Gut microbiome structure and metabolic activity in inflammatory bowel disease
By Eric A. Franzosa, Alexandra Sirota-Madi, J. Ávila-Pacheco, Nadine Fornelos, Henry J. Haiser, S. Reinker, Tommi Vatanen, A. B. Hall, Himel Mallick, Lauren J. McIver and 17 more. Nature Microbiology, 2018
1,686 citations recorded by the source corpus.
The inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome—the molecular interface between host and microbiota—are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic ‘guilt by association’ (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome–metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets. Using metabolomics and shotgun metagenomics on stool samples from individuals with and without inflammatory bowel disease, metabolites, microbial species and genes associated with disease were identified and validated in an independent cohort.
Subfields: Gastroenterology, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/d47d5e723c0b3c71904f5829af2e5972131bc0d2
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
In Physiology
Citations in the corpus
- Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota (2023, background): “Studies focusing on the effects of high-fiber diets, such as Mediterranean, vegetarian, and vegan diets, on patients affected by IBD, resulted in improvements in microbiome outcomes (i cre se in alpha diversity, increase in specific microbial population, etc.), in laboratory exams (reduction in C-re”
- Using clusterProfiler to characterize multiomics data (2024, neutral): “Perform enrichment analysis of differential metabolites cpd_enrich_result - compareCluster(geneClusters = de_cpd, fun = "enrichKEGG", organism = "cpd") To conduct an enrichment analysis using the KEGG Compound database (CPD), which aids in characterizing biological processes relevant to the differe”
- Interaction between microbiota and immunity in health and disease (2020, background): “These include a reduced bacterial diversity and marked shifts in abundance of certain bacterial taxa, including decreased abundance of Bacteroides, Firmicutes, Clostridia, Lactobacillus, Ruminococcaceae and increased abundance of Gammaproteobacteria and Enterobacteriaceae,(149,150), coupled with alt”