Microbiome and Metabolic Features Tied to IBD Treatment Response

The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success.

Gastroenterologists at the Massachusetts General Hospital (Cambridge, MA, USA) and their colleagues collected over time from nearly 200 individuals with moderate to severe Crohn's disease or ulcerative colitis. The scientists used a combination of metagenomic sequencing, serum metabolomics, and serum proteomics to search for biomarkers coinciding with remission after treatment with biologic therapy, particularly anti-cytokine or anti-integrin therapy.

The team reported that specific sets of immune or gut microbiome features associated with clinical remission after 14 weeks or a year of treatment with each of the drug types, compared to the samples collected before these therapies began for the 77 ulcerative colitis patients and 108 Crohn's disease cases included in the study. Nearly half of the participants had clinical remission within the first 14 weeks of treatment, while another 22 patients reached remission within 52 weeks of follow up.

When it came to the therapies targeting the tumor necrosis factor (TNF) inflammatory cytokine or interleukin (IL)-12 or IL-23 cytokines, for example, the investigators found that treatment responses were more common in the patients with relatively rich gut microbial communities prior to treatment. They also saw an over-representation of microbes linked to dihydroxylation processes that convert primary bile acids to secondary bile acids in the IBD patients who responded well to these treatments, results supported by their tandem mass spectrometry-based serum metabolite analyses.

Similarly, IBD remission after anti-cytokine treatment appeared to coincide with the presence of microbial diversity-linked immune proteins circulating in the blood, the team reported, which could be detected based on telltale proteomic signatures in blood serum samples. The investigators detected a distinct set of gut microbial, blood serum proteomic, and metabolomic patterns in the IBD patients who responded to, or reached remission on, an anti-integrin treatment that targets leukocyte trafficking processes.

The authors concluded that their results suggest that features found in the stool and blood may help for predicting responses to existing therapies, while providing a better look at disease pathology and progression, which may ultimately point to potentially targetable pathways for new drug development or probiotic tools for preventing inflammation. The study was published on July 22,2021 in the journal Cell Host and Microbe.

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Massachusetts General Hospital