The sex-related differences in gut microbiota characteristics and keystone species identification of lipid metabolism in dyslipidemia
Abstract
BackgroundDyslipidemia exhibits pronounced sex-related differences, yet the integrated interactions among gut microbiota, host metabolism, and immune responses underlying these sex-related differences remain poorly understood.MethodsWe investigated sex-related alterations in gut microbiota composition, lipid metabolism, and inflammatory responses by integrating the re-analysis of a clinical cohort and mouse model in dyslipidemia, alongside isolation and identification of a keystone probiotic strain.ResultsHigh-fat diet (HFD) induced comparable hepatic steatosis and inflammation in both sexes. However, male mice exhibited earlier body weight gain and impaired intestinal barrier integrity (downregulated ZO-1/Occludin). Metabolomics analysis revealed distinct sex-related bile acid metabolic signatures, with females showing increased levels of several bile acids and enrichment of ascorbate and aldarate metabolism, while males exhibited reduced primary bile acids together with enrichment of bile acid biosynthesis and secretion pathways. Depletion of L. johnsonii observed in both clinical cohort and HFD mice was correlated with keystone taxa (Lactobacillus) and with lipid, inflammation, and bile acid markers. Moreover, the isolated L. johnsonii DM2420 strain exhibited cholesterol-lowering activity and BSH activity, harbored multiple genes associated with stress adaptation, and its supernatant metabolomics indicated bile acid remodeling in vitro.ConclusionCollectively, male mice exhibited greater susceptibility than females to HFD-induced dyslipidemia, which may be associated with the depletion of the candidate keystone taxon L. johnsonii in males and with related bile acid metabolic reprogramming. The isolated strain of L. johnsonii DM2420 exhibited a multifunctional profile that underscores its probiotic potential. Our findings preliminarily suggest a potential association between gut microbiota, bile acids, and immune responses in dyslipidemia and highlight the potential of keystone species-based precision strategies for sex-informed interventions.
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BibTeX
@article{xu2026sexrelated,
title = {{The sex-related differences in gut microbiota characteristics and keystone species identification of lipid metabolism in dyslipidemia}},
author = {Yafang Xu and Jinglong Jin and Jiaxin An and Qianrui Wei and Oumarou Chaibou Zafir and Zhijian Bo and Mingchun Luan and Liang Cao and Huajun Li},
journal = {Frontiers in Microbiology},
year = {2026},
month = nov,
doi = {10.3389/fmicb.2026.1970842},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1970842},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The sex-related differences in gut microbiota characteristics and keystone species identification of lipid metabolism in dyslipidemia
AU - Yafang Xu
AU - Jinglong Jin
AU - Jiaxin An
AU - Qianrui Wei
AU - Oumarou Chaibou Zafir
AU - Zhijian Bo
AU - Mingchun Luan
AU - Liang Cao
AU - Huajun Li
PY - 2026
DA - 2026/11/04
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1970842
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1970842
AB - BackgroundDyslipidemia exhibits pronounced sex-related differences, yet the integrated interactions among gut microbiota, host metabolism, and immune responses underlying these sex-related differences remain poorly understood.MethodsWe investigated sex-related alterations in gut microbiota composition, lipid metabolism, and inflammatory responses by integrating the re-analysis of a clinical cohort and mouse model in dyslipidemia, alongside isolation and identification of a keystone probiotic strain.ResultsHigh-fat diet (HFD) induced comparable hepatic steatosis and inflammation in both sexes. However, male mice exhibited earlier body weight gain and impaired intestinal barrier integrity (downregulated ZO-1/Occludin). Metabolomics analysis revealed distinct sex-related bile acid metabolic signatures, with females showing increased levels of several bile acids and enrichment of ascorbate and aldarate metabolism, while males exhibited reduced primary bile acids together with enrichment of bile acid biosynthesis and secretion pathways. Depletion of L. johnsonii observed in both clinical cohort and HFD mice was correlated with keystone taxa (Lactobacillus) and with lipid, inflammation, and bile acid markers. Moreover, the isolated L. johnsonii DM2420 strain exhibited cholesterol-lowering activity and BSH activity, harbored multiple genes associated with stress adaptation, and its supernatant metabolomics indicated bile acid remodeling in vitro.ConclusionCollectively, male mice exhibited greater susceptibility than females to HFD-induced dyslipidemia, which may be associated with the depletion of the candidate keystone taxon L. johnsonii in males and with related bile acid metabolic reprogramming. The isolated strain of L. johnsonii DM2420 exhibited a multifunctional profile that underscores its probiotic potential. Our findings preliminarily suggest a potential association between gut microbiota, bile acids, and immune responses in dyslipidemia and highlight the potential of keystone species-based precision strategies for sex-informed interventions.
SN - 1664-302X
ER -