Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis
Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). St...
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2078612 |
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| author | Hyena Kang Hyun Ju You Giljae Lee Seung Hyun Lee Taekyeong Yoo Murim Choi Sae Kyung Joo Jeong Hwan Park Mee Soo Chang Dong Hyeon Lee Won Kim GwangPyo Ko |
| author_facet | Hyena Kang Hyun Ju You Giljae Lee Seung Hyun Lee Taekyeong Yoo Murim Choi Sae Kyung Joo Jeong Hwan Park Mee Soo Chang Dong Hyeon Lee Won Kim GwangPyo Ko |
| author_sort | Hyena Kang |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis. |
| format | Article |
| id | doaj-art-bbc8166ac87e4b0ab29bf5d383534de2 |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-bbc8166ac87e4b0ab29bf5d383534de22025-08-20T03:12:50ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2078612Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesisHyena Kang0Hyun Ju You1Giljae Lee2Seung Hyun Lee3Taekyeong Yoo4Murim Choi5Sae Kyung Joo6Jeong Hwan Park7Mee Soo Chang8Dong Hyeon Lee9Won Kim10GwangPyo Ko11Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Republic of KoreaDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Republic of KoreaDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Republic of KoreaDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of KoreaDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Republic of KoreaNonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis.https://www.tandfonline.com/doi/10.1080/19490976.2022.2078612Nonalcoholic fatty liver diseasegut microbiomehigh carbohydrate dietde novo lipogenesisliver transcriptome |
| spellingShingle | Hyena Kang Hyun Ju You Giljae Lee Seung Hyun Lee Taekyeong Yoo Murim Choi Sae Kyung Joo Jeong Hwan Park Mee Soo Chang Dong Hyeon Lee Won Kim GwangPyo Ko Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis Gut Microbes Nonalcoholic fatty liver disease gut microbiome high carbohydrate diet de novo lipogenesis liver transcriptome |
| title | Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| title_full | Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| title_fullStr | Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| title_full_unstemmed | Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| title_short | Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| title_sort | interaction effect between nafld severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis |
| topic | Nonalcoholic fatty liver disease gut microbiome high carbohydrate diet de novo lipogenesis liver transcriptome |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2078612 |
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