fitzsimons SE, Hyland N, Clarke G, Dinan TG. The Microbiota-Gut-Brain Axis. Physiol Rev 2019; 99:1877-2013. [PMID: 31460832 DOI: 10.1152/physrev.00018.2018] [Citation(s) in RCA: 2677] [Impact Index Per Article: 446.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Collapse
Affiliation(s)
- John F. Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kenneth J. O'Riordan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Caitlin S. M. Cowan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kiran V. Sandhu
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Thomaz F. S. Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Marcus Boehme
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Martin G. Codagnone
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Sofia Cussotto
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Christine Fulling
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Anna V. Golubeva
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Katherine E. Guzzetta
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Minal Jaggar
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Caitriona M. Long-Smith
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Joshua M. Lyte
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Jason A. Martin
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Alicia Molinero-Perez
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Gerard Moloney
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Emanuela Morelli
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Enrique Morillas
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Rory O'Connor
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Joana S. Cruz-Pereira
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Veronica L. Peterson
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kieran Rea
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Nathaniel L. Ritz
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Eoin Sherwin
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Simon Spichak
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Emily M. Teichman
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Marcel van de Wouw
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Ana Paula Ventura-Silva
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Shauna E. Wallace-Fitzsimons
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Niall Hyland
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Timothy G. Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| |
Collapse
|
|
35
|
Hynönen U, Zoetendal EG, Virtala AMK, Shetty S, Hasan S, Jakava-Viljanen M, de Vos WM, Palva A. Molecular ecology of the yet uncultured bacterial Ct85-cluster in the mammalian gut. Anaerobe 2019; 62:102104. [PMID: 31562947 DOI: 10.1016/j.anaerobe.2019.102104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 09/11/2019] [Accepted: 09/23/2019] [Indexed: 12/18/2022]
Abstract
In our previous studies on irritable bowel syndrome (IBS) -associated microbiota by molecular methods, we demonstrated that a particular 16S rRNA gene amplicon was more abundant in the feces of healthy subjects or mixed type IBS (IBS-M) -sufferers than in the feces of individuals with diarrhea-type IBS (IBS-D). In the current study, we demonstrated that this, so called Ct85-amplicon, consists of a cluster of very heterogeneous 16S rRNA gene sequences, and defined six 16S rRNA gene types, a to f, within this cluster, each representing a novel species-, genus- or family level taxon. We then designed specific PCR primers for these sequence types, mapped the distribution of the Ct85-cluster sequences and that of the newly defined sequence types in several animal species and compared the sequence types present in the feces of healthy individuals and IBS sufferers using two IBS study cohorts, Finnish and Dutch. Various Ct85-cluster sequence types were detected in the fecal samples of several companion and production animal species with remarkably differing prevalences and abundances. The Ct85 sequence type composition of swine closely resembled that of humans. One of the five types (d) shared between humans and swine was not present in any other animals tested, while one sequence type (b) was found only in human samples. In both IBS study cohorts, one type (e) was more prevalent in healthy individuals than in the IBS-M group. By revealing various sequence types in the widespread Ct85-cluster and their distribution, the results improve our understanding of these uncultured bacteria, which is essential for future efforts to cultivate representatives of the Ct85-cluster and reveal their roles in IBS.
Collapse
Affiliation(s)
- Ulla Hynönen
- Department of Veterinary Biosciences, Veterinary Microbiology and Epidemiology, 66 PB, 00014, University of Helsinki, Finland.
| | - Erwin G Zoetendal
- Laboratory of Microbiology, Wageningen University & Research, 6708 PB, Wageningen, the Netherlands.
| | - Anna-Maija K Virtala
- Department of Veterinary Biosciences, Veterinary Microbiology and Epidemiology, 66 PB, 00014, University of Helsinki, Finland.
| | - Sudarshan Shetty
- Laboratory of Microbiology, Wageningen University & Research, 6708 PB, Wageningen, the Netherlands.
| | - Shah Hasan
- Department of Production Animal Medicine, University of Helsinki, Paroninkuja 20, 04920, Saarentaus, Finland.
| | - Miia Jakava-Viljanen
- Department of Veterinary Biosciences, Veterinary Microbiology and Epidemiology, 66 PB, 00014, University of Helsinki, Finland.
| | - Willem M de Vos
- Laboratory of Microbiology, Wageningen University & Research, 6708 PB, Wageningen, the Netherlands; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Finland.
| | - Airi Palva
- Department of Veterinary Biosciences, Veterinary Microbiology and Epidemiology, 66 PB, 00014, University of Helsinki, Finland.
| |
Collapse
|
|
36
|
Carson TL, Little RB, Townsend S. Preliminary feasibility for recruiting and retaining black and white females to provide fecal samples for longitudinal research. Gut Pathog 2019; 11:43. [PMID: 31462930 PMCID: PMC6710875 DOI: 10.1186/s13099-019-0324-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 08/14/2019] [Indexed: 11/24/2022] Open
Abstract
As the associations between the gut microbiota and numerous health outcomes become more evident, it is important to conduct longitudinal microbiome research to advance the field beyond the identification of associations. It is also necessary to include individuals who have historically been underrepresented in biomedical research in longitudinal microbiome studies to better understand and eliminate racial/ethnic health disparities. This paper describes our experiences in recruiting and retaining participants for an ongoing, longitudinal microbiome study for which the main results will be reported at a later time. This article provides preliminary evidence of the feasibility of recruiting and retaining a racially diverse sample of females (97% completion for invited participants) for longitudinal microbiome research.
Collapse
Affiliation(s)
- Tiffany L Carson
- 1Division of Preventive Medicine, Department of Medicine, School of Medicine, University of Alabama at Birmingham, 1720 2nd Avenue South MT 639, Birmingham, AL 35294-4410 USA.,2Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL USA
| | - Rebecca B Little
- 3Division of Preventive Medicine, Department of Medicine, School of Medicine, University of Alabama at Birmingham, 1720 2nd Avenue South MT 518K, Birmingham, AL 35294-4410 USA
| | - Sh'Nese Townsend
- 4Division of Preventive Medicine, Department of Medicine, School of Medicine, University of Alabama at Birmingham, 1720 2nd Avenue South MT 518E, Birmingham, AL 35294-4410 USA
| |
Collapse
|
|
37
|
Wang L, Alammar N, Singh R, Nanavati J, Song Y, Chaudhary R, Mullin GE. Gut Microbial Dysbiosis in the Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies. J Acad Nutr Diet 2019; 120:565-586. [PMID: 31473156 DOI: 10.1016/j.jand.2019.05.015] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 05/16/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most common functional digestive condition in the industrialized world. The gut microbiota plays a key role in disease pathogenesis. OBJECTIVE A systematic review and meta-analysis on case-control studies was conducted to determine whether there is gut microbial dysbiosis in participants with IBS in comparison with healthy controls and, if so, whether the dysbiosis pattern differs among IBS subtypes and geographic regions. METHODS This review was conducted and reported according to the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) 2000 and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines. Research articles published up to May 9, 2018 were identified through MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane Library), ClinicalTrials.gov, EMBASE, and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale. Case-control studies of participants with IBS who had undergone quantitative gut microbial stool analysis were included. The primary exposure measure of interest is log10 bacterial counts per gram of stool. Meta-analyses were performed to estimate the mean difference (MD) in gut microbiota between participants with IBS and healthy controls using the random-effects model with inverse variance in Revman 5.3 and R 3.5.1. Publication bias was assessed with funnel plots and Egger's test. Between-study heterogeneity was analyzed using Higgins I2 statistic with 95% CIs. RESULTS There were 6,333 unique articles identified; 52 qualified for full-text screening. Of these, 23 studies were included for analysis (n=1,340 participants from North America, Europe, and Asia). Overall, the studies were moderate in quality. Comparing participants with IBS to healthy controls, lower fecal Lactobacillus (MD= -0.57 log10 colony-forming unit [CFU]/g; P<0.01) and Bifidobacterium (MD= -1.04 log10CFU/g; P<0.01), higher Escherichia coli (MD=0.60 log10CFU/g; P<0.01), and marginally higher Enterobacter (MD=0.74 log10CFU/g; P=0.05). No difference was found between participants with IBS and healthy controls in fecal Bacteroides and Enterococcus (P=0.18 and 0.68, respectively). Publication bias was not observed except in Bifidobacterium (P=0.015). Subgroup analyses on participants with diarrhea-predominant and constipation-predominant IBS showed consistent results with the primary results. A subgroup analysis of Chinese studies was consistent with the primary results, except for fecal Bacteroides, which was increased in participants with IBS vs healthy controls (MD=0.29; 95% CI 0.13 to 0.46; P<0.01). Although substantial heterogeneity was detected (I2>75%) in most comparisons, the direction of the effect estimates is relatively consistent across studies. CONCLUSIONS IBS is characterized by gut microbial dysbiosis. Prospective, large-scale studies are needed to delineate how gut microbial profiles can be used to guide targeted therapies in this challenging patient population.
Collapse
|
|
38
|
Hagerty SL, Ellingson JM, Helmuth TB, Bidwell LC, Hutchison KE, Bryan AD. An Overview and Proposed Research Framework for Studying Co-Occurring Mental- and Physical-Health Dysfunction. PERSPECTIVES ON PSYCHOLOGICAL SCIENCE 2019; 14:633-645. [PMID: 31173535 PMCID: PMC6778441 DOI: 10.1177/1745691619827010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Mental- and physical-health conditions co-occur at a rate much higher than chance. Of patients who have a mental-health condition, more than half also have a physical disease, and these cases are associated with increased human suffering and societal cost. Comorbidity research to date has focused on co-occurring mental- and physical-health disorders separately, and relatively little research has examined the co-occurrence of mental- and physical-health dysfunction. In addition, even less is known about why mental- and physical-health dysfunction co-occurs or how to treat these cases. Thus, the aims of this article are to highlight the need for research at the intersection of physical- and mental-health dysfunction and to provide guidance on how to research cases of comorbidity. Toward these ends, we begin by presenting a selective overview of the possible role of biological processes in the co-occurrence of physical- and mental-health dysfunction using specific illustrative examples. Specifically, we outline how biological processes within the immune system and gastrointestinal system could underlie depression, irritable bowel syndrome, and their co-occurrence. We then advance and discuss a proposed research framework, including methodological and analytic guidance, that researchers could use when studying the phenomenon of co-occurring physical- and mental-health dysfunction.
Collapse
Affiliation(s)
- Sarah L. Hagerty
- Department of Psychology and Neuroscience, University of Colorado Boulder
| | | | - Timothy B. Helmuth
- Department of Psychology and Neuroscience, University of Colorado Boulder
| | | | - Kent E. Hutchison
- Department of Psychology and Neuroscience, University of Colorado Boulder
| | - Angela D. Bryan
- Department of Psychology and Neuroscience, University of Colorado Boulder
| |
Collapse
|
|
39
|
El-Salhy M, Hausken T, Hatlebakk JG. Increasing the Dose and/or Repeating Faecal Microbiota Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS). Nutrients 2019; 11:E1415. [PMID: 31238507 PMCID: PMC6628324 DOI: 10.3390/nu11061415] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 06/19/2019] [Accepted: 06/21/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Faecal microbiome transplantation (FMT) appears to be an effective method for treating irritable bowel syndrome (IBS) patients. However, it is not clear if a high transplant dose and/or repeating FMT are/is needed to ensure a response. The present study was undertaken to clarify this matter. METHODS Ten IBS patients who did not respond to a 30-g transplant subsequently received a 60-g transplant into the duodenum via a gastroscope. The patients provided faecal samples before and 1 month after FMT. They completed five questionnaires measuring symptoms, fatigue and quality of life at baseline and then at 2 weeks, 1 month and 3 months after FMT. The dysbiosis index (DI) was measured using the GA-map Dysbiosis Test®. RESULTS Seven patients (70%) responded to the 60-g transplant, with significant clinical improvements in the abdominal symptoms, fatigue and quality of life in 57%, 80% and 67% of these patients. The 60-g transplant also reduced the DI. CONCLUSION FMT is an effective treatment for IBS. A high-dose transplant and/or repeated FMT increase the response rate and the intensity of the effects of FMT.
Collapse
Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Box 4000, 54 09 Stord, Norway.
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway.
| |
Collapse
|
|
40
|
Abstract
In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.
Collapse
|
|
41
|
Can Gut Microbiota Composition Predict Response to Dietary Treatments? Nutrients 2019; 11:nu11051134. [PMID: 31121812 PMCID: PMC6566829 DOI: 10.3390/nu11051134] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/16/2019] [Accepted: 05/20/2019] [Indexed: 11/16/2022] Open
Abstract
Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.
Collapse
|
|
42
|
Szymaszkiewicz A, Storr M, Fichna J, Zielinska M. Enkephalinase inhibitors, potential therapeutics for the future treatment of diarrhea predominant functional gastrointestinal disorders. Neurogastroenterol Motil 2019; 31:e13526. [PMID: 30549162 DOI: 10.1111/nmo.13526] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/20/2018] [Accepted: 11/12/2018] [Indexed: 02/08/2023]
Abstract
The endogenous opioid system (EOS) is considered being a crucial element involved in the pathophysiology of irritable bowel syndrome (IBS) as it regulates gastrointestinal (GI) homeostasis through modulation of motility and water and ion secretion/absorption. Along with opioid receptors (ORs), the following components of EOS can be distinguished: 1. endogenous opioid peptides (EOPs), namely enkephalins, endorphins, endomorphins and dynorphins, and 2. peptidases, which regulate the metabolism (synthesis and degradation) of EOPs. Enkephalins, which are δ-opioid receptors agonists, induce significant effects in the GI tract as they act as potent pro-absorptive neurotransmitters. The action of enkephalins and other EOPs is limited, since EOPs are easily and rapidly inactivated by a natural metalloendopeptidase (enkephalinase/neprilysin) and aminopeptidase N. Studies show that the activity of EOPs can be enhanced by inhibition of these enzymes. In this review, we discuss the antidiarrheal and antinociceptive potential of enkephalinase inhibitors. Furthermore, our review is to answer the question whether enkephalinase inhibitors may be helpful in the future treatment of diarrhea predominant functional GI disorders.
Collapse
Affiliation(s)
- Agata Szymaszkiewicz
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Martin Storr
- Department of Medicine, Ludwig Maximilians University Munich, Munich, Germany.,Center of Endoscopy, Starnberg, Germany
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Marta Zielinska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| |
Collapse
|
|
43
|
Burns G, Carroll G, Mathe A, Horvat J, Foster P, Walker MM, Talley NJ, Keely S. Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome: A Systematic Review. Am J Gastroenterol 2019; 114:429-436. [PMID: 30839392 DOI: 10.1038/s41395-018-0377-0] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation. METHODS Seven literature databases were searched using the keywords: 'functional gastrointestinal disorder', FGID, 'functional dyspepsia', 'non-ulcer dyspepsia', 'idiopathic dyspepsia', 'irritable bowel syndrome', IBS and 'immun*'. RESULTS Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal eosinophilia in FD and increased colonic mast cells in IBS. Increases in circulating α4+β7+ gut-homing T cells appear to be linked to the pathophysiology of both FD and IBS. Studies in the area are complicated by poor phenotyping of patients into subgroups and the subtle nature of the immune activity involved in FD and IBS. CONCLUSIONS Alterations in proportions of gut-homing T lymphocytes in both FD and IBS indicate that a loss of mucosal homeostasis may drive the symptoms of FD and IBS. There is indirect evidence that Th17 responses may play a role in FGIDs, however the evidence for a Th2 immune phenotype in FD and IBS is limited. Although immune involvement is evident, large, well-characterised patient cohorts are required to elucidate the immune mechanisms driving the development of FGIDs.
Collapse
Affiliation(s)
- Grace Burns
- School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
| | - Georgia Carroll
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
- School of Medicine & Public Health, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
| | - Andrea Mathe
- School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
| | - Jay Horvat
- School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
| | - Paul Foster
- School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
| | - Marjorie M Walker
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
- School of Medicine & Public Health, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
| | - Nicholas J Talley
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
- School of Medicine & Public Health, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
| | - Simon Keely
- School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia
- Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia
| |
Collapse
|
|
44
|
Bistoletti M, Caputi V, Baranzini N, Marchesi N, Filpa V, Marsilio I, Cerantola S, Terova G, Baj A, Grimaldi A, Pascale A, Frigo G, Crema F, Giron MC, Giaroni C. Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice. PLoS One 2019; 14:e0212856. [PMID: 30794676 PMCID: PMC6386304 DOI: 10.1371/journal.pone.0212856] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 02/11/2019] [Indexed: 12/14/2022] Open
Abstract
Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF- and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity.
Collapse
Affiliation(s)
- Michela Bistoletti
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Valentina Caputi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Nicolò Baranzini
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | | | - Viviana Filpa
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Ilaria Marsilio
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Silvia Cerantola
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Genciana Terova
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Andreina Baj
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Annalisa Grimaldi
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Alessia Pascale
- Department of Drug Science, University of Pavia, Pavia, Italy
| | - Gianmario Frigo
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, Pavia, Italy
| | - Francesca Crema
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, Pavia, Italy
| | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| |
Collapse
|
|
45
|
Portincasa P, Lembo A, de Bari O, Di Palo DM, Maggio A, Cataldo I, Calamita G. The Role of Dietary Approach in Irritable Bowel Syndrome. Curr Med Chem 2019; 26:3512-3520. [PMID: 28462704 DOI: 10.2174/0929867324666170428102451] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 03/16/2017] [Accepted: 03/16/2017] [Indexed: 12/12/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most frequent gastrointestinal diseases. In IBS multiple pathophysiological mechanisms including alterations in intestinal motility, permeability, nutrient absorption, and intestinal microbiota have been implicated. Foods are commonly reported by patients to be a trigger of symptoms and therefore are likely involved in the generation of symptoms in IBS. Among all possible therapeutic options, a first-line approach to IBS is dietary education and identification of foods potentially responsible for the onset or worsening of symptoms. Dietary approaches include reduction of gas-producing foods (i.e. fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)), lactose and gluten. Further studies are required to link the ultimate role of diets in different IBS subtypes.
Collapse
Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
| | - Antony Lembo
- Department of Medicine and Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
| | - Ornella de Bari
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
| | - Domenica M Di Palo
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
| | - Anna Maggio
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", 70126, Bari, Italy
| | - Ilaria Cataldo
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", 70126, Bari, Italy
| | - Giuseppe Calamita
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", 70126, Bari, Italy
| |
Collapse
|
|
46
|
Pickard JM, Zeng MY, Caruso R, Núñez G. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev 2018; 279:70-89. [PMID: 28856738 DOI: 10.1111/imr.12567] [Citation(s) in RCA: 1060] [Impact Index Per Article: 151.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co-evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
Collapse
Affiliation(s)
- Joseph M Pickard
- Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA
| | - Melody Y Zeng
- Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA
| | - Roberta Caruso
- Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA
| | - Gabriel Núñez
- Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA
| |
Collapse
|
|
47
|
Wen W, Zhang H, Shen J, Wei L, Shen S. Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol. Medicine (Baltimore) 2018; 97:e12661. [PMID: 30290648 PMCID: PMC6200478 DOI: 10.1097/md.0000000000012661] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 09/13/2018] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.
Collapse
|
|
48
|
Chang C. Short-course therapy for diarrhea-predominant irritable bowel syndrome: understanding the mechanism, impact on gut microbiota, and safety and tolerability of rifaximin. Clin Exp Gastroenterol 2018; 11:335-345. [PMID: 30288076 PMCID: PMC6160288 DOI: 10.2147/ceg.s167031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by abdominal pain that occurs with defecation or alterations in bowel habits. Further classification is based on the predominant bowel habit: constipation-predominant IBS, diarrhea-predominant IBS (IBS-D), or mixed IBS. The pathogenesis of IBS is unclear and is considered multifactorial in nature. GI dysbiosis, thought to play a role in IBS pathophysiology, has been observed in patients with IBS. Alterations in the gut microbiota are observed in patients with small intestinal bacterial overgrowth, and overgrowth may occur in a subset of patients with IBS. The management of IBS includes therapies targeting the putative factors involved in the pathogenesis of the condition. However, many of these interventions (eg, eluxadoline and alosetron) require long-term, daily administration and have important safety considerations. Agents thought to modulate the gut microbiota (eg, antibiotics and probiotics) have shown potential benefits in clinical studies. However, conventional antibiotics (eg, neomycin) are associated with several adverse events and/or the risk of bacterial antibiotic resistance, and probiotics lack uniformity in composition and consistency of response in patients. Rifaximin, a nonsystemic antibiotic administered as a 2-week course of therapy, has been shown to be safe and efficacious for the treatment of IBS-D. Rifaximin exhibits a favorable benefit-to-harm ratio when compared with daily therapies for IBS-D (eg, alosetron and tricyclic antidepressants), and rifaximin was not associated with the emergence of bacterial antibiotic resistance. Thus, short-course therapy with rifaximin is an appropriate treatment option for IBS-D.
Collapse
Affiliation(s)
- Christopher Chang
- New Mexico VA Health Care System, Division of Gastroenterology and Hepatology, Albuquerque, NM, USA,
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA,
| |
Collapse
|
|
49
|
Gargari G, Taverniti V, Gardana C, Cremon C, Canducci F, Pagano I, Barbaro MR, Bellacosa L, Castellazzi AM, Valsecchi C, Tagliacarne SC, Bellini M, Bertani L, Gambaccini D, Marchi S, Cicala M, Germanà B, Dal Pont E, Vecchi M, Ogliari C, Fiore W, Stanghellini V, Barbara G, Guglielmetti S. Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome. Environ Microbiol 2018; 20:3201-3213. [PMID: 29749705 DOI: 10.1111/1462-2920.14271] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 05/07/2018] [Indexed: 12/16/2022]
Abstract
Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.
Collapse
Affiliation(s)
- Giorgio Gargari
- Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy
| | - Valentina Taverniti
- Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy
| | - Claudio Gardana
- Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy
| | - Cesare Cremon
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Filippo Canducci
- Dipartimento di biotecnologie e scienze della vita, Università degli Studi dell'Insubria, Varese, Italy
| | - Isabella Pagano
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Maria Raffaella Barbaro
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Lara Bellacosa
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Anna Maria Castellazzi
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Chiara Valsecchi
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Sara Carlotta Tagliacarne
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Massimo Bellini
- Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy
| | - Lorenzo Bertani
- Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy
| | - Dario Gambaccini
- Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy
| | - Santino Marchi
- Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy
| | - Michele Cicala
- Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | | | | | - Maurizio Vecchi
- Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato, Milanese, Italy
| | - Cristina Ogliari
- Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato, Milanese, Italy
| | | | - Vincenzo Stanghellini
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy
| | - Simone Guglielmetti
- Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy
| |
Collapse
|
|
50
|
Seura T, Yoshino Y, Fukuwatari T. The Relationship between Habitual Dietary Intake and Gut Microbiota in Young Japanese Women. J Nutr Sci Vitaminol (Tokyo) 2018; 63:396-404. [PMID: 29332901 DOI: 10.3177/jnsv.63.396] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Recent studies have shown that dietary content affects the health of the host by changing the gut microbiota. However, little is known about the association of microbiota composition with habitual diet in Japanese people. Here, we aimed to clarify the relationship between the fecal microbiota and habitual dietary intake of micronutrients, macronutrients and food groups in healthy young Japanese women. Analysis of fecal microbiota was performed by the terminal restriction fragment length polymorphism (T-RFLP) method, and a dietary survey was conducted over three consecutive days using a weighed food record method. T-RFLP pattern analysis divided the subjects into two clusters, where cluster A group had a high relative abundance of Bacteroides and Clostridium cluster IV, and cluster B group had a high relative abundance of Bifidobacterium and Lactobacillales. Cluster A group also had lower intakes of iron and vitamin K and higher intakes of mushrooms and snacks than cluster B group. Analysis of Spearman rank correlations found several significant relationships between fecal microbiota and intake of nutrients and food groups. Bifidobacterium was correlated with iron intake, and Clostridium cluster XI was negatively correlated with intakes of cholesterol and eggs. These results suggest that dietary habits may strongly affect Bifidobacterium, Bacteroides and Clostridium abundance in the gut microbiota of young Japanese women. This is the first study to show relationships between fecal microbiota and habitual dietary intake in Japanese people. Accumulation of results from similar studies will help to elucidate the relationships between dietary intake and diseases in Japanese people.
Collapse
Affiliation(s)
- Takahiro Seura
- Department of Sports and Health Sciences, Faculty of Health and Medical Sciences, Aichi Shukutoku University.,Department of Nutrition, School of Human Cultures, The University of Shiga Prefecture
| | - Yoko Yoshino
- Department of Nutritional Management, Faculty of Nutritional Science, Sagami Women's University
| | - Tsutomu Fukuwatari
- Department of Nutrition, School of Human Cultures, The University of Shiga Prefecture
| |
Collapse
|