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限时进食揭示了人类“更年轻”的免疫系统并重塑肠道微生物群。

Time-restricted eating reveals a "younger" immune system and reshapes the intestinal microbiome in human.

作者信息

Chen Yiran, Li Xi, Yang Ming, Jia Chen, He Zhenghao, Zhou Suqing, Ruan Pinglang, Wang Yikun, Tang Congli, Pan Wenjing, Long Hai, Zhao Ming, Lu Liwei, Peng Weijun, Akbar Arne, Wu Irene Xy, Li Song, Wu Haijing, Lu Qianjin

机构信息

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, 210042, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China; Research Unit of Key Technologies of Immune-related Skin Diseases Diagnosis and Treatment, Chinese Academy of Medical Sciences Institute of Dermatology, Nanjing, 210042, China.

Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China.

出版信息

Redox Biol. 2024 Dec;78:103422. doi: 10.1016/j.redox.2024.103422. Epub 2024 Nov 9.

DOI:10.1016/j.redox.2024.103422
PMID:39561680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11616606/
Abstract

Time-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities. However, the effect of TRE on the human immune system, especially on immunosenescence, intestinal microbiome, and metabolism remains unclear. We conducted a 30-day 16:8 TRE single-arm clinical trial with 49 participants. Participants consumed daily meals from 9 a.m. to 5 p.m., provided by a nutrition canteen with a balanced, calorie-appropriate nutrition, which is designed by clinical nutritionists (ChiCTR2200058137). We monitored weight changes and weight-related parameters and focused on changes in the frequency of CD4 senescent T cells, immune repertoire from peripheral blood, as well as serum metabolites and gut microbiota. We found that up to 95.9 % of subjects experienced sustained weight loss after TRE. The frequency of circulating senescent CD4 T cells was decreased, while the frequency of Th1, Treg, Tfh-like, and B cells was increased. Regarding the immune repertoire, the proportions of T cell receptor alpha and beta chains were increased, whereas B cell receptor kappa and lambda chains were reduced. In addition, a reduced class switch recombination from immunoglobulin M (IgM) to immunoglobulin A (IgA) was observed. TRE upregulated the levels of anti-inflammatory and anti-aging serum metabolites named sphingosine-1-phosphate and prostaglandin-1. Additionally, several anti-inflammatory bacteria and probiotics were increased, such as Akkermansia and Rikenellaceae, and the composition of the gut microbiota tended to be "younger". Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay "young". Clinical Trial Registration URL: https://www.chictr.org.cn/showproj.html?proj=159876.

摘要

限时进食(TRE)已被证明可通过影响代谢和抗炎活性来延长果蝇和小鼠模型的寿命。然而,TRE对人类免疫系统的影响,尤其是对免疫衰老、肠道微生物群和代谢的影响仍不清楚。我们进行了一项为期30天的16:8 TRE单臂临床试验,有49名参与者。参与者在上午9点至下午5点之间进食由营养食堂提供的每日餐食,该食堂由临床营养学家设计,提供均衡、热量适宜的营养(ChiCTR2200058137)。我们监测了体重变化和与体重相关的参数,并重点关注CD4衰老T细胞频率、外周血免疫库、血清代谢物和肠道微生物群的变化。我们发现,高达95.9%的受试者在TRE后体重持续减轻。循环衰老CD4 T细胞的频率降低,而Th1、Treg、Tfh样细胞和B细胞的频率增加。关于免疫库,T细胞受体α和β链的比例增加,而B细胞受体κ和λ链减少。此外,观察到从免疫球蛋白M(IgM)到免疫球蛋白A(IgA)的类别转换重组减少。TRE上调了名为鞘氨醇-1-磷酸和前列腺素-1的抗炎和抗衰老血清代谢物的水平。此外,几种抗炎细菌和益生菌增加,如阿克曼氏菌和理研菌科,肠道微生物群的组成趋于“年轻化”。总体而言,TRE显示出多种抗衰老作用,这可能有助于人类保持健康的生活方式以保持“年轻”。临床试验注册网址:https://www.chictr.org.cn/showproj.html?proj=159876 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/9b2931fff8f1/gr5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/e4a5ee6d7138/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/8f2a4a7fd7ba/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/9b2931fff8f1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/b6e110251370/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/95bc90bd5a5e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/4292da1d26db/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/e4a5ee6d7138/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4c6/11616606/8f2a4a7fd7ba/gr4.jpg
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