한빛사논문
- 조회773
Jeong Seok Yu1,**, Gi Soo Youn2,**, Jieun Choi1, Chang-Ho Kim1, Byung Yong Kim3, Seung-Jo Yang3, Je Hee Lee3, Tae-Sik Park4, Byoung Kook Kim5, Yeon Bee Kim1,6, Seong Woon Roh6, Byeong Hyun Min2, Hee Jin Park2, Sang Jun Yoon2, Na Young Lee2, Ye Rin Choi2, Hyeong Seob Kim2, Haripriya Gupta2, Hotaik Sung7, Sang Hak Han8, Ki Tae Suk2,**, Do Yup Lee1,**
1Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea
2Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
3ChunLab, Inc., Seoul, Republic of Korea
4Department of Life Science, Gachon University, Sungnam, Republic of Korea
5Chong Kun Dang Bio Research Institute, Gyeonggi-do, Republic of Korea
6Microbiology and Functionality Research Group, World Institute of Kimchi, Gwangju, Republic of Korea
7School of Medicine, Kyungpook National University, Daegu, Republic of Korea
8Department of Pathology, Hallym University College of Medicine, Chuncheon, Republic of Korea
Correspondence
Ki Tae Suk, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Gyo-dong,Chun-cheon 24252, Republic of Korea.
Do Yup Lee, Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
**These authors contributed equally to this study.
Abstract
Background
Although microbioa-based therapies have shown putative effects on the treatment of non-alcoholic fatty liver disease (NAFLD), it is not clear how microbiota-derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients.
Methods
We used Western diet-induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 109 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [n = 22] and NAFLD patients [n = 23]) were collected to investigate clinical reproducibility for microbiota-derived metabolites signature and metabolomics biomarker.
Results
L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut-tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti-inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes/Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD.
Conclusions
NAFLD progression was robustly associated with metabolic dys-regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut-liver axis.
논문정보
- Research article
- 2021년 12월 (BRIC 등록일 2022-01-10)
- 국내 연구진
- 생명과학 > 식품학
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