Skip to main content

Advertisement

SpringerLink
Log in

The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently, Akkermansia muciniphila has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed A. muciniphila MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed A. muciniphila MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed A. muciniphila MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner (P < 0.0001), and significantly downregulated the expression of PPARγ (P < 0.0001). The heat-killed A. muciniphila MucT could significantly modulate the expression of fibrosis markers particularly in MOI 10 (P < 0.0001), and reversed the HSC activation in LPS-stimulated LX-2 cells. In conclusion, we demonstrated that heat-killed A. muciniphila MucT was safe and capable to ameliorate LPS-induced HSC activation through modulation of fibrosis markers. Further in vivo studies are required to validate the anti-fibrotic properties of heat-killed A. muciniphila MucT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Ottman N, Geerlings SY, Aalvink S, de Vos WM, Belzer C (2017) Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best Pract Res Clin Gastroenterol 31:637–642. https://doi.org/10.1016/j.bpg.2017.10.001

    Article  PubMed  Google Scholar 

  2. Ottman N, Davids M, Suarez-Diez M, Boeren S, Schaap PJ, Martins Dos Santos VAP, Smidt H, Belzer C et al (2017) Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol 83:e01014-e1017. https://doi.org/10.1128/aem

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G et al (2019) Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 25:1096–1103. https://doi.org/10.1038/s41591-019-0495-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD et al (2016) Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65:426–436. https://doi.org/10.1136/gutjnl-2014-308778

    Article  CAS  PubMed  Google Scholar 

  5. Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, Chen Y et al (2013) Human gut microbiota changes reveal the progression of glucose intolerance. PLoS ONE 8:e71108. https://doi.org/10.1371/journal.pone.0071108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA et al (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augmentin vitroutilization of mucin by other bacteria. Am J Gastroenterol 105:2420–2428. https://doi.org/10.1038/ajg.2010.281

    Article  CAS  PubMed  Google Scholar 

  7. Swidsinski A, Dörffel Y, Loening-Baucke V, Theissig F, Rückert JC, Ismail M, Rau WA et al (2011) Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum. Gut 60:34–40. https://doi.org/10.1136/gut.2009.191320

    Article  PubMed  Google Scholar 

  8. Derrien M, Van Baarlen P, Hooiveld G, Norin E, Muller M, de Vos WM (2011) Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol 2:166–180. https://doi.org/10.3389/fmicb.2011.00166

    Article  PubMed  PubMed Central  Google Scholar 

  9. Del Chierico F, Nobili V, Vernocchi P, Russo A, Stefanis CD, Gnani D, Furlanello C et al (2017) Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology 65:451–464. https://doi.org/10.1002/hep.28572

    Article  CAS  PubMed  Google Scholar 

  10. Özkul C, Yalınay M, Karakan T, Yılmaz G (2017) Determination of certain bacterial groups in gut microbiota and endotoxin levels in patients with nonalcoholic steatohepatitis. Turk J Gastroenterol 28:361–369. https://doi.org/10.5152/tjg.2017.17033

    Article  PubMed  Google Scholar 

  11. Grander C, Adolph TE, Wieser V, Lowe P, Wrzosek L, Gyongyosi B, Ward DV et al (2018) Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 67:891–901. https://doi.org/10.1136/gutjnl-2016-313432

    Article  CAS  PubMed  Google Scholar 

  12. Povero D, Pinatel EM, Leszczynska A, Goyal NP, Nishio T, Kim J, Kneiber D et al (2019) Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis. JCI Insight 5:e125652. https://doi.org/10.1172/jci.insight.125652

    Article  Google Scholar 

  13. Weiskirchen R, Weiskirchen S, Tacke F (2019) Organ and tissue fibrosis: molecular signals, cellular mechanisms and translational implications. Mol Aspects Med 65:2–15. https://doi.org/10.1016/j.mam.2018.06.003

    Article  CAS  PubMed  Google Scholar 

  14. Moreira RK (2007) Hepatic stellate cells and liver fibrosis. Arch Pathol Lab Med 131:1728–1734. https://doi.org/10.1043/1543-2165(2007)131[1728:HSCALF]2.0.CO;2

    Article  CAS  PubMed  Google Scholar 

  15. Shang L, Hosseini M, Liu X, Kisseleva T, Brenner DA (2018) Human hepatic stellate cell isolation and characterization. J Gastroenterol 53:6–17. https://doi.org/10.1007/s00535-017-1404-4

    Article  CAS  PubMed  Google Scholar 

  16. Deshpande G, Athalye-Jape G, Patole S (2018) Para-probiotics for preterm neonates-the next frontier. Nutrients 10:871. https://doi.org/10.3390/nu10070871

    Article  CAS  PubMed Central  Google Scholar 

  17. Adams CA (2010) The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev 23:37–46. https://doi.org/10.1017/S0954422410000090

    Article  CAS  PubMed  Google Scholar 

  18. Taverniti V, Guglielmetti S (2011) The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept). Genes Nutr 6:261–274. https://doi.org/10.1007/s12263-011-0218-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Piqué N, Berlanga M, Miñana-Galbis D (2019) Health benefits of heat-killed (tyndallized) probiotics: an overview. Int J Mol Sci 20:2534–2564. https://doi.org/10.3390/ijms20102534

    Article  CAS  PubMed Central  Google Scholar 

  20. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y et al (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS 110:9066–9071. https://doi.org/10.1073/pnas.1219451110

    Article  PubMed  Google Scholar 

  21. Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J et al (2017) A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 23:107–113. https://doi.org/10.1038/nm.4236

    Article  CAS  PubMed  Google Scholar 

  22. Derrien M, Vaughan EE, Plugge CM, de Vos WM (2004) Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol 54:1469–1476. https://doi.org/10.1099/ijs.0.02873-0

    Article  CAS  Google Scholar 

  23. Nakamoto N, Sasaki N, Aoki R, Miyamoto K, Suda W, Teratani T, Suzuki T et al (2019) Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat Microbiol 4:492–503. https://doi.org/10.1038/s41564-018-0333-1

    Article  CAS  PubMed  Google Scholar 

  24. Sun Q, Li F, Li H, Chen R-H, Gu Y-Z, Chen Y, Liang H-S et al (2015) Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair. Sci Rep 5:11560–11575. https://doi.org/10.1038/srep11560

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhao L, Ma R, Zhang L, Yuan X, Wu J, He L, Liu G et al (2019) Inhibition of HIF-1a-mediated TLR4 activation decreases apoptosis and promotes angiogenesis of placental microvascular endothelial cells during severe pre-eclampsia pathogenesis. Placenta 83:8–16. https://doi.org/10.1016/j.placenta.2019.06.375

    Article  CAS  PubMed  Google Scholar 

  26. Parola M, Pinzani M (2019) Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med 65:37–55. https://doi.org/10.1016/j.mam.2018.09.002

    Article  CAS  PubMed  Google Scholar 

  27. Higashi T, Friedman SL, Hoshida Y (2017) Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 121:27–42. https://doi.org/10.1016/j.addr.2017.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kitano M, Bloomston PM (2016) Hepatic stellate cells and microRNAs in pathogenesis of liver fibrosis. J Clin Med 5:38–57. https://doi.org/10.3390/jcm5030038

    Article  CAS  PubMed Central  Google Scholar 

  29. Albillos A, de Gottardi A, Rescigno M (2020) The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol 72:558–577. https://doi.org/10.1016/j.jhep.2019.10.003

    Article  CAS  PubMed  Google Scholar 

  30. Zhou R, Fan X, Schnabl B (2019) Role of the intestinal microbiome in liver fibrosis development and new treatment strategies. Transl Res 209:22–38. https://doi.org/10.1016/j.jhep.2019.10.003

    Article  CAS  PubMed  Google Scholar 

  31. Safari Z, Gérard P (2019) The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci 76:1541–1558. https://doi.org/10.1007/s00018-019-03011-w

    Article  CAS  PubMed  Google Scholar 

  32. Hollister EB, Gao C, Versalovic J (2014) Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology 146:1449–1458. https://doi.org/10.1053/j.gastro.2014.01.052

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cani PD, de Vos WM (2017) Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol 8:1765–1773. https://doi.org/10.3389/fmicb.2017.01765

    Article  PubMed  PubMed Central  Google Scholar 

  34. Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, Bang C et al (2019) Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe 26:252-264.e210. https://doi.org/10.5005/jp-journals-10018-1233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nistal E, Saenz de Miera LE, Ballesteros Pomar M, Sánchez Campos S, García Mediavilla MV, Álvarez Cuenllas B, Linares P et al (2019) An altered fecal microbiota profile in patients with non-alcoholic fatty liver disease (NAFLD) associated with obesity. Rev Esp Enferm Dig 111:275–282. https://doi.org/10.17235/reed.2019.6068/2018

    Article  PubMed  Google Scholar 

  36. Addolorato G, Ponziani FR, Dionisi T, Mosoni C, Vassallo GA, Sestito L, Petito V et al (2020) Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol-associated liver disease. Liver Int 40:878–888. https://doi.org/10.1111/liv.14383

    Article  CAS  PubMed  Google Scholar 

  37. Lavekar AS, Raje DV, Manohar T, Lavekar AA (2017) Role of probiotics in the treatment of nonalcoholic fatty liver disease: a meta-analysis. Euroasian J Hepatogastroenterol 7:130–137. https://doi.org/10.5005/jp-journals-10018-1233

    Article  Google Scholar 

  38. Liu Y, Chen K, Li F, Gu Z, Liu Q, He L, Shao T et al (2019) Probiotic LGG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice. Hepatology 7:2050–2066. https://doi.org/10.1002/hep.30975

    Article  CAS  Google Scholar 

  39. Ahn SB, Jun DW, Kang B-K, Lim JH, Lim S, Chung M-J (2019) Randomized, double-blind, placebo-controlled study of a multispecies probiotic mixture in nonalcoholic fatty liver disease. Sci Rep 9:5688–5697. https://doi.org/10.1038/s41598-019-42059-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. O’neill LA, Golenbock D, Bowie AG, (2013) The history of toll-like receptors-redefining innate immunity. Nat Rev Immunol 13:453–460. https://doi.org/10.1038/nri3446

    Article  CAS  Google Scholar 

  41. Seki E, De Minicis S, Österreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF (2007) TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat Med 13:1324–1332. https://doi.org/10.1038/nm1663

    Article  CAS  PubMed  Google Scholar 

  42. Kim SY, Seki E (2020) Toll‐like receptors in liver disease. In: The liver: biology and pathobiology (ed), 6th edn. John Wiley & Sons Ltd, pp 737–746. https://doi.org/10.1002/9781119436812.ch57

  43. Ouyang Y, Guo J, Lin C, Lin J, Cao Y, Zhang Y, Wu Y et al (2016) Transcriptomic analysis of the effects of toll-like receptor 4 and its ligands on the gene expression network of hepatic stellate cells. Fibrogenesis Tissue Repair 9:2. https://doi.org/10.1186/s13069-016-0039-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yuan Y, Han Q, Li S, Tian Z, Zhang J (2017) Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling. Sci Rep 7:3952. https://doi.org/10.1038/s41598-017-04374-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ottman N, Reunanen J, Meijerink M, Pietilä TE, Kainulainen V, Klievink J, Huuskonen L et al (2017) Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12:e0173004-e173022. https://doi.org/10.1371/journal.pone.0173004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ashrafian F, Shahryari A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, Hadifar S (2019) Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 10:2155–2171. https://doi.org/10.3389/fmicb.2019.02155

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hänninen A, Toivonen R, Pöysti S, Belzer C, Plovier H, Ouwerkerk JP, Emani R (2018) Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut 67:1445–1453. https://doi.org/10.1136/gutjnl-2017-314508

    Article  CAS  PubMed  Google Scholar 

  48. Tsuchida T, Friedman SL (2017) Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol 14:397–411. https://doi.org/10.1038/nrgastro.2017.38

    Article  CAS  PubMed  Google Scholar 

  49. Kesar V, Odin JA (2014) Toll-like receptors and liver disease. Liver Int 34:184–196. https://doi.org/10.1111/liv.12315

    Article  CAS  PubMed  Google Scholar 

  50. Park YJ, Kim DM, Jeong MH, Yu JS, So HM, Bang IJ, Kim HR et al (2020) (-)-Catechin-7-O-β-d-apiofuranoside inhibits hepatic stellate cell activation by suppressing the stat3 signaling pathway. Cells 9:30–47. https://doi.org/10.3390/cells9010030

    Article  CAS  Google Scholar 

  51. Zhang C-Y, Yuan W-G, He P, Lei J-H, Wang C-X (2016) Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 22:10512–10522. https://doi.org/10.3748/wjg.v22.i48.10512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Jantararussamee C, Rodniem S, Taweechotipatr M, Showpittapornchai U, Pradidarcheep W (2020) Hepatoprotective effect of probiotic lactic acid bacteria on thioacetamide-induced liver fibrosis in rats. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-020-09663-6

    Article  Google Scholar 

  53. Wu W, Lv L, Shi D, Ye J, Fang D, Guo F, Li Y et al (2017) Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model. Front Microbiol 8:1804–1817. https://doi.org/10.3389/fmicb.2017.01804

    Article  PubMed  PubMed Central  Google Scholar 

  54. Tanaka N, Aoyama T, Kimura S, Gonzalez FJ (2017) Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol Ther 179:142–157. https://doi.org/10.1016/j.pharmthera.2017.05.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rudraiah S, Zhang X, Wang L (2016) Nuclear receptors as therapeutic targets in liver disease: are we there yet? Annu Rev Pharmacol Toxicol 56:605–626. https://doi.org/10.1146/annurev-pharmtox-010715-103209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Choi JH, Kim SM, Lee GH, Jin SW, Lee HS, Chung YC, Jeong HG (2019) Platyconic acid a, platycodi radix-derived saponin, suppresses TGF-β1-induced activation of hepatic stellate cells via blocking SMAD and activating the PPARγ signaling pathway. Cells 8:1544–1560. https://doi.org/10.3390/cells8121544

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all laboratory staff of Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran, and Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran. This article has been also extracted from a PhD thesis (Registration No: B-9428) from Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Tehran, Iran.

Funding

The study was funded by a research grant (Project No: RIGLD 1017) from Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Shahrbanoo Keshavarz Azizi Raftar, Farzam Vaziri & Seyed Davar Siadat

  2. Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Tehran, Iran

    Shahrbanoo Keshavarz Azizi Raftar, Farzam Vaziri & Seyed Davar Siadat

  3. Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Shahrbanoo Keshavarz Azizi Raftar, Masoumeh Azimirad & Abbas Yadegar

  4. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sara Abdollahiyan

  5. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Arfa Moshiri & Mohammad Reza Zali

  6. Experimental Therapy Unit, Laboratory of Oncology, G. Gaslini Children’s Hospital, Genoa, Italy

    Arfa Moshiri

Authors
  1. Shahrbanoo Keshavarz Azizi Raftar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Abdollahiyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masoumeh Azimirad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abbas Yadegar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farzam Vaziri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arfa Moshiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seyed Davar Siadat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SKAR performed the microbiological experiments, cell culture, molecular tests, data analysis, and wrote the manuscript draft; SA participated in molecular testing; MA contributed to microbiological experiments and cell culture experiments; AY, SDS, and MRZ contributed to study design, methodology, conceptualization, and project administration; AY critically revised the manuscript; FV and AM participated in manuscript revision. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Abbas Yadegar.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This work does not contain any studies related with human participants or animals. The study was approved by the Institutional Ethical Review Committee of Research Institute for Gastroenterology and Liver Diseases at Shahid Beheshti University of Medical Sciences (Project No. IR.SBMU.RIGLD.REC.1395.211).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keshavarz Azizi Raftar, S., Abdollahiyan, S., Azimirad, M. et al. The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells. Probiotics & Antimicro. Prot. 13, 776–787 (2021). https://doi.org/10.1007/s12602-020-09733-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-020-09733-9

Keywords

Search

Navigation