Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with Crohn's disease
Abstract
BACKGROUND & AIMS
The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. Therefore, we aimed to assess if alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease.
METHODS
We utilized the Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using urinary fractional excretion ratio of lactulose to mannitol (LMR). Microbiome composition was assessed by sequencing fecal 16S rRNA. The cohort was divided into a discovery cohort (n=2,472) and a validation cohort (n=655). A regression model was used to assess microbial associations with LMR. A Random Forest classifier algorithm was performed to assess microbial community contribution to barrier function.
RESULTS
Subjects with impaired barrier function (LMR>0.025) had reduced alpha-diversity (Chao1 index, p=4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, R2=0.001, p=1.0e-3) compared to subjects with LMR≤0.025. When taxa were assessed individually, we identified eight genera and 52 microbial pathways associated with LMR>0.025 (q<0.05). Four genera (decreased prevalence of Adlercreutzia, Clostridia UCG 014, and Clostridium sensu stricto 1 and increased abundance of Colidextribacter) and eight pathways (including…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 2,472 participants or records.
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