Lactobacillus intervention facilitates gut barrier function, decreases corticosterone and ameliorates social behavior in LPS-exposed offspring.

Probiotic therapy such as Lactobacillus has emerged as a promising adjuvant therapy for autism, but its mechanism remains elusive. To elucidate the ameliorative effects of Lactobacillus in autism, we employed a rat model of autism by lipopolysaccharide (LPS) injection during pregnancy. After birth, Lactobacillus reuteri (L.reuteri) or Lactobacillus rhamnosus (LGG) was orally administered to the offspring for three weeks. Our findings indicated that Lactobacillus effectively ameliorated the social deficits and anxiety in offspring. Besides, treatment with Lactobacillus significantly increased butyric acid and decreased propionic acid concentrations in the LPS-exposed group. It also enhanced the colonic barrier integrity by promoting the expression levels of ZO-1, Occludin, and Claudin4 in the LPS offspring. RNA sequencing analysis revealed that differentially expressed genes of L.reuteri or LGG groups were enriched in pathways associated with inflammation, HPA axis, and reactive oxygen species metabolism (of which NADPH oxidase1, NOX1, is the pivotal gene in the pathway). Further validation of the sequencing data revealed that two Lactobacillus species could reduce inflammation cytokines levels, inhibit HPA axis hormone secretion, increase antioxidant levels, and suppress the NF-kB/NOX1 pathway of the LPS-exposed rats. In the H2O2-induced oxidative stress model of Caco-2 cells, pretreatment with L.reuteri, LGG, or NF-kB inhibitors also significantly increased the cellular antioxidant levels, decreased the activation of NF-kB/NOX1 pathway, and improved barrier function. In general, L.reuteri and LGG administration could improve social behavior, enhance the colonic barrier function, reduce pro-inflammatory factor levels, and inhibit the HPA axis in LPS-exposed rats. Meanwhile, two Lactobacillus species also ameliorated oxidative stress in the colon and Caco-2 cells, likely mediated through inhibition of NF-kB/NOX1 signaling pathway.