Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet

Abstract Background Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies showed that IF is a promising approach for weight control, improving insulin sensitivity and reducing type 2 diabetes mellitus (T2DM) prevalence. Methods Twenty-eight 8-month-old...

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Main Authors: Ziru Li, Sufang Chen, Bingbing Yin, Jiacun Wei, Duofei Wang, Huoxiang Zhou, Zhi Sun
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Nutrition & Metabolism
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Online Access:https://doi.org/10.1186/s12986-025-00904-5
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author Ziru Li
Sufang Chen
Bingbing Yin
Jiacun Wei
Duofei Wang
Huoxiang Zhou
Zhi Sun
author_facet Ziru Li
Sufang Chen
Bingbing Yin
Jiacun Wei
Duofei Wang
Huoxiang Zhou
Zhi Sun
author_sort Ziru Li
collection DOAJ
description Abstract Background Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies showed that IF is a promising approach for weight control, improving insulin sensitivity and reducing type 2 diabetes mellitus (T2DM) prevalence. Methods Twenty-eight 8-month-old male C57BL/6J mice were randomly divided into a normal control group (NC), a high-fat diet group (HFD) and an HFD + IF group. Body weight (BW) and food intake were monitored weekly. After 20 weeks, the intraperitoneal glucose tolerance test (IPGTT), oral glucose tolerance test (OGTT), and intraperitoneal insulin tolerance test (IPITT) were performed weekly in sequence. Fresh faeces were collected to examine changes in gut microbiota, and serum untargeted metabolite profiling was conducted on serum samples. Results IF significantly reduced weight gain, fat mass and liver weight, improved glucose tolerance and insulin sensitivity in middle-aged mice fed with high-fat diet. 16 S rRNA gene sequencing revealed that IF significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio by increased Muribaculaceae, Bacteroides, Parabacteroides, and decreased Bilophila, Colidextribacter, Oscillibacter. The serum untargeted metabolomics revealed that IF could modulate differential metabolites and metabolic pathways associated with glycolipid metabolism. Spearman’s correlation analysis indicated that key differential microbiota were strongly correlated with glucose metabolism-related indicators and serum metabolites such as stearic acid, obeticholic acid, and N-acetylglycine. Conclusions IF improves glucose metabolism, regulates gut microbiota, and alters serum metabolites in middle-aged mice fed a high-fat diet. This provides a new pathway for trials testing diabetes prevention in middle-aged and elderly patients.
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spelling doaj-art-af6a5ceaf0344abb853228c8fc51cc9b2025-08-20T02:16:54ZengBMCNutrition & Metabolism1743-70752025-02-0122111410.1186/s12986-025-00904-5Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat dietZiru Li0Sufang Chen1Bingbing Yin2Jiacun Wei3Duofei Wang4Huoxiang Zhou5Zhi Sun6Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityLaboratory of Microbiology and Immunology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou UniversityDepartment of Pharmacy, Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies showed that IF is a promising approach for weight control, improving insulin sensitivity and reducing type 2 diabetes mellitus (T2DM) prevalence. Methods Twenty-eight 8-month-old male C57BL/6J mice were randomly divided into a normal control group (NC), a high-fat diet group (HFD) and an HFD + IF group. Body weight (BW) and food intake were monitored weekly. After 20 weeks, the intraperitoneal glucose tolerance test (IPGTT), oral glucose tolerance test (OGTT), and intraperitoneal insulin tolerance test (IPITT) were performed weekly in sequence. Fresh faeces were collected to examine changes in gut microbiota, and serum untargeted metabolite profiling was conducted on serum samples. Results IF significantly reduced weight gain, fat mass and liver weight, improved glucose tolerance and insulin sensitivity in middle-aged mice fed with high-fat diet. 16 S rRNA gene sequencing revealed that IF significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio by increased Muribaculaceae, Bacteroides, Parabacteroides, and decreased Bilophila, Colidextribacter, Oscillibacter. The serum untargeted metabolomics revealed that IF could modulate differential metabolites and metabolic pathways associated with glycolipid metabolism. Spearman’s correlation analysis indicated that key differential microbiota were strongly correlated with glucose metabolism-related indicators and serum metabolites such as stearic acid, obeticholic acid, and N-acetylglycine. Conclusions IF improves glucose metabolism, regulates gut microbiota, and alters serum metabolites in middle-aged mice fed a high-fat diet. This provides a new pathway for trials testing diabetes prevention in middle-aged and elderly patients.https://doi.org/10.1186/s12986-025-00904-5Intermittent fastingMiddle-aged miceGlucose metabolism disordersGut microbiotaSerum metabonomics
spellingShingle Ziru Li
Sufang Chen
Bingbing Yin
Jiacun Wei
Duofei Wang
Huoxiang Zhou
Zhi Sun
Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
Nutrition & Metabolism
Intermittent fasting
Middle-aged mice
Glucose metabolism disorders
Gut microbiota
Serum metabonomics
title Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
title_full Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
title_fullStr Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
title_full_unstemmed Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
title_short Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet
title_sort intermittent fasting regulates gut microbiota and serum metabolome profiles in middle aged mice fed high fat diet
topic Intermittent fasting
Middle-aged mice
Glucose metabolism disorders
Gut microbiota
Serum metabonomics
url https://doi.org/10.1186/s12986-025-00904-5
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