Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment

By Xochitl C. Morgan, Timothy L. Tickle, Harry Sokol, Dirk Gevers, K. Devaney, D. Ward, Joshua A Reyes, Samir A. Shah, N. LeLeiko, S. Snapper and 5 more. Genome Biology, 2012

2,570 citations recorded by the source corpus.

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.

Subfields: Genetics, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/060fbb7ae458fa71a477ff22f825b6c06344b773

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Infectious Diseases

In Molecular Biology

Citations in the corpus

Host genetic variation impacts microbiome composition across human body sites (2015, background): “uncovering the genic composition and metabolic capacity of the microbiome [1, 48].”
New evidences on the altered gut microbiota in autism spectrum disorders (2017, background): “The evidence that the taxa belonging to the Clostridium cluster XVIII and the putative proinflammatory Escherichia/Shigella [41, 42] positively correlated with the constipation status of the subjects as well as their enrichment in constipated autistic subjects supports the hypothesis that GI problem”
Disentangling Interactions in the Microbiome: A Network Perspective (2016, background): “For example, dysbiosis of the human gut microbiome is associated with a wide range of pathologies, including diarrhea [4], diabetes [5], colorectal cancer [6], inflammatory bowel [14_TD$DIFF]disease [7], irritable bowel syndrome [8], and obesity [9].”
Probiotics, gut microbiota, and their influence on host health and disease (2017, background): “Diseases in which the strict anaerobic population is decreased normally involve physiological conditions in which inflammation and oxidative stress are present [100].”
The Intestinal Microbiome in Early Life: Health and Disease (2014, background): “stool microbiome genes involved in complex carbohydrate metabolism were diminished and may result in decreased utilization of these substrates in the gut (186).”
Colonocyte metabolism shapes the gut microbiota (2018, background): “Dysbiosis in the colon is commonly associated with an increased abundance of facultative anaerobic bacteria (28, 29), which is observed in individuals undergoing antibiotic therapy (30), consuming a high-fat Western-style diet (31, 32), or suffering from inflammatory bowel disease (33), colorectal c”
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “Intestinal inflammation can lead to an altered composition of gut mi crobiota, known as dysbiosis, that is associated with functional changes in the microbial transcriptome, proteome or met abolome (132-134).”
Multivariable association discovery in population-scale meta-omics studies (2021, methodology): “Unlike MaAsLin 1’s single-model framework based on applications of arcsine square root-transformed linear model following Total Sum Scaling (TSS) normalization [15,16], MaAsLin 2 has evaluated and combined the best set of analysis steps to facilitate high-precision association discovery in microbiom”
Computational meta'omics for microbial community studies (2013, background): “…on host–microbiome interactions with the immune system like-wise include concrete host-based mechanisms by which homeostasis is maintained (Ivanov et al , 2009; Hooper et al , 2012) and by which disease-associated dysbiosis develops (Turnbaugh et al , 2010; Kau et al , 2011; Morgan et al , 2012).”
The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes (2015, positive): “This analysis was performed using multivariate association with linear models (MaAsLin) (Morgan et al., 2012), an additive general linear model with boosting that can capture the effects of a parameter of interest while deconfounding the effects of other metadata.”
A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients (2017, background): “Additionally, the gut microbiome in IBD shows dysbiosis characterized by increased abundance of functional pathways involved in the microbial response to oxidative stress [5].”