New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model
ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index;...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-03-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01027-23 |
| _version_ | 1797257216799014912 |
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| author | Wenji Zhang Wenli Cheng JingHui Li Zhenrui Huang Hui Lin Wenjuan Zhang |
| author_facet | Wenji Zhang Wenli Cheng JingHui Li Zhenrui Huang Hui Lin Wenjuan Zhang |
| author_sort | Wenji Zhang |
| collection | DOAJ |
| description | ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD.IMPORTANCEPatients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, together with the predominant flora including g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium, were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant. |
| first_indexed | 2024-04-24T22:34:07Z |
| format | Article |
| id | doaj.art-d710a1db312f4564a84f8cf7ad9ecfd8 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-04-24T22:34:07Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-d710a1db312f4564a84f8cf7ad9ecfd82024-03-19T13:01:37ZengAmerican Society for MicrobiologymSystems2379-50772024-03-019310.1128/msystems.01027-23New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse modelWenji Zhang0Wenli Cheng1JingHui Li2Zhenrui Huang3Hui Lin4Wenjuan Zhang5Guangdong Provincial Engineering and Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaNingbo Psychiatric Hospital, Ningbo, ChinaGuangdong Provincial Engineering and Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaDepartment of Radiation Oncology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD.IMPORTANCEPatients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, together with the predominant flora including g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium, were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.https://journals.asm.org/doi/10.1128/msystems.01027-23non-obese non-alcoholic fatty liver diseaseintestinal florafecal metabolomics |
| spellingShingle | Wenji Zhang Wenli Cheng JingHui Li Zhenrui Huang Hui Lin Wenjuan Zhang New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model mSystems non-obese non-alcoholic fatty liver disease intestinal flora fecal metabolomics |
| title | New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model |
| title_full | New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model |
| title_fullStr | New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model |
| title_full_unstemmed | New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model |
| title_short | New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model |
| title_sort | new aspects characterizing non obese nafld by the analysis of the intestinal flora and metabolites using a mouse model |
| topic | non-obese non-alcoholic fatty liver disease intestinal flora fecal metabolomics |
| url | https://journals.asm.org/doi/10.1128/msystems.01027-23 |
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