title: Intestinal Microbiota-Derived GABA Mediates Interleukin-17 Expression during EnterotoxigenicEscherichia coliInfection.
abstract: Intestinal microbiota has critical importance in pathogenesis of intestinal infection; however, the role of intestinal microbiota in intestinal immunity during enterotoxigenicEscherichia coli(ETEC) infection is poorly understood. The present study tested the hypothesis that the intestinal microbiota is associated with intestinal interleukin-17 (IL-17) expression in response to ETEC infection. Here, we found ETEC infection induced expression of intestinal IL-17 and dysbiosis of intestinal microbiota, increasing abundance of γ-aminobutyric acid (GABA)-producingLactococcus lactissubsp.lactis. Antibiotics treatment in mice lowered the expression of intestinal IL-17 during ETEC infection, while GABA orL. lactissubsp.lactisadministration restored the expression of intestinal IL-17.L. lactissubsp.lactisadministration also promoted expression of intestinal IL-17 in germ-free mice during ETEC infection. GABA enhanced intestinal IL-17 expression in the context of ETEC infection through activating mechanistic target of rapamycin complex 1 (mTORC1)-ribosomal protein S6 kinase 1 (S6K1) signaling. GABA-mTORC1 signaling also affected intestinal IL-17 expression in response toCitrobacter rodentiuminfection and in drug-induced model of intestinal inflammation. These findings highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases.
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ren
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiao
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Bie
authors.initials: B
authors.lastname: Tan
authors.affiliation: Chongqing Key Laboratory of Forage and Herbivorce, College of Animal Science and Technology, Southwest University , Chongqing , China.
authors.forename: Nengzhang
authors.initials: N
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Forage and Herbivorce, College of Animal Science and Technology, Southwest University , Chongqing , China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medicine Science, Third Military Medical University , Chongqing , China.
authors.forename: Benhua
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medicine Science, Third Military Medical University , Chongqing , China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medicine Science, Third Military Medical University , Chongqing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Biomedical Translational Research Institute, Jinan University , Guangzhou , China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Animal Science, Texas A&M University , College Station, TX , USA.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University , Manhattan, KS , USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hardwidge
authors.affiliation: National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, China; College of Animal Science, South China Agricultural University, Guangzhou, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
keywords: ETEC; GABA; IL-17; Lactococcus lactis; intestinal microbiota; mTORC1