Abstract
This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients in clinical remission. Microbial compositional differences were analyzed according to the trough level of infliximab (TLI) and mucosal healing (MH) status. 16S rRNA gene-based microbiome profiling was performed on 10 and 74 fecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. Fecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks, immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months. There were no significant changes in microbial composition, species richness, or diversity indices between 1W and 7W. However, 7W samples from the patients with TLI ≥ 5 μg/mL showed an increased species richness compared with patients with TLI < 5 μg/mL, and patients with MH showed increased diversity compared with non-MH patients. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LEfSe analysis identified differential composition of Faecalibacterium prausnitzii group according to TLI and MH. In conclusion, these results suggest the potential of fecal microbiota as a response indicator.
Highlights
Inflammatory bowel disease (IBD) is characterized by dysregulated mucosal immune responses to the intestinal microbiota [1], the pathogenesis is not fully understood
Our study found that fecal microbiota in patients with therapeutic trough level of infliximab (TLI) and mucosal healing (MH) showed increased bacterial diversity, richness, and relative abundance of F. prausnitzii group, compared with the patients with subtherapeutic TLI and non-mucosal healing (non-MH)
It is well established that bacterial diversity and richness of the intestinal microbiota are reduced in active IBD patients [7,23], whereas dysbiosis is diminished in inactive IBD patients after infliximab treatment [4,5,6,7,8]
Summary
Inflammatory bowel disease (IBD) is characterized by dysregulated mucosal immune responses to the intestinal microbiota [1], the pathogenesis is not fully understood. Several patients reported symptom aggravation 1–2 weeks prior to subsequent infliximab administrations, and these symptoms recovered within 1–2 weeks after infliximab infusion In this context, if the composition and diversity of intestinal microbiota changed meaningfully during the 8-week infliximab infusion cycle, this fluctuation of symptoms might be explained with the microbial changes according to serum infliximab level. We evaluated changes in the intestinal microbiota during an 8-week infliximab infusion cycle in IBD patients, to suggest an appropriate timing of fecal sampling for the evaluation of gut microbial composition and diversity. The microbial profile of patients with infliximab maintenance therapy according to emerging therapeutic targets, such as trough level of infliximab (TLI) and mucosal healing (MH), were analyzed to identify potential compositional biomarkers for IBD
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