Treatment with a Monoclonal Anti-IL-12p40 Antibody Induces Substantial Gut Microbiota Changes in an Experimental Colitis Model

Gastroenterology Research and Practice
Josué Castro-MejíaThomas L Holm

Abstract

Background and Aim. Crohn's disease is associated with gut microbiota (GM) dysbiosis. Treatment with the anti-IL-12p40 monoclonal antibody (12p40-mAb) has therapeutic effect in Crohn's disease patients. This study addresses whether a 12p40-mAb treatment influences gut microbiota (GM) composition in mice with adoptive transfer colitis (AdTr-colitis). Methods. AdTr-colitis mice were treated with 12p40-mAb or rat-IgG2a or NaCl from days 21 to 47. Disease was monitored by changes in body weight, stool, endoscopic and histopathology scores, immunohistochemistry, and colonic cytokine/chemokine profiles. GM was characterized through DGGE and 16S rRNA gene-amplicon high-throughput sequencing. Results. Following 12p40-mAb treatment, most clinical and pathological parameters associated with colitis were either reduced or absent. GM was shifted towards a higher Firmicutes-to-Bacteroidetes ratio compared to rat-IgG2a treated mice. Significant correlations between 17 bacterial genera and biological markers were found. The relative abundances of the RF32 order (Alphaproteobacteria) and Akkermansia muciniphila were positively correlated with damaged histopathology and colonic inflammation. Conclusions. Shifts in GM distribution were observed ...Continue Reading

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Citations

Oct 31, 2018·Critical Reviews in Food Science and Nutrition·Qixiao ZhaiWei Chen
Mar 14, 2020·International Journal of Molecular Sciences·Masafumi NodaMasanori Sugiyama

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Methods Mentioned

BETA
flow cytometry
electrophoresis
PCR
biopsies
Illumina sequencing

Software Mentioned

GraphPad
MEICS
Quantitative Insight Into Microbial Ecology ( QIIME
ANOSIM
GraphPad Prism
Visiopharm Integrator System ( VIS

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