Abstract

Bacteroides fragilis, one of the potential next-generation probiotics, has been demonstrated to alleviate inflammation-associated diseases. In this study, we compare the anti-inflammatory effects of six Bacteroides fragilis strains on systemic inflammation and link their strain-specific characteristics, both physiologically and genetically, to their function. A lipopolysaccharide (LPS)-induced systemic inflammation model in mice was used as an in vivo model to compare the effects of different B. fragilis strains. Short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The in vitro immunomodulatory properties were evaluated in LPS-stimulating RAW264.7 cell lines. Orthologous gene clusters were compared using OrthoVenn2. The results indicate a strain-specific in vitro anti-inflammatory effect. Effective strains induce higher colon SCFAs in vivo and interleukin-10 (IL-10) production in vitro. Comparative genomic analysis showed that the SCFA-inducing strains possess three genes relating to carbohydrate metabolism (GH2, GH35 families) and binding and transportation (SusD), all of which are associated with niche fitness and expansion. IL-10-inducing strains share a highly similar gene, wbjE, which may result in a distinct O-antigen structure of LPS and influence their immunomodulatory properties. B. fragilis is strain-specific against LPS-induced systemic inflammation in mice. The beneficial effects of a specific strain may be attributed to its SCFA and IL-10 inducing abilities. Strain-specific potential genes can be excavated to link these differences.

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