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Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice

Regular environmental light–dark (LD) cycle-regulated period circadian clock 2 (Per2) gene expression is essential for circadian oscillation, nutrient metabolism, and intestinal microbiota balance. Herein, we combined environmental LD cycles with Per2 gene knockout to investigate how LD cycles media...

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Autores principales: Zhen, Yongkang, Ge, Ling, Xu, Qiaoyun, Hu, Liangyu, Wei, Wenjun, Huang, Jiantao, Loor, Juan J., Yang, Qingyong, Wang, Mengzhi, Zhou, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971677/
https://www.ncbi.nlm.nih.gov/pubmed/35371053
http://dx.doi.org/10.3389/fimmu.2022.848248
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author Zhen, Yongkang
Ge, Ling
Xu, Qiaoyun
Hu, Liangyu
Wei, Wenjun
Huang, Jiantao
Loor, Juan J.
Yang, Qingyong
Wang, Mengzhi
Zhou, Ping
author_facet Zhen, Yongkang
Ge, Ling
Xu, Qiaoyun
Hu, Liangyu
Wei, Wenjun
Huang, Jiantao
Loor, Juan J.
Yang, Qingyong
Wang, Mengzhi
Zhou, Ping
author_sort Zhen, Yongkang
collection PubMed
description Regular environmental light–dark (LD) cycle-regulated period circadian clock 2 (Per2) gene expression is essential for circadian oscillation, nutrient metabolism, and intestinal microbiota balance. Herein, we combined environmental LD cycles with Per2 gene knockout to investigate how LD cycles mediate Per2 expression to regulate colonic and cecal inflammatory and barrier functions, microbiome, and short-chain fatty acids (SCFAs) in the circulation. Mice were divided into knockout (KO) and wild type (CON) under normal light–dark cycle (NLD) and short-light (SL) cycle for 2 weeks after 4 weeks of adaptation. The concentrations of SCFAs in the serum and large intestine, the colonic and cecal epithelial circadian rhythm, SCFAs transporter, inflammatory and barrier-related genes, and Illumina 16S rRNA sequencing were measured after euthanasia during 10:00–12:00. KO decreased the feeding frequency at 0:00–2:00 but increased at 12:00–14:00 both under NLD and SL. KO upregulated the expression of Per1 and Rev-erbα in the colon and cecum, while it downregulated Clock and Bmal1. In terms of inflammatory and barrier functions, KO increased the expression of Tnf-α, Tlr2, and Nf-κb p65 in the colon and cecum, while it decreased Claudin and Occludin-1. KO decreased the concentrations of total SCFAs and acetate in the colon and cecum, but it increased butyrate, while it had no impact on SCFAs in the serum. KO increased the SCFAs transporter because of the upregulation of Nhe1, Nhe3, and Mct4. Sequencing data revealed that KO improved bacteria α-diversity and increased Lachnospiraceae and Ruminococcaceae abundance, while it downregulated Erysipelatoclostridium, Prevotellaceae UCG_001, Olsenella, and Christensenellaceae R-7 under NLD in KO mice. Most of the differential bacterial genus were enriched in amino acid and carbohydrate metabolism pathways. Overall, Per2 knockout altered circadian oscillation in the large intestine, KO improved intestinal microbiota diversity, the increase in Clostridiales abundance led to the reduction in SCFAs in the circulation, concentrations of total SCFAs and acetate decreased, while butyrate increased and SCFAs transport was enhanced. These alterations may potentially lead to inflammation of the large intestine. Short-light treatment had minor impact on intestinal microbiome and metabolism.
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spelling pubmed-89716772022-04-02 Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice Zhen, Yongkang Ge, Ling Xu, Qiaoyun Hu, Liangyu Wei, Wenjun Huang, Jiantao Loor, Juan J. Yang, Qingyong Wang, Mengzhi Zhou, Ping Front Immunol Immunology Regular environmental light–dark (LD) cycle-regulated period circadian clock 2 (Per2) gene expression is essential for circadian oscillation, nutrient metabolism, and intestinal microbiota balance. Herein, we combined environmental LD cycles with Per2 gene knockout to investigate how LD cycles mediate Per2 expression to regulate colonic and cecal inflammatory and barrier functions, microbiome, and short-chain fatty acids (SCFAs) in the circulation. Mice were divided into knockout (KO) and wild type (CON) under normal light–dark cycle (NLD) and short-light (SL) cycle for 2 weeks after 4 weeks of adaptation. The concentrations of SCFAs in the serum and large intestine, the colonic and cecal epithelial circadian rhythm, SCFAs transporter, inflammatory and barrier-related genes, and Illumina 16S rRNA sequencing were measured after euthanasia during 10:00–12:00. KO decreased the feeding frequency at 0:00–2:00 but increased at 12:00–14:00 both under NLD and SL. KO upregulated the expression of Per1 and Rev-erbα in the colon and cecum, while it downregulated Clock and Bmal1. In terms of inflammatory and barrier functions, KO increased the expression of Tnf-α, Tlr2, and Nf-κb p65 in the colon and cecum, while it decreased Claudin and Occludin-1. KO decreased the concentrations of total SCFAs and acetate in the colon and cecum, but it increased butyrate, while it had no impact on SCFAs in the serum. KO increased the SCFAs transporter because of the upregulation of Nhe1, Nhe3, and Mct4. Sequencing data revealed that KO improved bacteria α-diversity and increased Lachnospiraceae and Ruminococcaceae abundance, while it downregulated Erysipelatoclostridium, Prevotellaceae UCG_001, Olsenella, and Christensenellaceae R-7 under NLD in KO mice. Most of the differential bacterial genus were enriched in amino acid and carbohydrate metabolism pathways. Overall, Per2 knockout altered circadian oscillation in the large intestine, KO improved intestinal microbiota diversity, the increase in Clostridiales abundance led to the reduction in SCFAs in the circulation, concentrations of total SCFAs and acetate decreased, while butyrate increased and SCFAs transport was enhanced. These alterations may potentially lead to inflammation of the large intestine. Short-light treatment had minor impact on intestinal microbiome and metabolism. Frontiers Media S.A. 2022-03-18 /pmc/articles/PMC8971677/ /pubmed/35371053 http://dx.doi.org/10.3389/fimmu.2022.848248 Text en Copyright © 2022 Zhen, Ge, Xu, Hu, Wei, Huang, Loor, Yang, Wang and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhen, Yongkang
Ge, Ling
Xu, Qiaoyun
Hu, Liangyu
Wei, Wenjun
Huang, Jiantao
Loor, Juan J.
Yang, Qingyong
Wang, Mengzhi
Zhou, Ping
Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title_full Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title_fullStr Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title_full_unstemmed Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title_short Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice
title_sort normal light-dark and short-light cycles regulate intestinal inflammation, circulating short-chain fatty acids and gut microbiota in period2 gene knockout mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971677/
https://www.ncbi.nlm.nih.gov/pubmed/35371053
http://dx.doi.org/10.3389/fimmu.2022.848248
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