Healthy first-degree relatives of children and adolescents with inflammatory bowel disease had intestinal dysbiosis and an altered intestinal metabolome that correlated with one another and with the disease state, researchers reported in the November issue of Cellular and Molecular Gastroenterology and Hepatology.
These findings suggest the existence of a “high-risk microbiome/metabolome” that may increase susceptibility to inflammatory bowel disease (IBD), Jonathan Jacobs, MD, of the University of California, Los Angeles, reported with his associates. Among the healthy relatives with dysbiosis, nearly one-third also had elevated levels of fecal calprotectin, a marker of intestinal inflammation that has been previously reported in family members of patients with ulcerative colitis, the researchers noted. “If validated, prospective identification of [high-risk individuals] creates the opportunity to prevent disease development by targeting the dysbiosis and/or its metabolic consequences in the intestine,” they wrote.
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ulcerative colitis
Participants in the study fell into one of two “operational taxonomic units” based on their microbial communities, the researchers said. The second taxonomic unit not only was associated with IBD, “but irrespective of disease status, had lower microbial diversity and characteristic shifts in microbial composition, including increased Enterobacteriaceae, consistent with dysbiosis.” Among 21 families in the study, 19 had at least one member in this group. Furthermore, tests of an independent pediatric cohort revealed this same taxonomic group characterized by low microbial diversity and associated with IBD.
Participants also fell into two distinct metabotypes, one of which was associated with IBD and had increased levels of bile acids and amino acid derivatives previously linked to Crohn’s disease, as well as elevated levels of taurine, tryptophan, serinyl tryptophan, and adrenic acid, an omega-6 fatty acid, the researchers said. Taxonomic units and metabolic groups correlated highly with one another among both IBD patients and healthy relatives (P = 3 × 10-8), suggesting a “functional relationship between the microbiome and the metabolome,” the investigators said. Additionally, although most healthy relatives had normal fecal calprotectin levels, those in the second operational taxonomic unit had about sixfold greater odds of elevated calprotectin, compared with those in the first group (P = .05).
“The existence of an IBD-associated operational taxonomic unit type and metabotype in healthy relatives suggests that dysbiosis with its associated metabolic products may be a preexisting trait that precedes the acquisition of [inflammatory bowel] disease,” the investigators concluded. “Validating this interpretation will require prospective longitudinal studies to assess the incidence of IBD in individuals stratified by operational taxonomic type, metabotype, and calprotectin, and to assess the stability of operational taxonomic unit types and metabotypes across time and diet.”
The research was supported by the Helmsley Charitable Trust, the Crohn’s and Colitis Foundation of America, the Fineberg Foundation, the United States Public Health Service, the National Institutes of Health, the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, the European Union, and the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics. The investigators had no conflicts of interest.