Multi-omics analyses of the gut microbiota and metabolites in children with metabolic dysfunction-associated steatotic liver disease
This study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and t...
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| Published in | mSystems Vol. 10; no. 4; p. e0114824 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Microbiology
22.04.2025
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2379-5077 2379-5077 |
| DOI | 10.1128/msystems.01148-24 |
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| Abstract | This study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. |
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| AbstractList | ABSTRACTThe development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6–16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6-16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified and as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography ( ) values (≥6.2 kPa) showed an increased abundance of , which was positively correlated with the levels of deoxycholic acid (DCA) and values. Importantly, the mediation analysis identified positive associations between and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that may serve as a novel clinical target in pediatric MASLD. ABSTRACT The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6–16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6–16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6-16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD.The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6-16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6–16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography ( E ) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques , which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management. This study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD. |
| Author | Du, Landuoduo Zhang, Huiwen Lu, Deyun Zhou, Yongchang Fan, Jiangao Wang, Ying Zhang, Kaichuang Liang, Lili Ren, Tianyi Jiang, Lu Yang, Yi |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40084870$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2025 Du et al. Copyright © 2025 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2025 Du et al. 2025 Du et al. |
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| Keywords | deoxycholic acid biomarker steatosis Ruminococcus torques pediatric |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Landuoduo Du and Kaichuang Zhang contributed equally to this article. Author order was determined based on the extent of their individual contributions to the different sections of the research and the manuscript preparation. The authors declare no conflict of interest. |
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| Snippet | This study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver... The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut... ABSTRACTThe development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut... ABSTRACT The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut... |
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| SubjectTerms | Adolescent Alanine transaminase biomarker Biomarkers - metabolism Body mass index Case-Control Studies Child Children Children & youth Clinical Microbiology Deoxycholic acid DNA sequencing Fatty Liver - metabolism Fatty Liver - microbiology Feces Feces - microbiology Female Gastrointestinal Microbiome Gut microbiota Homogenization Humans Intestinal microflora Liver diseases Male Metabolism Metabolites Metabolomics Metabolomics - methods Microbiota Multiomics Non-alcoholic Fatty Liver Disease - metabolism Non-alcoholic Fatty Liver Disease - microbiology Obesity Patients pediatric Pediatrics Research Article Ribosomal DNA Ruminococcus Ruminococcus torques Software steatosis Taxonomy Variance analysis |
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| Title | Multi-omics analyses of the gut microbiota and metabolites in children with metabolic dysfunction-associated steatotic liver disease |
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