Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in...

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Autores principales:	Siyuan Sun, Xiuxiu Xu, Ling Liang, Xiaoli Wang, Xue Bai, Lanping Zhu, Qijin He, Huixi Liang, Xin Xin, Li Wang, Chenxi Lou, Xiaocang Cao, Xin Chen, Bingzhi Li, Bangmao Wang, Jingwen Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ulcerative colitis lactic acid Saccharomyces cerevisiae pyroptosis gut microbiota Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/7e28a7eea9b44092838795fb1dd74773
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spelling	oai:doaj.org-article:7e28a7eea9b44092838795fb1dd747732021-11-30T19:17:23ZLactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota1664-322410.3389/fimmu.2021.777665https://doaj.org/article/7e28a7eea9b44092838795fb1dd747732021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.777665/fullhttps://doaj.org/toc/1664-3224Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.Siyuan SunXiuxiu XuLing LiangXiaoli WangXue BaiLanping ZhuQijin HeHuixi LiangXin XinLi WangChenxi LouXiaocang CaoXin ChenBingzhi LiBangmao WangJingwen ZhaoFrontiers Media S.A.articleulcerative colitislactic acidSaccharomyces cerevisiaepyroptosisgut microbiotaImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ulcerative colitis lactic acid Saccharomyces cerevisiae pyroptosis gut microbiota Immunologic diseases. Allergy RC581-607
spellingShingle	ulcerative colitis lactic acid Saccharomyces cerevisiae pyroptosis gut microbiota Immunologic diseases. Allergy RC581-607 Siyuan Sun Xiuxiu Xu Ling Liang Xiaoli Wang Xue Bai Lanping Zhu Qijin He Huixi Liang Xin Xin Li Wang Chenxi Lou Xiaocang Cao Xin Chen Bingzhi Li Bangmao Wang Jingwen Zhao Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
description	Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.
format	article
author	Siyuan Sun Xiuxiu Xu Ling Liang Xiaoli Wang Xue Bai Lanping Zhu Qijin He Huixi Liang Xin Xin Li Wang Chenxi Lou Xiaocang Cao Xin Chen Bingzhi Li Bangmao Wang Jingwen Zhao
author_facet	Siyuan Sun Xiuxiu Xu Ling Liang Xiaoli Wang Xue Bai Lanping Zhu Qijin He Huixi Liang Xin Xin Li Wang Chenxi Lou Xiaocang Cao Xin Chen Bingzhi Li Bangmao Wang Jingwen Zhao
author_sort	Siyuan Sun
title	Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
title_short	Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
title_full	Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
title_fullStr	Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
title_full_unstemmed	Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota
title_sort	lactic acid-producing probiotic saccharomyces cerevisiae attenuates ulcerative colitis via suppressing macrophage pyroptosis and modulating gut microbiota
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7e28a7eea9b44092838795fb1dd74773
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Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota

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