Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass

ABSTRACT Background This study aimed to explore the association between gut microbiota functional profiles and skeletal muscle mass, focusing on sex‐specific differences in a population under 65 years of age. Methods Stool samples from participants were analysed using metagenomic shotgun sequencing....

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Main Authors: Hang A. Park, Joohon Sung, Yoosoo Chang, Seungho Ryu, Kyung Jae Yoon, Hyung‐Lae Kim, Han‐Na Kim
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13636
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author Hang A. Park
Joohon Sung
Yoosoo Chang
Seungho Ryu
Kyung Jae Yoon
Hyung‐Lae Kim
Han‐Na Kim
author_facet Hang A. Park
Joohon Sung
Yoosoo Chang
Seungho Ryu
Kyung Jae Yoon
Hyung‐Lae Kim
Han‐Na Kim
author_sort Hang A. Park
collection DOAJ
description ABSTRACT Background This study aimed to explore the association between gut microbiota functional profiles and skeletal muscle mass, focusing on sex‐specific differences in a population under 65 years of age. Methods Stool samples from participants were analysed using metagenomic shotgun sequencing. Skeletal muscle mass and skeletal muscle mass index (SMI) were quantified (SMI [%] = total appendage muscle mass [kg]/body weight [kg] × 100) using bioelectrical impedance analysis. Participants were categorized into SMI quartiles, and associations between gut microbiota, functional profiling and SMI were assessed by sex, adjusting for age, BMI and physical activity. Results The cohort included 1027 participants (651 men, 376 women). In men, Escherichia coli (log2 fold change 3.08, q = 0.001), Ruminococcus_B gnavus (log2 fold change 2.89, q = 0.014) and Enterocloster sp001517625 (log2 fold change 2.47, q = 0.026) were more abundant in the lowest SMI compared to the highest SMI group. In contrast, Bifidobacterium bifidum (log2 fold change 3.13, q = 0.025) showed higher levels in the second lowest SMI group in women. Microbial pathways associated with amino acid synthesis (MET‐SAM‐PWY: log2 fold change 0.42; METSYN‐PWY: log2 fold change 0.44; SER‐GLYSYN‐PWY: log2 fold change 0.20; PWY‐5347: log2 fold change 0.41; P4‐PWY: log2 fold change 0.53), N‐acetylneuraminate degradation (log2 fold change 0.43), isoprene biosynthesis (log2 fold change 0.20) and purine nucleotide degradation and salvage (PWY‐6353: log2 fold change 0.42; PWY‐6608: log2 fold change 0.38; PWY66‐409: log2 fold change 0.52; SALVADEHYPOX‐PWY: log2 fold change 0.43) were enriched in the lowest SMI in men (q < 0.10). In women, the second lowest SMI group showed enrichment in energy‐related pathways, including lactic acid fermentation (ANAEROFRUCAT‐PWY: log2 fold change 0.19), pentose phosphate pathway (PENTOSE‐P‐PWY: log2 fold change 0.30) and carbohydrate degradation (PWY‐5484: log2 fold change 0.31; GLYCOLYSIS: log2 fold change 0.29; PWY‐6901: log2 fold change 0.27) (q < 0.05). Conclusions This study highlights sex‐specific differences in gut microbiota and functional pathways associated with SMI. These findings suggest that gut microbiota may play a role in muscle health and point toward microbiota‐targeted strategies for maintaining muscle mass.
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spelling doaj-art-630ab55dec794b908d446d6326f997da2025-08-20T02:06:27ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-02-01161n/an/a10.1002/jcsm.13636Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle MassHang A. Park0Joohon Sung1Yoosoo Chang2Seungho Ryu3Kyung Jae Yoon4Hyung‐Lae Kim5Han‐Na Kim6Genome and Health Big Data Laboratory, Graduate School of Public Health Seoul National University Seoul Republic of KoreaGenome and Health Big Data Laboratory, Graduate School of Public Health Seoul National University Seoul Republic of KoreaCenter for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Seoul Republic of KoreaCenter for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Seoul Republic of KoreaDepartment of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology Sungkyunkwan University Seoul Republic of KoreaDepartment of Biochemistry, College of Medicine Ewha Womans University Seoul Republic of KoreaDepartment of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology Sungkyunkwan University Seoul Republic of KoreaABSTRACT Background This study aimed to explore the association between gut microbiota functional profiles and skeletal muscle mass, focusing on sex‐specific differences in a population under 65 years of age. Methods Stool samples from participants were analysed using metagenomic shotgun sequencing. Skeletal muscle mass and skeletal muscle mass index (SMI) were quantified (SMI [%] = total appendage muscle mass [kg]/body weight [kg] × 100) using bioelectrical impedance analysis. Participants were categorized into SMI quartiles, and associations between gut microbiota, functional profiling and SMI were assessed by sex, adjusting for age, BMI and physical activity. Results The cohort included 1027 participants (651 men, 376 women). In men, Escherichia coli (log2 fold change 3.08, q = 0.001), Ruminococcus_B gnavus (log2 fold change 2.89, q = 0.014) and Enterocloster sp001517625 (log2 fold change 2.47, q = 0.026) were more abundant in the lowest SMI compared to the highest SMI group. In contrast, Bifidobacterium bifidum (log2 fold change 3.13, q = 0.025) showed higher levels in the second lowest SMI group in women. Microbial pathways associated with amino acid synthesis (MET‐SAM‐PWY: log2 fold change 0.42; METSYN‐PWY: log2 fold change 0.44; SER‐GLYSYN‐PWY: log2 fold change 0.20; PWY‐5347: log2 fold change 0.41; P4‐PWY: log2 fold change 0.53), N‐acetylneuraminate degradation (log2 fold change 0.43), isoprene biosynthesis (log2 fold change 0.20) and purine nucleotide degradation and salvage (PWY‐6353: log2 fold change 0.42; PWY‐6608: log2 fold change 0.38; PWY66‐409: log2 fold change 0.52; SALVADEHYPOX‐PWY: log2 fold change 0.43) were enriched in the lowest SMI in men (q < 0.10). In women, the second lowest SMI group showed enrichment in energy‐related pathways, including lactic acid fermentation (ANAEROFRUCAT‐PWY: log2 fold change 0.19), pentose phosphate pathway (PENTOSE‐P‐PWY: log2 fold change 0.30) and carbohydrate degradation (PWY‐5484: log2 fold change 0.31; GLYCOLYSIS: log2 fold change 0.29; PWY‐6901: log2 fold change 0.27) (q < 0.05). Conclusions This study highlights sex‐specific differences in gut microbiota and functional pathways associated with SMI. These findings suggest that gut microbiota may play a role in muscle health and point toward microbiota‐targeted strategies for maintaining muscle mass.https://doi.org/10.1002/jcsm.13636gut microbiomemetagenomicsmicrobial functionsarcopeniaskeletal muscle mass
spellingShingle Hang A. Park
Joohon Sung
Yoosoo Chang
Seungho Ryu
Kyung Jae Yoon
Hyung‐Lae Kim
Han‐Na Kim
Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
Journal of Cachexia, Sarcopenia and Muscle
gut microbiome
metagenomics
microbial function
sarcopenia
skeletal muscle mass
title Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
title_full Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
title_fullStr Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
title_full_unstemmed Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
title_short Metagenomic Analysis Identifies Sex‐Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass
title_sort metagenomic analysis identifies sex related gut microbial functions and bacterial taxa associated with skeletal muscle mass
topic gut microbiome
metagenomics
microbial function
sarcopenia
skeletal muscle mass
url https://doi.org/10.1002/jcsm.13636
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