Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects

Abstract

Lactobacillus rhamnosus GG (LGG), the well‐characterized human‐derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase‐3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)‐producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase‐3−GSDMEa pyroptosis is initiated by the species‐specific recognition of SpaC by TLR4ba, which accounts for the species‐specificity of the SpaC‐inducing intestinal pyroptosis in zebrafish. The observed pyroptosis‐driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host‐specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

Effects of Dietary Supplementation with Endogenous Probiotics Bacillus subtilis on Growth Performance, Immune Response and Intestinal Histomorphology of Juvenile Rainbow Trout (Oncorhynchus mykiss)

“…For this reason, researchers have begun to pay more attention to host-associated probiotics and their application within aquaculture in recent years [18]. Zhang et al reported on the safety issues when using probiotics obtained from other species in aquaculture, and suggested developing probiotic strains specific to each species rather than directly extending probiotic strains isolated from one species to others [19]. In our previous study, a Bacillus subtilis strain RT-BS07 was isolated from the gut of healthy juvenile rainbow trout.…”