Journal of clinical and experimental hepatology · 2026
Integrated Analysis of Gut Microbiota and Bile Acid Metabolism Reveals a Distinct Pro-fibrotic Profile in Non-obese Patients With Nonalcoholic Fatty Liver Disease.
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Wang Shan, Li Zhixin, Wang Ya, Mai Meiqing, Ruan Rongdui, Guo Honghui
Аннотация
BACKGROUND/AIMS: This study aims to comprehensively analyze alterations in bile acid (BA) metabolism and gut microbiota composition to identify distinct metabolic signatures and microbial patterns associated with the development of nonalcoholic fatty liver disease (NAFLD) in non-obese individuals.
METHODS: This cross-sectional study enrolled 57 NAFLD patients, comprising 19 non-obese and 38 obese individuals. A multi-omics approach was employed, incorporating 16S rRNA sequencing to characterize gut microbiota and BA profiling to quantify serum and fecal BA concentrations. Statistical analyses included Spearman's correlation to assess associations between microorganisms and BAs, and Pearson's correlation to evaluate relationships between BAs and the Fibrosis-4 index.
RESULTS: Non-obese patients with NAFLD exhibit distinct gut microbiota profiles compared to their obese counterparts, characterized by an enrichment of Bacteroides (41.08% vs. 22.20%) and the Eubacterium_eligens_group (1.31% vs. 0.28%), as well as a significantly higher predicted potential for secondary BA synthesis. Bile acid profiling revealed distinct metabolic patterns: serum concentrations of glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), 7-keto-deoxycholic acid (7-keto-DCA), lithocholic acid (LCA), and 12-keto-lithocholic acid (12-keto-LCA) were significantly elevated in non-obese patients, with log2 fold change values ranging from 1.38 to 1.98. Notably, Bacteroides positively correlated with serum levels of DCA, 7-keto-DCA, and LCA. Furthermore, serum concentrations of GCDCA, 7-keto-DCA, and LCA demonstrated a positive correlation with the Fibrosis-4 index.
CONCLUSION: The findings reveal that non-obese NAFLD patients possess distinct BA and gut microbiota profiles, which may be associated with unique mechanisms contributing to liver fibrosis. These results underscore the need for tailored management strategies that differ from those used for obese NAFLD patients.
METHODS: This cross-sectional study enrolled 57 NAFLD patients, comprising 19 non-obese and 38 obese individuals. A multi-omics approach was employed, incorporating 16S rRNA sequencing to characterize gut microbiota and BA profiling to quantify serum and fecal BA concentrations. Statistical analyses included Spearman's correlation to assess associations between microorganisms and BAs, and Pearson's correlation to evaluate relationships between BAs and the Fibrosis-4 index.
RESULTS: Non-obese patients with NAFLD exhibit distinct gut microbiota profiles compared to their obese counterparts, characterized by an enrichment of Bacteroides (41.08% vs. 22.20%) and the Eubacterium_eligens_group (1.31% vs. 0.28%), as well as a significantly higher predicted potential for secondary BA synthesis. Bile acid profiling revealed distinct metabolic patterns: serum concentrations of glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), 7-keto-deoxycholic acid (7-keto-DCA), lithocholic acid (LCA), and 12-keto-lithocholic acid (12-keto-LCA) were significantly elevated in non-obese patients, with log2 fold change values ranging from 1.38 to 1.98. Notably, Bacteroides positively correlated with serum levels of DCA, 7-keto-DCA, and LCA. Furthermore, serum concentrations of GCDCA, 7-keto-DCA, and LCA demonstrated a positive correlation with the Fibrosis-4 index.
CONCLUSION: The findings reveal that non-obese NAFLD patients possess distinct BA and gut microbiota profiles, which may be associated with unique mechanisms contributing to liver fibrosis. These results underscore the need for tailored management strategies that differ from those used for obese NAFLD patients.