Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy

Abstract

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn’s disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).

Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches

“…The main signs of gut microbiome changes in IBD patients receiving biologic treatment include an increment in SCFA-producing bacteria and a decrease in Escherichia and Enteroccocus [ 49 ]. The gut microbiota composition in patients treated with adalimumab (TNF-α inhibitor) shifted towards a microbiota typical for healthy individuals [ 50 ]. Moreover, differences in patient gut microbiota before and during biologic therapy may affect the period of remission.…”

Mucosal host–microbe interactions associate with clinical phenotypes in inflammatory bowel disease

“…In addition, we observe a Ruminococcaceae-UCG-002-associated network of genes involved in (peroxisomal) fatty acid oxidation and lipotoxicity, which are inversely associated with these bacteria in patients using TNF-α-antagonists. Interestingly, multiple studies have observed that Ruminococcaceae increase after anti-TNF therapy in patients with CD and UC [73,[75][76][77]. One of these studies specifically identified an association between the Ruminococcaceae_UCG-002 group and responsiveness to TNF-α-antagonists, albeit not in relation to host gene expression patterns [75].…”

“…The inverse associations between Ruminococcaceae_UCG_002 and genes involved in (peroxisomal) fatty acid oxidation in patients using TNF-α-antagonists might reflect a beneficial therapeutic modulation, i.e. a reduction of fatty acid oxidation and lipotoxicity, and possibly even attenuation of microbiota-induced intestinal inflammation [73][74][75][76][77][78][79][80][81][82][83][84][85]. CentrLCC-network analyses were performed to characterize altered mucosal host-microbe interactions between different patient phenotypes.…”

Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease

“…However, treatment failures with anti-TNF-α are common [ 94 ], and there have been concerns with potential complications from therapy, including an increased risk of malignancies [ 95 ]. Interestingly, a recent study correlated the responsiveness of IBD patients to TNF-α therapy with bacteria diversity, but not fungal diversity, in the faecal microbiome [ 96 ].…”