Lactobacillus johnsonii N5 from heat stress-resistant pigs improves gut mucosal immunity and barrier in dextran sodium sulfate-induced colitis
摘要Developing effective strategies to prevent diarrhea and associated-gut disorders in mammals has gained great significance.Owing to the many health benefits provided by the commensal microbiota of the intestinal tract,such as against environmental perturbation,we explored the host phenotype-associated microbes and their probiotic potential.Based on the observations that the chronic heat stress-exposed weaned piglets present as heat stress-susceptible(HS-SUS)or heat stress-resistant(HS-RES)in-dividuals,we confirmed the phenotypic difference between the two on growth performance(P<0.05),diarrhea index(P<0.001),intestinal heat shock protein 70(HSP70)regulation(P<0.01),and inflam-matory responses(P<0.01).By comparing the gut microbiome using 16S rRNA gene sequencing and KEGG functional analysis,we found that Lactobacillus johnsonii exhibited significantly higher relative abundance in the HS-RES piglets than in the HS-SUS ones(P<0.05).Further experiments using a mouse model for chemical-induced inflammation and intestinal injury demonstrated that oral administration of a representative L.johnsonii N5(isolated from the HS-RES piglets)ameliorated the clinical and histo-logical signs of colitis while suppressing intestinal pro-inflammatory cytokines TNF-a and IL-6 produc-tion(P<0.05).We found that N5 treatment enhanced tight junction proteins ZO-1 and occludin and cytoprotective HSP70 levels under physiological condition and restored their mucosal expressions in colitis(P<0.05).In support of the high production of the anti-inflammatory cytokine IL-10,N5 promoted the intestinal Peyer's patches MHCII+and CD103+dendritic cell populations(P<0.05),increased the regulatory T(Treg)cell numbers(P<0.05),and decreased the Th17 population and its IL-17a production under physiological condition and during colitis(P<0.01).Our results shed light on understanding the interaction between commensal Lactobacillus and the host health,and provide L.johnsonii N5 as an alternative to antibiotics for preventing diarrhea and intestinal diseases.
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