Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis
2
조회
0
다운로드
5
인용
0
참고문헌
키워드
초록
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions: Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.
Abstract
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions: Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.
참고문헌 (50)
- Ascha MS, "The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis", Hepatology, 51, pp.1972~1978 (2010)
- Qin J, "A human gut microbial gene catalogue established by metagenomic sequencing", Nature, 464, pp.59~65 (2010)
- Joseph F. Cavallari, "Intestinal Microbiota Contributes to Energy Balance, Metabolic Inflammation, and Insulin Resistance in Obesity", Journal of Obesity & Metabolic Syndrome, 26(3), pp.161~171 (2017), 대한비만학회
- Aragonès G, "Gut microbiota-derived mediators as potential markers in nonalcoholic fatty liver disease", Biomed Res Int, 2019, pp.8507583~ (2019)
- Takiishi T, "Intestinal barrier and gut microbiota: shaping our immune responses throughout life", Tissue Barriers, 5, pp.e1373208~ (2017)
- Belkaid Y, "Role of the microbiota in immunity and inflammation", Cell, 157, pp.121~141 (2014)
- Lee NY, "Lactobacillus and Pediococcus ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome", Gut Microbes, 11, pp.882~899 (2020)
- Ohtani N, "Role of the gut-liver axis in liver inflammation, fibrosis, and cancer: a special focus on the gut microbiota relationship", Hepatol Commun, 3, pp.456~470 (2019)
- Saltzman ET, "Intestinal microbiome shifts, dysbiosis, inflammation, and non-alcoholic fatty liver disease", Front Microbiol, 9, pp.61~ (2018)
- Walenbergh SM, "Cholesterol is a significant risk factor for non-alcoholic steatohepatitis", Expert Rev Gastroenterol Hepatol, 9, pp.1343~1346 (2015)
- Griffin EE, "Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells", J Lipid Res, 46, pp.2052~2060 (2005)
- Baratta F, "Reduced lysosomal acid lipase activity in adult patients with non-alcoholic fatty liver disease", EBioMedicine, 2, pp.750~754 (2015)
- 홍이판, "Different Immune Regulatory Potential of Lactobacillus plantarum and Lactobacillus sakei Isolated from Kimchi", Journal of Microbiology and Biotechnology, 24(12), pp.1629~1635 (2014), 한국미생물·생명공학회[DOI]
- Uchinaka A, "Anti-inflammatory effects of heat-killed Lactobacillus plantarum L-137 on cardiac and adipose tissue in rats with metabolic syndrome", Sci Rep, 8, pp.8156~ (2018)
- Matuchansky C, "Anti-inflammatory lactobacilli: strain specificity", Gut, 61, pp.786~ (2012)
- Wong VW, "Treatment of nonalcoholic steatohepatitis with probiotics. A proofof-concept study", Ann Hepatol, 12, pp.256~262 (2013)
- 백정기, "Can Gut Microbiota Modulation Be Used as a Practical Treatment for Obesity?", Journal of Obesity & Metabolic Syndrome, 27(2), pp.75~77 (2018), 대한비만학회
- Yoon SH, "Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies", Int J Syst Evol Microbiol, 67, pp.1613~1617 (2017)
- Edgar RC, "Search and clustering orders of magnitude faster than BLAST", Bioinformatics, 26, pp.2460~2461 (2010)
- Xie JT, "Antioxidant effects of ginsenoside Re in cardiomyocytes", Eur J Pharmacol, 532, pp.201~207 (2006)
- Nyblom H, "The AST", ALT ratio as an indicator of cirrhosis in patients with PBC, 2006, pp.26, 840~845
- Bahl MI, "Freezing fecal samples prior to DNA extraction affects the Firmicutes to Bacteroidetes ratio determined by downstream quantitative PCR analysis", FEMS Microbiol Lett, 329, pp.193~197 (2012)
- Bugianesi E, "Expanding the natural history of nonalcoholic steatohepatitis:from cryptogenic cirrhosis to hepatocellular carcinoma", Gastroenterology, 123, pp.134~140 (2002)
- Betrapally NS, "Gut microbiome and liver disease", Transl Res, 179, pp.49~59 (2017)
- Arguello G, "Recent insights on the role of cholesterol in non-alcoholic fatty liver disease", Biochim Biophys Acta, 1852, pp.1765~1778 (2015)
- Tomita K, "Free cholesterol accumulation in hepatic stellate cells: mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice", Hepatology, 59, pp.154~169 (2014)
- Liong MT, "Effects of a synbiotic containing Lactobacillus acidophilus ATCC 4962 on plasma lipid profiles and morphology of erythrocytes in hypercholesterolaemic pigs on highand low-fat diets", Br J Nutr, 98, pp.736~744 (2007)
- Simons LA, "Effect of Lactobacillus fermentum on serum lipids in subjects with elevated serum cholesterol", Nutr Metab Cardiovasc Dis, 16, pp.531~535 (2006)
- Tuddenham S, "The intestinal microbiome and health", Curr Opin Infect Dis, 28, pp.464~470 (2015)
- Ley RE, "Microbial ecology: human gut microbes associated with obesity", Nature, 444, pp.1022~1023 (2006)
- Schwenger KJ, "The role of the gut microbiome in chronic liver disease: the clinical evidence revised", JHEP Rep, 1, pp.214~226 (2019)
- Liu C, "Treatment with 20(S)-ginsenoside Rg3 reverses multidrug resistance in A549", DDP xenograft tumors, 2018, pp.15, 4376~4382
- Konturek PC, "Gut–liver axis: how do gut bacteria influence the liver?", Med Sci (Basel), 6, pp.79~ (2018)
- Ma X, "Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells", J Hepatol, 49, pp.821~830 (2008)
- Park SS, "Lactobacillus acidophilus NS1 attenuates diet-induced obesity and fatty liver", J Endocrinol, 237, pp.87~100 (2018)
- PARK, YOO HEON, "Effect of Dietary Inclusion of Lactobacillus acidophilus ATCC 43121 onCholesterol Metabolism in Rats", Journal of Microbiology and Biotechnology, 17(4), pp.655~662 (2007), 한국미생물·생명공학회
- Song M, "Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice", J Dairy Sci, 98, pp.1492~1501 (2015)
- Palaniyandi SA, "Probiotic characterization of cholesterol-lowering Lactobacillus fermentum MJM60397", Probiotics Antimicrob Proteins, 12, pp.1161~1172 (2020)
- 김병국, "Protective Effect of Lactobacillus fermentum LA12 in an Alcohol-Induced Rat Model of Alcoholic Steatohepatitis", 한국축산식품학회지, 37(6), pp.931~939 (2017), 한국축산식품학회
- Aronsson L, "Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4)", PLoS One, 5, pp.e13087~ (2010)
- 강다영, "Anti-Obesity Effects of a Mixture of Fermented Ginseng, Bifidobacterium longum BORI, and Lactobacillus paracasei CH88 in High-Fat Diet-Fed Mice", Journal of Microbiology and Biotechnology, 28(5), pp.688~696 (2018), 한국미생물·생명공학회
- Fuentes MC, "Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults", Br J Nutr, 109, pp.1866~1872 (2013)
- Li C, "Lactobacillus plantarum NCU116 improves liver function, oxidative stress and lipid metabolism in rats with high fat diet induced non-alcoholic fatty liver disease", Food Funct, 5, pp.3216~3223 (2014)
- Rinninella E, "What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases", Microorganisms, 7, pp.14~ (2019)
- Niederreiter L, "Cytokines and fatty liver diseases", Liver Research, 2, pp.14~20 (2018)
- Caricilli AM, "The role of gut microbiota on insulin resistance", Nutrients, 5, pp.829~851 (2013)
- You JS, "Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine", Microbiome, 7, pp.132~ (2019)
- Bogatyrev SR, "Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine", Microbiome, 8, pp.19~ (2020)
- Guandalini S, "Probiotics for prevention and treatment of diarrhea", J Clin Gastroenterol, 45(Suppl), pp.S149~S153 (2011)
- Wang J, "Probiotic Lactobacillus plantarum promotes intestinal barrier function by strengthening the epithelium and modulating gut microbiota", Front Microbiol, 9, pp.1953~ (2018)
