Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease.

BACKGROUND: The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease. METHODS: We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts. RESULTS: At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline. CONCLUSIONS: High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.

We studied absolute and relative abundances of fecal microbiota in relation to response to induction therapy with infliximab in pediatric inflammatory bowel disease. We discovered that a high absolute abundance of anti-inflammatory Bifidobacteriales at baseline associated with response.

Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease.

BACKGROUND AND AIMS: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate. SUBJECTS AND METHODS: We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected. RESULTS: Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn´s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD. CONCLUSIONS: Fecal microbiota in CLD is different from that of healthy subjects or Crohn´s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.

The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α.

Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.