Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights

Aerobic exercise mitigates age-related intestinal senescence through gut microbiota modulation, but the underlying mechanism has remained unclear. In this study, we performed 16S rRNA sequencing of gut contents from young, old, and old exercise C57BL/6J mice to assess exercise-induced alterations in...

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Main Authors: Chunxia Yu, Xuanyu Liu, Yitong Li, Silin Li, Yating Huang, Sujuan Liu, Heng Shao, Yanna Shen, Li Fu
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/6/1379
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author Chunxia Yu
Xuanyu Liu
Yitong Li
Silin Li
Yating Huang
Sujuan Liu
Heng Shao
Yanna Shen
Li Fu
author_facet Chunxia Yu
Xuanyu Liu
Yitong Li
Silin Li
Yating Huang
Sujuan Liu
Heng Shao
Yanna Shen
Li Fu
author_sort Chunxia Yu
collection DOAJ
description Aerobic exercise mitigates age-related intestinal senescence through gut microbiota modulation, but the underlying mechanism has remained unclear. In this study, we performed 16S rRNA sequencing of gut contents from young, old, and old exercise C57BL/6J mice to assess exercise-induced alterations in microbiota community structure. Differential taxa analyses were applied to reveal age-associated bacterial signatures, gut barrier integrity, and systemic inflammation. Additionally, untargeted metabolomic profiling was employed to characterize gut metabolic profiles and reveal the key pathways through differential metabolite enrichment analyses. Aging significantly exacerbated the senescence-associated secretory phenotypes and the overgrowth of pathogenic bacteria in mice. However, aerobic exercise ameliorated these age-related deteriorations, restored gut microbial homeostasis, and reduced intestinal permeability. Notably, exercise intervention led to a significant increase in Akkermansia abundance in feces, establishing this mucin-degrading bacterium as a prominent exercise-responsive microbe. Metabolomic profiling identified eicosanoid metabolism as the most significantly perturbed pathway, and chronic exercise was found to regulate 14,15-Dhet levels. Our multi-omics integration confirmed that exercise is a potent modulator of the gut–microbiota–metabolite axis during aging. Elucidating the “Akkermansia–eicosanoid signaling” axis provided mechanistic insights into how exercise promotes healthy aging, identifying novel targets for anti-aging strategies via microbiota.
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spelling doaj-art-e69722545f0d44bc9f68207285acbe062025-08-20T03:27:25ZengMDPI AGMicroorganisms2076-26072025-06-01136137910.3390/microorganisms13061379Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics InsightsChunxia Yu0Xuanyu Liu1Yitong Li2Silin Li3Yating Huang4Sujuan Liu5Heng Shao6Yanna Shen7Li Fu8School of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaSchool of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaSchool of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaSchool of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaSchool of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaSchool of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaSchool of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaSchool of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaSchool of Medical Technology, Tianjin Medical University, Tianjin 300070, ChinaAerobic exercise mitigates age-related intestinal senescence through gut microbiota modulation, but the underlying mechanism has remained unclear. In this study, we performed 16S rRNA sequencing of gut contents from young, old, and old exercise C57BL/6J mice to assess exercise-induced alterations in microbiota community structure. Differential taxa analyses were applied to reveal age-associated bacterial signatures, gut barrier integrity, and systemic inflammation. Additionally, untargeted metabolomic profiling was employed to characterize gut metabolic profiles and reveal the key pathways through differential metabolite enrichment analyses. Aging significantly exacerbated the senescence-associated secretory phenotypes and the overgrowth of pathogenic bacteria in mice. However, aerobic exercise ameliorated these age-related deteriorations, restored gut microbial homeostasis, and reduced intestinal permeability. Notably, exercise intervention led to a significant increase in Akkermansia abundance in feces, establishing this mucin-degrading bacterium as a prominent exercise-responsive microbe. Metabolomic profiling identified eicosanoid metabolism as the most significantly perturbed pathway, and chronic exercise was found to regulate 14,15-Dhet levels. Our multi-omics integration confirmed that exercise is a potent modulator of the gut–microbiota–metabolite axis during aging. Elucidating the “Akkermansia–eicosanoid signaling” axis provided mechanistic insights into how exercise promotes healthy aging, identifying novel targets for anti-aging strategies via microbiota.https://www.mdpi.com/2076-2607/13/6/1379exerciseaginggut microbiotaeicosanoid metabolism
spellingShingle Chunxia Yu
Xuanyu Liu
Yitong Li
Silin Li
Yating Huang
Sujuan Liu
Heng Shao
Yanna Shen
Li Fu
Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
Microorganisms
exercise
aging
gut microbiota
eicosanoid metabolism
title Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
title_full Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
title_fullStr Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
title_full_unstemmed Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
title_short Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights
title_sort exercise remodels akkermansia associated eicosanoid metabolism to alleviate intestinal senescence multi omics insights
topic exercise
aging
gut microbiota
eicosanoid metabolism
url https://www.mdpi.com/2076-2607/13/6/1379
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