scholarly journals Propionate Fermentative Genes of the Gut Microbiome Decrease in Inflammatory Bowel Disease

2021 ◽  
Vol 10 (10) ◽  
pp. 2176
Author(s):  
Juan Manuel Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz

Changes in the gut microbiome have been associated with inflammatory bowel disease. A protective role of short chain fatty acids produced by the gut microbiota has been suggested as a causal mechanism. Nevertheless, multi-omic analyses have failed to identify a clear link between changes in specific taxa and disease states. Recently, metagenomic analyses unveiled that gut bacterial species have a previously unappreciated genomic diversity, implying that a geno-centric approach may be better suited to identifying the mechanisms involved. Here, we quantify the abundance of terminal genes in propionate-producing fermentative pathways in the microbiome of a large cohort of healthy subjects and patients with inflammatory bowel disease. The results show that propionate kinases responsible for propionate production in the gut are depleted in patients with Crohn’s disease. Our results also indicate that changes in overall species abundances do not necessarily correlate with changes in the abundances of metabolic genes, suggesting that these genes are not part of the core genome. This, in turn, suggests that changes in strain composition may be as important as changes in species abundance in alterations of the gut microbiome associated with pathological conditions.

Author(s):  
Farhad Hatami ◽  
Emma Beamish ◽  
Albert Davies ◽  
Rachael Rigby ◽  
Frank Dondelinger

Abstract The human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current approaches for detecting microbiome associations are limited by relying on specific measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome. In this work, we develop a novel hierarchical Bayesian model for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We perform extensive simulation studies and show that our method allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease, and a study of associations between diet and the gut microbiome in mice. We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.


Author(s):  
Oliver Grundmann

The human gut microbiome has garnered much attention over the past two decades with important discoveries linking it to human health and disease. The commensal bacterial flora evolves due to the influence of a number of factors including diet, pathogen exposure, environmental toxicants, disease states, and a challenged microenvironment that requires balancing with the host itself. However, the composition of bacterial species can impact and contribute to the development of local and systemic inflammation. Among the factors attributed to intestinal inflammation are dysbiosis caused by pathogenic bacteria, following decreased host immunity or loss of intestinal barrier function. Dysbiosis can also be triggered by antibiotic therapy or the use of other medications that allow for colonisation of pathogenic bacteria, such as proton pump inhibitors. The imbalance with commensal bacteria leads to the generation of proinflammatory mediators and a reduction of host immune defences, due to a lack of short-chain fatty acid generation needed for energy production to maintain barrier and immune function. The initially localised inflammation results in further dysbiosis as former commensal bacteria are able to breach the barrier and cause systemic immune responses. Low-grade systemic inflammation is a hallmark of inflammatory bowel disease. Because a specific dysbiosis is common in patients with inflammatory bowel disease, it can serve as an early diagnostic marker in its development. Furthermore, faecal microbiome transplants have shown promising benefits in patients with ulcerative colitis and Crohn’s disease.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Barbara Olednzki ◽  
Vanni Bucci ◽  
Caitlin Cawley ◽  
Ana Maldonado-Contreras

Abstract Background and Aims The inflammatory bowel disease-anti-inflammatory diet (IBD-AID) is a whole food diet designed to favor the development of an anti-inflammatory microbiome and to assist with remission in patients suffering from inflammatory bowel disease (IBD). Herein, we evaluated the effect of the IBD-AID on the gut microbiome and defined the impact of specific foods on bacteria depleted in IBD patients, as well as the clinical response to the IBD-AID. Methods A single-arm, pre-post intervention trial was performed. After a baseline period, a dietary intervention was initiated. We collected stool and blood samples throughout the study and assessed dietary intake and disease severity. We applied advanced computational approaches to define and model complex interactions between the diet, microbiota, and response to the IBD-AID. Results A dense dataset comprising 553 dietary records and 340 stool samples was compiled from 22 subjects participating in the study. The IBD-AID favored bacteria that are normally depleted in IBD cohorts and capable of producing short-chain fatty acids (SCFAs). Consumption of non-starchy vegetables, nuts, and seeds positively correlated with increased abundance of SCFA-producing bacteria, including Roseburia hominis, Eubacterium eligens,and Faecalibacterium prausnitzii. Half of the subjects completing the intervention with high diet adherence (>60%) reported a positive clinical response to the IBD-AID, with a subset of bacterial species predicting diet-induced reduction of symptoms with 67% accuracy. After the intervention, subjects also exhibited a reduction of circulating inflammatory markers. Conclusions The IBD-AID favors the growth of SCFA-producing bacteria that are depleted during IBD dysbiosis. The microbiome signatures emerging after the IBD-AID can predict response to the diet.


2020 ◽  
Author(s):  
Farhad Hatami ◽  
Emma Beamish ◽  
Rachael Rigby ◽  
Frank Dondelinger

AbstractMotivationThe human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current statistical techniques for microbiome association studies are limited by relying on measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome.ResultsIn this work, we develop a novel Bayesian multi-task approach for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We apply our method to simulated data and show that it allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease (Beamish, 2017), and a study of associations between diet and the gut microbiome in mice (Turnbaugh et al., 2009). We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.AvailabilityOur method is implemented using the R interface to the Stan Hamiltonian Monte Carlo sampler. Software for running our methods is available at https://github.com/FrankD/MicrobiomeGlobalAssociations.Contactf.dondelinger@lancaster.ac.uk


Cureus ◽  
2021 ◽  
Author(s):  
Nso Nso ◽  
Akwe Nyabera ◽  
Mahmoud Nassar ◽  
Mohsen S Alshamam ◽  
Vikram Sumbly ◽  
...  

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


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