ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
This article is part of the Research TopicImpact of Diet on Gut Microbiome Regulation in Chronic Inflammation and Aging ProcessesView all 4 articles
Age-and Sex-Dependent Alterations of Jejunal Microbiota in Fischer 344 Rats Fed with a High-Fructose, High-Fat Diet: Depletion of Lactobacillus intestinalis in Small Bowel Contents
Provisionally accepted
- 1Department of Health Science and Technology, Seoul National University Graduate School of Convergence Science and Technology, Gwanak-gu, Republic of Korea
- 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
- 3Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
- 4Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Our previous research demonstrated high-fat diet (HFHFD) induced jejunal inflammation and hepatic steatosis, suggesting that small bowel microbiota contribute to these pathologies. This study investigated age-and sex-specific alterations in jejunal microbiota following HFHFD in F344 rats. Six-week-old and two-year-old rats of both sexes were fed a HFHFD for 8 weeks, after which jejunal contents were collected for metagenomic analysis. Taxonomic profiling and linear discriminant analysis revealed that HFHFD reduced the Firmicutes/Bacteroidetes ratio in young females and in aged rats of both sexes. Notably, Lactobacillus intestinalis—which supports barrier function—decreased in young males and aged females. In contrast, Akkermansia muciniphila increased across all HFHFD groups, particularly in young females and aged rats. Bacteroides vulgatus increased in aged HFHFD-fed rats of both sexes, while Bacteroides caccae was elevated in females across both age groups. Furthermore, the Lactobacillus reuteri group decreased only in young HFHFD rats. Spearman's rank correlation analysis revealed that L. intestinalis and L. reuteri groups negatively correlated with jejunal inflammation and hepatic steatosis. Conversely, B. caccae and A. muciniphila showed positive correlations with both pathogenic phenotypes. Beta-diversity revealed a pronounced diet-and sex-dependent separation in young rats, which was attenuated in aged groups. In HIEC-6 human intestinal epithelial cells, L. intestinalis significantly restored viability under palmitic acid–induced lipotoxic stress, though its the conditioned medium did not. Collectively, HFHFD induces age-and sex-dependent dysbiosis in the jejunum, and L. intestinalis may serve as a potential probiotic for metabolic dysfunction-associated steatotic liver disease.
Keywords: age, High-fructose high-fat diet, microbiota, Non-alcoholicfatty liver disease, Sex, Small bowel
Received: 01 Jan 2026; Accepted: 12 Feb 2026.
Copyright: © 2026 Ha, Kim and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nayoung Kim
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