@article{e88f48740e9e424d89f5c4ed7378a888,
title = "Dietary-protein sources modulate host susceptibility to Clostridioides difficile infection through the gut microbiota",
abstract = "Clostridioides difficile causes nosocomial antibiotic-associated diarrhea on a global scale. Susceptibility to C. difficile infection (CDI) is influenced by the composition and metabolism of gut microbiota, which in turn are affected by diet. However, the mechanism underlying the interplay between diet and gut microbiota that modulates susceptibility to CDI remains unclear. Here, we show that a soy protein diet increases the mortality of antibiotic-treated, C. difficile-infected mice while also enhancing the intestinal levels of amino acids (aas) and relative abundance of Lactobacillus genus. Indeed, Ligilactobacillus murinus-mediated fermentation of soy protein results in the generation of aas, thereby promoting C. difficile growth, and the process involves the anchored cell wall proteinase PrtP. Thus, mutual interaction between dietary protein and the gut microbiota is a critical factor affecting host susceptibility to CDI, suggesting that dietary protein sources can be an important determinant in controlling the disease.",
keywords = "CP: Microbiology, Clostridioides difficile infection, Lactobacillus, amino acids, dietary protein sources, proteinase, soy protein",
author = "Kyosuke Yakabe and Seiichiro Higashi and Masahiro Akiyama and Hiroshi Mori and Takumi Murakami and Atsushi Toyoda and Yuta Sugiyama and Shigenobu Kishino and Kenji Okano and Akiyoshi Hirayama and Aina Gotoh and Shunyi Li and Takeshi Mori and Takane Katayama and Jun Ogawa and Shinji Fukuda and Koji Hase and Kim, {Yun Gi}",
note = "Funding Information: This work was supported by research grants from JSPS KAKENHI ( JP21gm1010009 to S.F. and JP17H05068 and JP20H03490 to Y.-G.K.); AMED ( JP18gm6010004h0003 to Y.-G.K.); JST ERATO ( JPMJER1902 to S.F.); the Food Science Institute Foundation (to S.F.); and Yakult Bio-Science Foundation (to Y.-G.K.). This work was funded by Meiji Holdings Co., Ltd. (Y.-G.K.). The graphical abstract and experimental protocols were created using BioRender.com . Funding Information: This work was supported by research grants from JSPS KAKENHI (JP21gm1010009 to S.F. and JP17H05068 and JP20H03490 to Y.-G.K.); AMED (JP18gm6010004h0003 to Y.-G.K.); JST ERATO (JPMJER1902 to S.F.); the Food Science Institute Foundation (to S.F.); and Yakult Bio-Science Foundation (to Y.-G.K.). This work was funded by Meiji Holdings Co. Ltd. (Y.-G.K.). The graphical abstract and experimental protocols were created using BioRender.com. Y.-G.K. conceived the study and designed the experiments; K.Y. performed most of the experiments; S.H. performed fecal aa analysis; A.H. and S.F. performed CE-TOFMS-based metabolome analysis; H.M. T.M. and A.T. performed L. murinus whole-genome sequencing; Y.S. S.K. K.O. and J.O. generated the L. murinus ΔprtP strain; A.G. S.L. T.M. T.K. and K.H. provided resources; K.Y. M.A. and Y.-G.K. analyzed the data; K.Y. and Y.-G.K. wrote the manuscript with contributions from all the authors. Y.-G.K. supervised the project. S.H. was an employee of the Co-Creation Center, Meiji Holdings Co. Ltd. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = sep,
day = "13",
doi = "10.1016/j.celrep.2022.111332",
language = "English",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}