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Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome

Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota a...

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Autores principales: Wu, Jingjing, Man, Da, Shi, Ding, Wu, Wenrui, Wang, Shuting, Wang, Kaicen, Li, Yating, Yang, Liya, Bian, Xiaoyuan, Wang, Qiangqiang, Li, Lanjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788567/
https://www.ncbi.nlm.nih.gov/pubmed/36558471
http://dx.doi.org/10.3390/nu14245311
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author Wu, Jingjing
Man, Da
Shi, Ding
Wu, Wenrui
Wang, Shuting
Wang, Kaicen
Li, Yating
Yang, Liya
Bian, Xiaoyuan
Wang, Qiangqiang
Li, Lanjuan
author_facet Wu, Jingjing
Man, Da
Shi, Ding
Wu, Wenrui
Wang, Shuting
Wang, Kaicen
Li, Yating
Yang, Liya
Bian, Xiaoyuan
Wang, Qiangqiang
Li, Lanjuan
author_sort Wu, Jingjing
collection PubMed
description Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota and metabolome after short-term (2 weeks) or long-term (20 weeks) IF and therefore clarify the potential mechanisms by which IF ameliorates DSS-induced colitis in a murine model. Thirty-two C57BL/6 male mice were equally divided into four groups and underwent IF intervention for 2 weeks (SIF group, n = 8), 20 weeks (LIF group, n = 8), or were allowed free access to food for 2 weeks (SAL group, n = 8) or 20 weeks (LAL group, n = 8). The thirty-two C57BL/6 male mice were accepted for the diet intervention of 2 weeks of IF or fed ad libitum. Colitis was induced by drinking 2% DSS for 7 days. Our findings showed that short-term IF prominently elevates the abundance of Bacteroides, Muibaculum and Akkermansia (p < 0.001, p < 0.001, p < 0.001, respectively), and decreased the abundance of Ruminiclostridium (p < 0.05). Long-term IF, however, decreased the abundance of Akkermansia and obviously increased the abundance of Lactobacillus (p < 0.05, p < 0.001, respectively). Metabolites mainly associated with nucleoside, carbohydrate, amino acid, bile acid, fatty acid, polyol, steroid and amine metabolism were identified in the faeces using untargeted GC/MS. In particular, inosine was extremely enriched after short-term IF and long-term IF (p < 0.01, p < 0.01, respectively); butyrate, 2-methyl butyric acid and valeric acid were significantly decreased after short-term IF (p < 0.001, p < 0.001, p < 0.01, respectively); and 2-methyl butyric acid was significantly increased after long-term IF (p < 0.001). The abundance of lithocholic acid (LCA), one of the secondary bile acids, increased significantly after short-term and long-term IF based on UPLC–MS/MS (p < 0.001, p < 0.5, respectively). Of note, IF markedly mitigated DSS-induced acute colitis symptoms and down-regulated pro-inflammatory cytokines IL-1α, IL-6, keratinocyte-derived chemokine (KC) and G-CSF levels in the serum (p < 0.01, p < 0.001, p < 0.05, p < 0.001, respectively). Furthermore, a correlation analysis indicated that the disease activity index (DAI) score and serum levels of IL-1α, IL-6, KC, and G-CSF were negatively correlated with the relative abundance of Akkermansia and the faecal metabolites LCA and inosine. This study confirmed that IF altered microbiota and reprogramed metabolism, which was a promising development in the attempt to prevent DSS-induced colitis. Moreover, our findings provide new insights regarding the correlations among the mucosal barrier dysfunction, metabolome, and microbiome.
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spelling pubmed-97885672022-12-24 Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome Wu, Jingjing Man, Da Shi, Ding Wu, Wenrui Wang, Shuting Wang, Kaicen Li, Yating Yang, Liya Bian, Xiaoyuan Wang, Qiangqiang Li, Lanjuan Nutrients Article Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota and metabolome after short-term (2 weeks) or long-term (20 weeks) IF and therefore clarify the potential mechanisms by which IF ameliorates DSS-induced colitis in a murine model. Thirty-two C57BL/6 male mice were equally divided into four groups and underwent IF intervention for 2 weeks (SIF group, n = 8), 20 weeks (LIF group, n = 8), or were allowed free access to food for 2 weeks (SAL group, n = 8) or 20 weeks (LAL group, n = 8). The thirty-two C57BL/6 male mice were accepted for the diet intervention of 2 weeks of IF or fed ad libitum. Colitis was induced by drinking 2% DSS for 7 days. Our findings showed that short-term IF prominently elevates the abundance of Bacteroides, Muibaculum and Akkermansia (p < 0.001, p < 0.001, p < 0.001, respectively), and decreased the abundance of Ruminiclostridium (p < 0.05). Long-term IF, however, decreased the abundance of Akkermansia and obviously increased the abundance of Lactobacillus (p < 0.05, p < 0.001, respectively). Metabolites mainly associated with nucleoside, carbohydrate, amino acid, bile acid, fatty acid, polyol, steroid and amine metabolism were identified in the faeces using untargeted GC/MS. In particular, inosine was extremely enriched after short-term IF and long-term IF (p < 0.01, p < 0.01, respectively); butyrate, 2-methyl butyric acid and valeric acid were significantly decreased after short-term IF (p < 0.001, p < 0.001, p < 0.01, respectively); and 2-methyl butyric acid was significantly increased after long-term IF (p < 0.001). The abundance of lithocholic acid (LCA), one of the secondary bile acids, increased significantly after short-term and long-term IF based on UPLC–MS/MS (p < 0.001, p < 0.5, respectively). Of note, IF markedly mitigated DSS-induced acute colitis symptoms and down-regulated pro-inflammatory cytokines IL-1α, IL-6, keratinocyte-derived chemokine (KC) and G-CSF levels in the serum (p < 0.01, p < 0.001, p < 0.05, p < 0.001, respectively). Furthermore, a correlation analysis indicated that the disease activity index (DAI) score and serum levels of IL-1α, IL-6, KC, and G-CSF were negatively correlated with the relative abundance of Akkermansia and the faecal metabolites LCA and inosine. This study confirmed that IF altered microbiota and reprogramed metabolism, which was a promising development in the attempt to prevent DSS-induced colitis. Moreover, our findings provide new insights regarding the correlations among the mucosal barrier dysfunction, metabolome, and microbiome. MDPI 2022-12-14 /pmc/articles/PMC9788567/ /pubmed/36558471 http://dx.doi.org/10.3390/nu14245311 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Jingjing
Man, Da
Shi, Ding
Wu, Wenrui
Wang, Shuting
Wang, Kaicen
Li, Yating
Yang, Liya
Bian, Xiaoyuan
Wang, Qiangqiang
Li, Lanjuan
Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title_full Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title_fullStr Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title_full_unstemmed Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title_short Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
title_sort intermittent fasting alleviates risk markers in a murine model of ulcerative colitis by modulating the gut microbiome and metabolome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788567/
https://www.ncbi.nlm.nih.gov/pubmed/36558471
http://dx.doi.org/10.3390/nu14245311
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