Lactobacillus Modulates Intestinal Epithelial Proliferation to Alleviate S. Typhimurium Induced Mucosal Barrier Damage Through Wnt/β-Catenin Pathway
35 Pages Posted: 28 Aug 2018More...
The influence of intestinal microbiota, such as Lactobacillus, on intestinal mucosa, especially in the proliferation of intestinal stem cells, are still incompletely understood. In this study, intestinal organoids and mice were used to explore proliferation effect of Lactobacillus on intestinal epithelial through modulation of Wnt/βcatenin pathway. The study demonstrated that L. acidophilus increased survival ratio of mice infected with S. typhimurium, as well as reduced TNF-α secretion and S. typhimurium colonization in feces. S. typhimurium infection caused crypt hyperplasia with enhancement of PCNA cells and crypt length remarkably with over-expression of β-catenin, which was also remitted by L. acidophilus. Similar protective effects of L. acidophilus on inhibiting intestinal inflammation and crypt hyperplasia induced by S. typhimurium was also observed in intestinal organoids model by alleviating TNF-α secretion and β-catenin over-expression. S. typhimurium infection induced hyperplasia of UEA-1 goblet cells and Lysozyme Paneth cells both in mice and organoids to defend against pathogen invasion through exploiting TLR2 and TLR4. However, L. acidophilus ameliorated over-activation of TLRs and Wnt/β-catenin pathway to impair excessive expansion of goblet cells and Paneth cells induced by S. typhimurium. Our study implied that L. acidophilus protected intestinal mucosa against S. typhimurium infection by moderate modulating Wnt/β-catenin pathways to affect intestinal epithelial proliferation.
Funding Statement: This study was supported by the National Natural Science Foundation of China (31502024), National Key Research and Development Program of China (2018YFD0500600), Jiangsu Agriculture Science and Technology Innovation Fund (JASTIF, CX1066) and PAPD.
Declaration of Interests: There are no conflicts of interest (financial, professional or personal) related to this manuscript.
Ethics Approval Statement: All animal experiments were carried out in strict accordance with the regulations in the Guide for the Care and Use of Laboratory Animals issued by the Ministry of Science and Technology of the People's Republic of China. All efforts were made to minimize suffering. The animal protocol was approved by the University of Nanjing Agriculture University Committee on Animal Resources Committee.
Keywords: Lactobacillus; S. typhimurium; Intestinal Epithelial; Proliferation; Intestinal Stem Cells
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