AUTHOR=Ling Na , Zhang Xiyan , Forsythe Stephen , Zhang Danfeng , Shen Yizhong , Zhang Jumei , Ding Yu , Wang Juan , Wu Qingping , Ye Yingwang 

TITLE=Bacteroides fragilis ameliorates Cronobacter malonaticus lipopolysaccharide-induced pathological injury through modulation of the intestinal microbiota

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.931871

DOI=10.3389/fimmu.2022.931871

ISSN=1664-3224

ABSTRACT=<p><italic>Cronobacter</italic> has attracted considerable attention due to its association with meningitis and necrotizing enterocolitis (NEC) in newborns. Generally, lipopolysaccharide (LPS) facilitates bacterial translocation along with inflammatory responses as an endotoxin; however, the pathogenicity of <italic>Cronobacter</italic> LPS and the strategies to alleviate the toxicity were largely unknown. In this study, inflammatory responses were stimulated by <uri xlink:href="http://www.baidu.com/link?url=rWZJVQ-G07obrxEvZ2a1IItiyB4FHCqmHIqX8wwAXJurAHG8hFjYb8ln6TZyvGSRS24ugF9JDQ4E2HqxAx59riyGWejRr1l09C2RSHKxyGfYCBusW8k-oGHtfkt8tA8F" xmlns:xlink="http://www.w3.org/1999/xlink">intraperitoneal injection</uri> of <italic>Cronobacter malonaticus</italic> LPS into Sprague–Dawley young rats. Simultaneously, <italic>Bacteroides fragilis</italic> NCTC9343 were continuously fed through gavage for 5 days before or after injection of <italic>C. malonaticus</italic> LPS to evaluate the intervention effect of <italic>B. fragilis</italic>. We first checked the morphological changes of the ileum and colon and the intestinal microbiota and then detected the generation of inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) and the expression of Toll-like receptor 4 (TLR4), occludin, claudin-4, and iNOs. The results indicated that <italic>C</italic>. <italic>malonaticus</italic> LPS exacerbated intestinal infection by altering gut microbe profile, tight junction protein expression, and releasing inflammatory factors in a time- and dose-dependent manner. Intriguingly, treatment with <italic>B. fragilis</italic> obviously diminished the pathological injuries and expression of TLR4 caused by <italic>C. malonaticus</italic> LPS while increasing gut microbes like <italic>Prevotella</italic>-9. We note that <italic>Shigella</italic>, <italic>Peptoclostridium</italic>, and <italic>Sutterella</italic> might be positively related to <italic>C</italic>. <italic>malonaticus</italic> LPS infection, but <italic>Prevotella</italic>-9 was negatively correlated. The results suggested that the intestinal microbiota is an important target for the prevention and treatment of pathogenic injuries induced by <italic>C. malonaticus</italic> LPS.</p>