Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism
Abstract
:1. Introduction
2. Results
2.1. POST Ameliorated the Obesity-Related Parameters
2.2. POST-Attenuated IR and Improved Serum Lipid Parameters
2.3. POST Prevented Hepatic Steatosis and Dysfunction
2.4. POST Attenuated HFD-Induced Hepatic Inflammation
2.5. POST Altered the Gut Microbiota Composition
2.6. Correlation Analysis and Prediction of Microbial Metabolic Function
2.7. POST Modulated the Hepatic Metabolome in HFD Mice
2.8. POST Regulated Hepatic Lipid Metabolism Gene Expression
3. Discussion
4. Materials and Methods
4.1. Postbiotics Preparation
4.2. Animal Experiments
4.3. Oral Glucose Tolerance Test (OGTT)
4.4. Serum Biochemical Index Assays
4.5. Histological Analysis
4.6. Liver Inflammatory Cytokine Assay
4.7. Gut Microbiota Sequencing
4.8. Liver Metabolomics
4.9. Quantitative Reverse Transcription PCR (qRT-PCR)
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Friedman, S.L.; Neuschwander-Tetri, B.A.; Rinella, M.; Sanyal, A.J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 2018, 24, 908–922. [Google Scholar] [CrossRef] [PubMed]
- Anstee, Q.M.; Targher, G.; Day, C.P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 330–344. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Du, H.; Shen, M.; Zhao, Z.; Ye, X. Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway. J. Immunol. Res. 2020, 2020, e3413186. [Google Scholar] [CrossRef] [PubMed]
- Younossi, Z.M.; Loomba, R.; Rinella, M.E.; Bugianesi, E.; Marchesini, G.; Neuschwander-Tetri, B.A.; Serfaty, L.; Negro, F.; Caldwell, S.H.; Ratziu, V.; et al. Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 2018, 68, 361–371. [Google Scholar] [CrossRef] [Green Version]
- Salminen, S.; Collado, M.C.; Endo, A.; Hill, C.; Lebeer, S.; Quigley, E.M.M.; Sanders, M.E.; Shamir, R.; Swann, J.R.; Szajewska, H.; et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 649–667. [Google Scholar] [CrossRef]
- Moradi, M.; Mardani, K.; Tajik, H. Characterization and application of postbiotics of Lactobacillus spp. on Listeria monocytogenes in vitro and in food models. LWT-Food Sci. Technol. 2019, 111, 457–464. [Google Scholar] [CrossRef]
- Wegh, C.A.M.; Geerlings, S.Y.; Knol, J.; Roeselers, G.; Belzer, C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int. J. Mol. Sci. 2019, 20, 4673. [Google Scholar] [CrossRef] [Green Version]
- Kikuchi, K.; Ben Othman, M.; Sakamoto, K. Sterilized bifidobacteria suppressed fat accumulation and blood glucose level. Biochem. Biophys. Res. Commun. 2018, 501, 1041–1047. [Google Scholar] [CrossRef]
- Jensen, B.A.H.; Holm, J.B.; Larsen, I.S.; von Burg, N.; Derer, S.; Sonne, S.B.; Pærregaard, S.I.; Damgaard, M.V.; Indrelid, S.A.; Rivollier, A.; et al. Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism. Nat. Commun. 2021, 12, 1093. [Google Scholar] [CrossRef]
- Jayakumar, S.; Loomba, R. Review article: Emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications. Aliment. Pharmacol. Ther. 2019, 50, 144–158. [Google Scholar] [CrossRef]
- Porras, D.; Nistal, E.; Martínez-Flórez, S.; Olcoz, J.L.; Jover, R.; Jorquera, F.; González-Gallego, J.; García-Mediavilla, M.V.; Sánchez-Campos, S. Functional Interactions between Gut Microbiota Transplantation, Quercetin, and High-Fat Diet Determine Non-Alcoholic Fatty Liver Disease Development in Germ-Free Mice. Mol. Nutr. Food Res. 2019, 63, e1800930. [Google Scholar] [CrossRef] [PubMed]
- Vajro, P.; Paolella, G.; Fasano, A. Microbiota and Gut–Liver Axis: Their Influences on Obesity and Obesity-Related Liver Disease. J. Pediatr. Gastroenterol. Nutr. 2013, 56, 461–468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, Y.Y.; Li, L.; Yu, C.H.; Shen, Z.; Chen, L.H.; Li, Y.M. Effects of probiotics on nonalcoholic fatty liver disease: A meta-analysis. World J. Gastroenterol. 2013, 19, 6911–6918. [Google Scholar] [CrossRef] [PubMed]
- Su, G.; Wang, H.; Bai, J.; Chen, G.; Pei, Y. A Metabonomics Approach to Drug Toxicology in Liver Disease and its Application in Traditional Chinese Medicine. Curr. Drug Metab. 2019, 20, 292–300. [Google Scholar] [CrossRef]
- Zhang, A.; Sun, H.; Yan, G.; Wang, P.; Wang, X. Mass spectrometry-based metabolomics: Applications to biomarker and metabolic pathway research. Biomed. Chromatogr. 2016, 30, 7–12. [Google Scholar] [CrossRef]
- Yu, M.; Zhu, Y.; Cong, Q.; Wu, C. Metabonomics Research Progress on Liver Diseases. Can. J. Gastroenterol. Hepatol. 2017, 2017, e8467192. [Google Scholar] [CrossRef] [Green Version]
- Cui, H.; Li, Y.; Cao, M.; Liao, J.; Liu, X.; Miao, J.; Fu, H.; Song, R.; Wen, W.; Zhang, Z.; et al. Untargeted Metabolomic Analysis of the Effects and Mechanism of Nuciferine Treatment on Rats With Nonalcoholic Fatty Liver Disease. Front. Pharmacol. 2020, 11, 1663–9812. [Google Scholar] [CrossRef]
- Lv, X.-C.; Chen, M.; Huang, Z.-R.; Guo, W.-L.; Ai, L.-Z.; Bai, W.-D.; Yu, X.-D.; Liu, Y.-L.; Rao, P.-F.; Ni, L. Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet. Food Res. Int. 2021, 139, 109956. [Google Scholar] [CrossRef]
- Fabbrini, E.; Sullivan, S.; Klein, S. Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology 2010, 51, 679–689. [Google Scholar] [CrossRef] [Green Version]
- Iacono, A.; Raso, G.M.; Canani, R.B.; Calignano, A.; Meli, R. Probiotics as an emerging therapeutic strategy to treat NAFLD: Focus on molecular and biochemical mechanisms. J. Nutr. Biochem. 2011, 22, 699–711. [Google Scholar] [CrossRef]
- Sharpton, S.; Schnabl, B.; Knight, R.; Loomba, R. Current Concepts, Opportunities, and Challenges of Gut Microbiome-Based Personalized Medicine in Nonalcoholic Fatty Liver Disease. Cell Metab. 2020, 33, 21–32. [Google Scholar] [CrossRef]
- Lee, J.; Park, S.; Oh, N.; Park, J.; Kwon, M.; Seo, J.; Roh, S. Oral intake of Lactobacillus plantarum L-14 extract alleviates TLR2- and AMPK-mediated obesity-associated disorders in high-fat-diet-induced obese C57BL/6J mice. Cell Prolif. 2021, 54, e13039. [Google Scholar] [CrossRef]
- Ashrafian, F.; Raftar, S.K.A.; Lari, A.; Shahryari, A.; Abdollahiyan, S.; Moradi, H.R.; Masoumi, M.; Davari, M.; Khatami, S.; Omrani, M.D.; et al. Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice. Microb. Cell Factories 2021, 20, 219. [Google Scholar] [CrossRef] [PubMed]
- Aydos, L.R.; Amaral, L.A.D.; de Souza, R.S.; Jacobowski, A.C.; dos Santos, E.F.; Macedo, M.L.R. Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in C57bl/6 Models. Nutrients 2019, 11, 3067. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, G.; Xie, M.; Wan, P.; Chen, D.; Dai, Z.; Ye, H.; Hu, B.; Zeng, X.; Liu, Z. Fuzhuan Brick Tea Polysaccharides Attenuate Metabolic Syndrome in High-Fat Diet Induced Mice in Association with Modulation in the Gut Microbiota. J. Agric. Food Chem. 2018, 66, 2783–2795. [Google Scholar] [CrossRef] [PubMed]
- Ioannou, G.N. Implications of Elevated Serum Alanine Aminotransferase Levels: Think Outside the Liver. Gastroenterology 2008, 135, 1851–1854. [Google Scholar] [CrossRef]
- Sakurai, Y.; Kubota, N.; Yamauchi, T.; Kadowaki, T. Role of Insulin Resistance in MAFLD. Int. J. Mol. Sci. 2021, 22, 4156. [Google Scholar] [CrossRef]
- Fuchs, C.D.; Claudel, T.; Trauner, M. Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD. Trends Endocrinol. Metab. 2014, 25, 576–585. [Google Scholar] [CrossRef]
- Ding, Y.; Sun, X.; Chen, Y.; Deng, Y.; Qian, K. Epigallocatechin gallate attenuated non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. Eur. J. Pharmacol. 2015, 761, 405–412. [Google Scholar] [CrossRef]
- Leung, C.; Rivera, L.; Furness, J.B.; Angus, C.L.P.W. The role of the gut microbiota in NAFLD. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 412–425. [Google Scholar] [CrossRef]
- Ley, R.E.; Bäckhed, F.; Turnbaugh, P.; Lozupone, C.A.; Knight, R.D.; Gordon, J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005, 102, 11070–11075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kameyama, K.; Itoh, K. Intestinal Colonization by a Lachnospiraceae Bacterium Contributes to the Development of Diabetes in Obese Mice. Microbes Environ. 2014, 29, 427–430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, A.; Wang, N.; Li, N.; Li, B.; Yan, F.; Song, Y.; Hou, J.; Huo, G. Modulation effect of chenpi extract on gut microbiota in high-fat diet-induced obese C57BL/6 mice. J. Food Biochem. 2021, 45, e13541. [Google Scholar] [CrossRef] [PubMed]
- Stanislawski, M.A.; Lozupone, C.A.; Wagner, B.D.; Eggesbø, M.; Sontag, M.K.; Nusbacher, N.M.; Martinez, M.; Dabelea, D. Gut microbiota in adolescents and the association with fatty liver: The EPOCH study. Pediatr. Res. 2018, 84, 219–227. [Google Scholar] [CrossRef]
- Milton-Laskibar, I.; Cuevas-Sierra, A.; Portillo, M.P.; Martínez, J.A. Effects of Resveratrol Administration in Liver Injury Prevention as Induced by an Obesogenic Diet: Role of Ruminococcaceae. Biomedicines 2022, 10, 1797. [Google Scholar] [CrossRef]
- Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M.; et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 2013, 110, 9066–9071. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Wang, Y.; Wu, F.; Wang, X.; Feng, Y.; Wang, Y. MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila. Int. J. Biol. Macromol. 2022, 196, 23–34. [Google Scholar] [CrossRef] [PubMed]
- Kirpich, A.S.; Ibarra, M.; Moskalenko, O.; Fear, J.; Gerken, J.; Mi, X.; Ashrafi, A.; Morse, A.M.; McIntyre, L.M. SECIMTools: A suite of metabolomics data analysis tools. BMC Bioinform. 2018, 19, 2131–2134. [Google Scholar] [CrossRef]
- Mesens, N.; Desmidt, M.; Verheyen, G.R.; Starckx, S.; Damsch, S.; De Vries, R.; Verhemeldonck, M.; Van Gompel, J.; Lampo, A.; Lammens, L. Phospholipidosis in Rats Treated with Amiodarone: Serum Biochemistry and Whole Genome Micro-Array Analysis Supporting the Lipid Traffic Jam Hypothesis and the Subsequent Rise of the Biomarker BMP. Toxicol. Pathol. 2012, 40, 491–503. [Google Scholar] [CrossRef]
- van der Veen, J.N.; Kennelly, J.P.; Wan, S.; Vance, J.E.; Vance, D.E.; Jacobs, R.L. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim. Biophys. Acta (BBA)-Biomembr. 2017, 1859, 1558–1572. [Google Scholar] [CrossRef]
- Eisinger, K.; Krautbauer, S.; Hebel, T.; Schmitz, G.; Aslanidis, C.; Liebisch, G.; Buechler, C. Lipidomic analysis of the liver from high-fat diet induced obese mice identifies changes in multiple lipid classes. Exp. Mol. Pathol. 2014, 97, 37–43. [Google Scholar] [CrossRef] [PubMed]
- Lodhi, I.J.; Wei, X.; Yin, L.; Feng, C.; Adak, S.; Abou-Ezzi, G.; Hsu, F.-F.; Link, D.C.; Semenkovich, C.F. Peroxisomal Lipid Synthesis Regulates Inflammation by Sustaining Neutrophil Membrane Phospholipid Composition and Viability. Cell Metab. 2015, 21, 51–64. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jang, J.E.; Park, H.-S.; Yoo, H.J.; Baek, I.-J.; Yoon, J.E.; Ko, M.S.; Kim, A.-R.; Kim, H.S.; Park, H.-S.; Lee, S.E.; et al. Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice. Hepatology 2017, 66, 416–431. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, W.; Zhang, B.; Jiang, R. Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass. Biotechnol. Biofuels 2017, 10, 1–9. [Google Scholar] [CrossRef] [Green Version]
- Depeint, F.; Bruce, W.R.; Shangari, N.; Mehta, R.; O’Brien, P.J. Mitochondrial function and toxicity: Role of B vitamins on the one-carbon transfer pathways. Chem.-Biol. Interact. 2006, 163, 113–132. [Google Scholar] [CrossRef]
- Fiore, A.; Murray, P.J. Tryptophan and indole metabolism in immune regulation. Curr. Opin. Immunol. 2021, 70, 7–14. [Google Scholar] [CrossRef]
- Kim, Y.; Choi, S.; Lee, S.; Park, S.; Kim, J.Y.; Park, T.; Kwon, O. Characterization and Validation of an “Acute Aerobic Exercise Load” as a Tool to Assess Antioxidative and Anti-inflammatory Nutrition in Healthy Subjects Using a Statistically Integrated Approach in a Comprehensive Clinical Trial. Oxidative Med. Cell. Longev. 2019, 2019, e952672. [Google Scholar] [CrossRef]
- Yu, D.; Shu, X.-O.; Xiang, Y.-B.; Li, H.; Yang, G.; Gao, Y.-T.; Zheng, W.; Zhang, X. Higher Dietary Choline Intake Is Associated with Lower Risk of Nonalcoholic Fatty Liver in Normal-Weight Chinese Women. J. Nutr. 2014, 144, 2034–2040. [Google Scholar] [CrossRef] [Green Version]
- Lee, S.; Han, K.-H.; Nakamura, Y.; Kawakami, S.; Shimada, K.-I.; Hayakawa, T.; Onoue, H.; Fukushima, M. Dietary L-Cysteine Improves the Antioxidative Potential and Lipid Metabolism in Rats Fed a Normal Diet. Biosci. Biotechnol. Biochem. 2013, 77, 1430–1434. [Google Scholar] [CrossRef] [Green Version]
- Xie, Z.; Li, H.; Wang, K.; Lin, J.; Wang, Q.; Zhao, G.; Jia, W.; Zhang, Q. Analysis of transcriptome and metabolome profiles alterations in fatty liver induced by high-fat diet in rat. Metab.-Clin. Exp. 2010, 59, 554–560. [Google Scholar] [CrossRef]
- Reddy, J.K.; Rao, M.S. Lipid Metabolism and Liver Inflammation. II. Fatty liver disease and fatty acid oxidation. Am. J. Physiol.-Gastroint. Liver Physiol. 2006, 290, G852–G858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pettinelli, P.; Videla, L.A. Up-Regulation of PPAR-γ mRNA Expression in the Liver of Obese Patients: An Additional Reinforcing Lipogenic Mechanism to SREBP-1c Induction. J. Clin. Endocrinol. Metab. 2011, 96, 1424–1430. [Google Scholar] [CrossRef] [PubMed]
- Porras, D.; Nistal, E.; Martínez-Flórez, S.; González-Gallego, J.; García-Mediavilla, M.V.; Sánchez-Campos, S. Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease. Front. Physiol. 2018, 9, e01813. [Google Scholar] [CrossRef] [PubMed]
- Rada, P.; González-Rodríguez, Á.; García-Monzón, C.; Valverde, Á.M. Understanding lipotoxicity in NAFLD pathogenesis: Is CD36 a key driver? Cell Death Dis. 2020, 11, 802. [Google Scholar] [CrossRef]
- Enooku, K.; Tsutsumi, T.; Kondo, M.; Fujiwara, N.; Sasako, T.; Shibahara, J.; Kado, A.; Okushin, K.; Fujinaga, H.; Nakagomi, R.; et al. Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients. J. Gastroenterol. 2020, 55, 227–243. [Google Scholar] [CrossRef]
- Chakrabarti, P.; Kandror, K.V. FoxO1 Controls Insulin-dependent Adipose Triglyceride Lipase (ATGL) Expression and Lipolysis in Adipocytes. J. Biol. Chem. 2009, 284, 13296–13300. [Google Scholar] [CrossRef] [Green Version]
- Zechner, R.; Kienesberger, P.C.; Haemmerle, G.; Zimmermann, R.; Lass, A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J. Lipid Res. 2009, 50, 3–21. [Google Scholar] [CrossRef] [Green Version]
- Reid, B.N.; Ables, G.P.; Otlivanchik, O.A.; Schoiswohl, G.; Zechner, R.; Blaner, W.S.; Goldberg, I.J.; Schwabe, R.F.; Chua, S.C.; Huang, L.-S. Hepatic Overexpression of Hormone-sensitive Lipase and Adipose Triglyceride Lipase Promotes Fatty Acid Oxidation, Stimulates Direct Release of Free Fatty Acids, and Ameliorates Steatosis. J. Biol. Chem. 2008, 283, 13087–13099. [Google Scholar] [CrossRef] [Green Version]
- Esler, W.P.; Bence, K.K. Metabolic Targets in Nonalcoholic Fatty Liver Disease. Cell. Mol. Gastroenterol. Hepatol. 2019, 8, 247–267. [Google Scholar] [CrossRef] [Green Version]
- Liang, W.; Menke, A.L.; Driessen, A.; Koek, G.H.; Lindeman, J.H.; Stoop, R.; Havekes, L.M.; Kleemann, R.; van den Hoek, A.M. Establishment of a General NAFLD Scoring System for Rodent Models and Comparison to Human Liver Pathology. PLoS ONE 2014, 9, e115922. [Google Scholar] [CrossRef]
- Bolyen, E.; Rideout, J.R.; Dillon, M.R.; Bokulich, N.A.; Abnet, C.C.; Al-Ghalith, G.A.; Alexander, H.; Alm, E.J.; Arumugam, M.; Asnicar, F.; et al. Reproducible, Interactive, Scalable and Extensible Microbiome Data Science using QIIME 2. Nat. Biotechnol. 2019, 37, 852–857. [Google Scholar] [CrossRef] [PubMed]
- Wemheuer, F.; Taylor, J.A.; Daniel, R.; Johnston, E.; Meinicke, P.; Thomas, T.; Wemheuer, B. Tax4Fun2: Prediction of habitat-specific functional profiles and functional redundancy based on 16S rRNA gene sequences. Environ. Microbiome 2020, 15, 11. [Google Scholar] [CrossRef] [PubMed]
Groups | NFD | HFD | HFD + M-L | HFD + M-H | HFD + POST-L | HFD + POST-H |
---|---|---|---|---|---|---|
Macrovesicular steatosis score | 0 | 2 | 1 | 2 | 0 | 0 |
Microvesicular steatosis score | 0 | 3 | 3 | 3 | 1 | 0 |
Hypertrophy score | 0 | 2 | 2 | 1 | 0 | 0 |
Total steatosis score | 0 | 7 | 6 | 6 | 1 | 0 |
Inflammatory score | 0 | 1 | 1 | 1 | 0 | 0 |
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Pan, Z.; Mao, B.; Zhang, Q.; Tang, X.; Yang, B.; Zhao, J.; Cui, S.; Zhang, H. Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism. Int. J. Mol. Sci. 2022, 23, 13522. https://doi.org/10.3390/ijms232113522
Pan Z, Mao B, Zhang Q, Tang X, Yang B, Zhao J, Cui S, Zhang H. Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism. International Journal of Molecular Sciences. 2022; 23(21):13522. https://doi.org/10.3390/ijms232113522
Chicago/Turabian StylePan, Zhenghao, Bingyong Mao, Qiuxiang Zhang, Xin Tang, Bo Yang, Jianxin Zhao, Shumao Cui, and Hao Zhang. 2022. "Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism" International Journal of Molecular Sciences 23, no. 21: 13522. https://doi.org/10.3390/ijms232113522