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IntroductionInflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD.MethodsFecal and serum samples were collected from patients with IBD (n=55) and age- and sex-matched healthy controls (n=55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing.ResultsIgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Veillonella and Enterobacteriaceae, as well as against specific Lachnospiraceae bacteria, including Coprococcus and Dorea (all P<0.001), and to Ruminococcus gnavus-like bacteria (P<0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the Lachnospiraceae members Roseburia and Blautia, to Faecalibacterium, as well as to Bacteroides. Patients with IBD showed more IgG-coating of Streptococcus, Lactobacillus, and Lactococcus bacteria compared to healthy controls (all P<0.05). No differences in IgG-coated bacterial fractions were observed between Crohn’s disease and ulcerative colitis, between active or non-active disease, nor between different disease locations.ConclusionThe IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria.

Aims: We performed a randomized, placebo-controlled trial, RIBOGUT, to study the effect of 2 weeks supplementation with either 50 or 100 mg/d of riboflavin on (i) Faecalibacterium prausnitzii abundance, (ii) gut microbiota composition, (iii) short-chain fatty acid (SCFA) profiles, and (iv) the satiety and gut hormones. Results: Neither dose of riboflavin, analyzed separately, impacted the abundance of F. prausnitzii , and only minor differences in SCFA concentrations were observed. However, combining the results of the 50 and 100 mg/d groups showed a significant increase in butyrate production. While the gut bacterial diversity was not affected by riboflavin supplementation, the complexity and stability of the bacterial network were enhanced. Oral glucose tolerance tests showed a trend of increased plasma insulin concentration and GLP-1 after 100 mg/d supplementation. Innovation: Dietary supplements, such as vitamins, promote health by either directly targeting host physiology or indirectly via gut microbiota modulation. Here, we show for the first time that riboflavin intervention changes the activity of the microbiota. The butyrate production increased after intervention and although the composition did not change significantly, the network of microbial interactions was enforced. Conclusion: This RIBOGUT study suggests that oral riboflavin supplementation promotes butyrate production in the absence of major shifts in gut microbiota composition. Identifier: NCT02929459.