Alistipes finegoldii promotes the development of inflammatory bowel disease: effect and mechanism

Abstract:

Objective To study the effect of Alistipes finegoldii (AF) on inflammatory bowel disease (IBD) and the underlying mechanism.Methods Six-week-old male C57BL/6J mice were administrated with streptomycin for three days and then randomly assigned into the control, phosphate buffered saline (PBS), and AF groups. Mice were administrated with AF suspension (1×10⁹ CFU, 200 μL per mouse) or PBS by gavage for two weeks, followed by drinking of the water containing 2.5% dextran sulfate sodium (DSS) for one week for the modeling of colitis. The weight loss fraction percentage, fecal characteristics, blood fecesstools, and colon length were determined. The colon tissue was stained with hematoxylin-eosin for the scoring of histopathological changes, and feces samples were collected at the beginning and end of the experiment for sequencing of 16S rRNA gene amplicons at the beginning and end of the experiment. The mRNA levels of colon tissue-associated intestinal barrier proteins and inflammatory mediators were determined by qPCR.Results The mice in the AF group had severer disease conditions than those in the PBS group regarding the weight loss percentage, disease activity index, colon shortening, and histopathological score. Compared with the PBS group, the AF group showed down-regulated mRNA levels of occludin and claudin 5 and up-regulated mRNA level of interleukin (IL)-17A. The AF group had lower alpha diversity of intestinal flora than the PBS group, and the beta diversity showed significant differences between AF and PBS groups. The linear discriminant analysis effect size (LEfSe) results revealed that the significantly differential bacteria between AF and PBS groups were Bacilli, Erysipelotrichales, Erysipelotichaceae, Odoribacter, Marinifilaceae, Dubosiella, and Dubosiella newyorkensis.Conclusion AF promotes the secretion of inflammatory mediators, impairs the permeability of the intestinal mucosa, and alters the structure and diversity of the intestinal flora, thereby promoting the development of IBD.

Key words:inflammatory bowel disease;intestinal flora;Alistipes finegoldii;intestinal barrier