Advertisement

Microbiota in Non-alcoholic Liver Disease

  • Yuji OgawaEmail author
  • Yasushi Honda
  • Takaomi Kessoku
  • Wataru Tomeno
  • Kento Imajo
  • Masato Yoneda
  • Satoru Saito
  • Atsushi Nakajima
Chapter

Abstract

The liver is exposed to large amounts of bacterial components and metabolites from the intestine. The gut microbiota has recently evolved as an important player in the gut-liver axis. Various liver disorders, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and primary sclerosing cholangitis, have been reported to be associated with alterations of the gut microbiota. Dysbiosis and a leaky gut are believed to be involved in the pathophysiology of many liver diseases through multiple interactions with the host’s immune system and other cell types. Furthermore, it is believed that hyperresponsiveness of the liver to low-dose lipopolysaccharides arriving from the intestine through the portal vein accelerates the pathophysiology of NAFLD. The short-chain fatty acids produced by gut microorganisms are speculated to contribute to liver disease progression via multiple mechanisms. A number of trials focusing on the gut microbiota are currently ongoing. A greater understanding in the future of the involvement of gut microbiota and its components in the pathogenesis of liver diseases might pave the way for the development of novel therapies for these diseases.

Keywords

Microbiota Non-alcoholic fatty liver disease Primary sclerosing cholangitis 

References

  1. 1.
    Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65–80.CrossRefGoogle Scholar
  2. 2.
    Betrapally NS, Gillevet PM, Bajaj JS. Changes in the intestinal microbiome and alcoholic and nonalcoholic liver diseases: causes or effects? Gastroenterology. 2016;150:1745–1755.e1743.CrossRefGoogle Scholar
  3. 3.
    Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787–803.CrossRefGoogle Scholar
  4. 4.
    Gonzalez FJ, Jiang C, Patterson AD. An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease. Gastroenterology. 2016;151:845–59.CrossRefGoogle Scholar
  5. 5.
    Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13:412–25.CrossRefGoogle Scholar
  6. 6.
    Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, Quraishi MN, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2016;65:330–9.CrossRefGoogle Scholar
  7. 7.
    Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 2018;68:280–95.CrossRefGoogle Scholar
  8. 8.
    Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014;146:1513–24.CrossRefGoogle Scholar
  9. 9.
    Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut. 2016;65:2035–44.CrossRefGoogle Scholar
  10. 10.
    Wiest R, Albillos A, Trauner M, Bajaj JS, Jalan R. Targeting the gut-liver axis in liver disease. J Hepatol. 2017;67:1084–103.CrossRefGoogle Scholar
  11. 11.
    Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, Srishord M. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore). 2012;91:319–27.CrossRefGoogle Scholar
  12. 12.
    Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001;48:206–11.CrossRefGoogle Scholar
  13. 13.
    Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33:2277–84.CrossRefGoogle Scholar
  14. 14.
    Rivera LR, Leung C, Pustovit RV, Hunne BL, Andrikopoulos S, Herath C, Testro A, et al. Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet. Neurogastroenterol Motil. 2014;26:1188–99.CrossRefGoogle Scholar
  15. 15.
    Saito T, Hayashida H, Furugen R. Comment on: Cani et al. (2007) Metabolic endotoxemia initiates obesity and insulin resistance: Diabetes 56:1761-1772. Diabetes. 2007;56:e20; author reply e21CrossRefGoogle Scholar
  16. 16.
    Szabo G, Iracheta-Vellve A. Inflammasome activation in the liver: focus on alcoholic and non-alcoholic steatohepatitis. Clin Res Hepatol Gastroenterol. 2015;39(Suppl 1):S18–23.CrossRefGoogle Scholar
  17. 17.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.CrossRefGoogle Scholar
  18. 18.
    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.CrossRefGoogle Scholar
  19. 19.
    Imajo K, Fujita K, Yoneda M, Nozaki Y, Ogawa Y, Shinohara Y, Kato S, et al. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab. 2012;16:44–54.CrossRefGoogle Scholar
  20. 20.
    Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol. 2009;11:2112–22.CrossRefGoogle Scholar
  21. 21.
    Macfarlane GT, Macfarlane S. Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol. 2011;45(Suppl):S120–7.CrossRefGoogle Scholar
  22. 22.
    Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451–5.CrossRefGoogle Scholar
  23. 23.
    Windey K, de Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012;56:184–96.CrossRefGoogle Scholar
  24. 24.
    Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84.CrossRefGoogle Scholar
  25. 25.
    Quraishi MN, Sergeant M, Kay G, Iqbal T, Chan J, Constantinidou C, Trivedi P, et al. The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. Gut. 2017;66:386–8.CrossRefGoogle Scholar
  26. 26.
    Bjornsson E, Cederborg A, Akvist A, Simren M, Stotzer PO, Bjarnason I. Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis. Scand J Gastroenterol. 2005;40:1090–4.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Yuji Ogawa
    • 1
    Email author
  • Yasushi Honda
    • 1
  • Takaomi Kessoku
    • 1
  • Wataru Tomeno
    • 1
  • Kento Imajo
    • 1
  • Masato Yoneda
    • 1
  • Satoru Saito
    • 1
  • Atsushi Nakajima
    • 1
  1. 1.Department of Gastroenterology and HepatologyYokohama City University Graduate School of MedicineYokohamaJapan

Personalised recommendations