Dock2 affects the host susceptibility to Citrobacter rodentium infection through regulating gut microbiota

Yuan Xie,Lu Xie,Zhiping Liu,Jun Chen,Tiansheng He,Bing Wu

doi:10.1186/s13099-021-00449-x

Yuan Xie, Lu Xie + Show 4 more

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https://doi.org/10.1186/s13099-021-00449-x

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Abstract

BackgroundDysregulated gut microbiota is one of major pathogenic factors in the development of colitis. Dock2 acts as a guanine nucleotide exchange factor (GEF) and activates small G protein RAC1. Our previous study showed that, compared to wild type (WT) mice, Dock2−/− mice were more susceptible to colitis induced by Citrobacter rodentium infection. However, it is not clear whether gut microbiota affects the host susceptibility to enteric bacterial infection in Dock2−/− mice.ResultsIn this study, we demonstrated that Dock2 regulated the gut microbiota and affected the host susceptibility to C. rodentium infection by co-housing, fecal microbiota transfer and antibiotic treatment methods. Microbiota analysis by 16 S rRNA gene sequencing showed that Dock2 increased the abundance of prevotellaceae-NK3B31-group and Lactobacillus but decreased that of Helicobacter.ConclusionsThese results suggest that Dock2 regulates the composition of gut microbiota and affects the host susceptibility to C. rodentium infection.

Highlights

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), causes chronic relapsing inflammatory disorders in genetically susceptible individuals [1, 2]
These results indicated that wild type (WT) and Dedicator of cytokinesis 2 (Dock2)−/− mice had differences in composition of gut microbiota, and WT mice might obtain gut microbiota from Dock2−/− mice by co-housing, which increased their susceptibility to C. rodentium infection
Consistent with these findings, we showed that Dock2 deficiency has significant consequences on the composition of gut microbiota characterized by the decrease in Prevotellaceae-NK3B31group and Lactobacillus and the increase in Helicobacter, which was linked to the enhanced vulnerability to C. rodentium infection

Summary

Introduction

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), causes chronic relapsing inflammatory disorders in genetically susceptible individuals [1, 2]. C. rodentium is a gram-negative bacterium in the intestine, which can induce intestinal proliferation and inflammation Different from another commonly used colitis model which is induced by innate immune response by the treatment of dextran sodium sulfate, C. rodentium infection induces host immune response involving with both innate and adaptive immunity, which is more similar to IBD patients [4]. Our previous study showed that, compared to wild type (WT) mice, Dock2−/− mice were more susceptible to colitis induced by Citrobacter rodentium infection. It is not clear whether gut microbiota affects the host susceptibility to enteric bacterial infection in Dock2−/− mice

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