Combined analysis of metagenomic data revealed consistent changes of gut microbiome structure and function in inflammatory bowel disease

Author(s):  
Yangliu Xia ◽  
Jingjing Wang ◽  
Xiaojie Fang ◽  
Tongyi Dou ◽  
Lijuan Han ◽  
...  
Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 4
Author(s):  
Lara Hart ◽  
Charlotte M. Verburgt ◽  
Eytan Wine ◽  
Mary Zachos ◽  
Alisha Poppen ◽  
...  

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.


2017 ◽  
Author(s):  
Thomas Sharpton ◽  
Svetlana Lyalina ◽  
Julie Luong ◽  
Joey Pham ◽  
Emily M. Deal ◽  
...  

AbstractThe gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regards to function. To investigate microbiome mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where dampened TGF-β signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including dampened acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, lipooligosaccharide transporter abundance diverges prior to immune activation, indicating that it could be a pre-disease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundance of particular taxa, including several species ofBacteroides, correlate with immune activation. These discoveries were enabled by our use of generalized linear mixed effects models to test for differences in longitudinal profiles between healthy and diseased mice while accounting for the distributions of taxon and gene counts in metagenomic data. These findings demonstrate that longitudinal metagenomics is useful for discovering potential mechanisms through which the gut microbiome becomes altered in IBD.ImportanceIBD patients harbor distinct microbial communities with different functional capabilities compared to healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading up to disease onset. By performing weekly metagenomic sequencing and mixed effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study is novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e041733
Author(s):  
Paul Moayyedi ◽  
Glenda MacQueen ◽  
Charles N Bernstein ◽  
Stephen Vanner ◽  
Premysl Bercik ◽  
...  

IntroductionGut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.Methods and analysisThis 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.Ethics and disseminationApproval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number:NCT03131414


2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Jonas Halfvarson ◽  
Colin J. Brislawn ◽  
Regina Lamendella ◽  
Yoshiki Vázquez-Baeza ◽  
William A. Walters ◽  
...  

2013 ◽  
Vol 154 (38) ◽  
pp. 1512-1523
Author(s):  
András Arató

In the last decades our knowledge has been enormously broadened about the structure and function of the gut associated lymphoid system. It was recognized how intricate and finely tuned connection exists between the gut bacterial flora and the intestinal mucosa. This subtle balance ensures mucosal homeostasis, which has a key role in organ defence against pathogens. However, at the same time this system makes possible the development of oral tolerance toward the commensals and the food antigens. In case of any disturbances in this finely tuned process, immunmediated intestinal disorders may easily develop. The first part of this paper reviews the structure and function of the mucosal immune system, while the second part surveys the pathogenesis, diagnosis and therapy of coeliac disease, inflammatory bowel disease and cow’s milk allergy induced enteropathy. Orv. Hetil., 2013, 154, 1512–1523.


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