Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Hong‐Ling Zhang
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Da‐Hai Yang
State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai China
Qiang Hao
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Hong‐Wei Yang
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
De‐Long Meng
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Willem Meindert de Vos
Laboratory of Microbiology Wageningen University and Research Wageningen Netherlands
Le‐Luo Guan
Faculty of Land and Food Systems The University of British Columbia Vancouver Canada
Shu‐Bin Liu
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Tsegay Teame
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Chen‐Chen Gao
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Chao Ran
Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Ya‐Lin Yang
Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Yuan‐Yuan Yao
Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Qian‐Wen Ding
Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
Zhi‐Gang Zhou
China‐Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
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.
