Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)

Overview

Journal GE Port J Gastroenterol

Specialty Gastroenterology

Date 2017 Sep 5

PMID 28868449

Citations 17

Authors

Helena Cortez-Pinto

Paula Borralho

Jorge Machado

Maria T Lopes

Ines V Gato

Antonio M Santos

Antonio S Guerreiro

Affiliations

Soon will be listed here.

Abstract

Background: Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis.

Aim: To clarify the potential effect of Synbiotic 2000Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia.

Methods: Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay - LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis.

Results: Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla and , either at 6 or 18 weeks; increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (-3.90). markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2).

Conclusion: Synbiotic 2000Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.

Citing Articles

Probiotic Supplementation Alleviates Corticosterone-Induced Fatty Liver Disease by Regulating Hepatic Lipogenesis and Increasing Gut Microbiota Diversity in Broilers.

Feng Y, Mei W, Chen Q, Chen X, Ni Y, Lei M Microorganisms. 2025; 13(1).

PMID: 39858968 PMC: 11767375. DOI: 10.3390/microorganisms13010200.

Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice.

Kochumon S, Malik M, Sindhu S, Arefanian H, Jacob T, Bahman F Nutrients. 2024; 16(12).

PMID: 38931284 PMC: 11207001. DOI: 10.3390/nu16121929.

Effect of Probiotic LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet.

Schmidt N, Molz P, Fraga B, Bondarczuk N, Silveira P, Ferri M Nutrients. 2024; 16(6).

PMID: 38542789 PMC: 10974660. DOI: 10.3390/nu16060879.

Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.

Zeng F, Su X, Liang X, Liao M, Zhong H, Xu J BMC Med. 2024; 22(1):104.

PMID: 38454425 PMC: 10921631. DOI: 10.1186/s12916-024-03317-y.

Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.

Maslennikov R, Poluektova E, Zolnikova O, Sedova A, Kurbatova A, Shulpekova Y Int J Mol Sci. 2023; 24(22).

PMID: 38003692 PMC: 10671141. DOI: 10.3390/ijms242216502.

References

Pandey K, Naik S, Vakil B . Probiotics, prebiotics and synbiotics- a review. J Food Sci Technol. 2015; 52(12):7577-87. PMC: 4648921. DOI: 10.1007/s13197-015-1921-1. View

Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L . Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. JPEN J Parenter Enteral Nutr. 2007; 31(2):119-26. DOI: 10.1177/0148607107031002119. View

Vespasiani-Gentilucci U, Carotti S, Perrone G, Mazzarelli C, Galati G, Onetti-Muda A . Hepatic toll-like receptor 4 expression is associated with portal inflammation and fibrosis in patients with NAFLD. Liver Int. 2014; 35(2):569-81. DOI: 10.1111/liv.12531. View

Backhed F, Ding H, Wang T, Hooper L, Koh G, Nagy A . The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004; 101(44):15718-23. PMC: 524219. DOI: 10.1073/pnas.0407076101. View

Amann R, Fuchs B, Behrens S . The identification of microorganisms by fluorescence in situ hybridisation. Curr Opin Biotechnol. 2001; 12(3):231-6. DOI: 10.1016/s0958-1669(00)00204-4. View

Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal W, Strowig T . Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012; 482(7384):179-85. PMC: 3276682. DOI: 10.1038/nature10809. View

Turroni F, Marchesi J, Foroni E, Gueimonde M, Shanahan F, Margolles A . Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J. 2009; 3(6):745-51. DOI: 10.1038/ismej.2009.19. View

Knight D, Gardiner D, Banks A, Snape S, Weston V, Bengmark S . Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial. Intensive Care Med. 2008; 35(5):854-61. DOI: 10.1007/s00134-008-1368-1. View

Harte A, da Silva N, Creely S, McGee K, Billyard T, Youssef-Elabd E . Elevated endotoxin levels in non-alcoholic fatty liver disease. J Inflamm (Lond). 2010; 7:15. PMC: 2873499. DOI: 10.1186/1476-9255-7-15. View

10.

Carr F, Chill D, Maida N . The lactic acid bacteria: a literature survey. Crit Rev Microbiol. 2003; 28(4):281-370. DOI: 10.1080/1040-840291046759. View

11.

Ferolla S, Armiliato G, Couto C, Ferrari T . The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease. Nutrients. 2014; 6(12):5583-99. PMC: 4276985. DOI: 10.3390/nu6125583. View

12.

Frasinariu O, Ceccarelli S, Alisi A, Moraru E, Nobili V . Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies. Dig Liver Dis. 2013; 45(7):543-51. DOI: 10.1016/j.dld.2012.11.010. View

13.

Ley R, Backhed F, Turnbaugh P, Lozupone C, Knight R, Gordon J . Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005; 102(31):11070-5. PMC: 1176910. DOI: 10.1073/pnas.0504978102. View

14.

Suarez-Zamorano N, Fabbiano S, Chevalier C, Stojanovic O, Colin D, Stevanovic A . Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nat Med. 2015; 21(12):1497-1501. PMC: 4675088. DOI: 10.1038/nm.3994. View

15.

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

16.

Farhadi A, Gundlapalli S, Shaikh M, Frantzides C, Harrell L, Kwasny M . Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. Liver Int. 2008; 28(7):1026-33. PMC: 4303249. DOI: 10.1111/j.1478-3231.2008.01723.x. View

17.

Imajo K, Fujita K, Yoneda M, Nozaki Y, Ogawa Y, Shinohara Y . Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab. 2012; 16(1):44-54. DOI: 10.1016/j.cmet.2012.05.012. View

18.

Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R . Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009; 49(6):1877-87. DOI: 10.1002/hep.22848. View

19.

Malkusch W, Rehn B, Bruch J . Advantages of Sirius Red staining for quantitative morphometric collagen measurements in lungs. Exp Lung Res. 1995; 21(1):67-77. DOI: 10.3109/01902149509031745. View

20.

Zhu L, Baker S, Gill C, Liu W, Alkhouri R, Baker R . Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2012; 57(2):601-9. DOI: 10.1002/hep.26093. View