Lactobacillusalleviates intestinal epithelial barrier function through GPR43-mediated M2 macrophage polarization

Abstract

Lactobacillusspecies have excellent abilities to reduce intestinal inflammation and enhance gut barrier function. This study elucidated the potential mechanisms through which Lactobacillusmitigates lipopolysaccharide (LPS)-induced intestinal injury from the perspective of macrophage-intestinal epithelial cell interactions. Lactobacillusintervention improved the histopathological score; elevated ZO-1 and Occludin protein production; reduced CD16⁺ cell numbers; diminished IL-1β, IL-6, and TNF-α levels; decreased inducible nitric oxide synthase (iNOS) expression; increased CD163⁺ cell numbers; elevated IL-10 concentration; and increased arginase-1 (Arg1) expression in LPS-challenged piglets. Lactobacilluspretreatment also altered the colonic microbiota, thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets. Compared with those in the LPS group, sodium butyrate (SB) pretreatment decreased IL-1β, IL-6 and TNF-α secretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages. The SB-pretreated macrophages reduced the protein expression of TLR4, MyD88, and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells. Moreover, GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells. This study demonstrated that Lactobacillusimproves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.

Keywords

Lactobacillus / Butyric acid / GPR43 / Macrophage / Gut barrier

References

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