Gut Microbiota and Metabolites of Cirrhotic Portal Hypertension: a Novel Target on the Therapeutic Regulation

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2024 Jul 19

PMID 39028343

Authors

Yarong Hao

Zhiyuan Hao

Xin Zeng

Yong Lin

Affiliations

Soon will be listed here.

Abstract

Background: The regulatory role of gut microbiota and gut-derived metabolites through the gut-liver axis in the development of cirrhotic portal hypertension (PH) has received increasing attention.

Methods: The review summarized a series of investigations on effects of metabolites derived from microbiota and medicines targeting microbiome including rifaximin, VSL#3, statins, propranolol, FXR agonists as well as drugs derived from bile acids (BAs) on PH progression.

Results: Patients with PH exhibit alterations in gut microbial richness and differential overall microbiota community, and several results clearly displayed the correlation of PH with enrichment of Veillonella dispar or depletion of Clostridiales, Peptostreptococcaceae, Alistipes putredinis, Roseburia faecis and Clostridium cluster IV. The gut-derived metabolites including hydrogen sulfide, tryptophan metabolites, butyric acid, secondary BAs and phenylacetic acid (PAA) participate in a range of pathophysiology process of PH through modulating intrahepatic vascular resistance and portal blood flow associated with the formation and progression of PH. Established and emerging drugs targeting on bacterial translocation and intestinal eubiosis are gradually identified as potential strategies for treatments of liver cirrhosis and PH by modulating intestinal inflammation, splanchnic arterial vasodilation and endothelial dysfunction.

Conclusions: Future explorations should further characterize the alteration of the fecal microbiome and metabolite profiles in PH and elucidate the regulatory mechanism of the intestinal microbiome, gut-derived metabolites and gut microbiota targeted pharmaceutical treatments involved in PH.

References

Gines P, Krag A, Abraldes J, Sola E, Fabrellas N, Kamath P . Liver cirrhosis. Lancet. 2021; 398(10308):1359-1376. DOI: 10.1016/S0140-6736(21)01374-X. View

Gracia-Sancho J, Marrone G, Fernandez-Iglesias A . Hepatic microcirculation and mechanisms of portal hypertension. Nat Rev Gastroenterol Hepatol. 2018; 16(4):221-234. DOI: 10.1038/s41575-018-0097-3. View

Jalan R, DAmico G, Trebicka J, Moreau R, Angeli P, Arroyo V . New clinical and pathophysiological perspectives defining the trajectory of cirrhosis. J Hepatol. 2021; 75 Suppl 1:S14-S26. DOI: 10.1016/j.jhep.2021.01.018. View

Nicholson J, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W . Host-gut microbiota metabolic interactions. Science. 2012; 336(6086):1262-7. DOI: 10.1126/science.1223813. View

Rooks M, Garrett W . Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016; 16(6):341-52. PMC: 5541232. DOI: 10.1038/nri.2016.42. View

DeBerardinis R, Keshari K . Metabolic analysis as a driver for discovery, diagnosis, and therapy. Cell. 2022; 185(15):2678-2689. PMC: 9469798. DOI: 10.1016/j.cell.2022.06.029. View

Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L . Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014; 513(7516):59-64. DOI: 10.1038/nature13568. View

Albillos A, De Gottardi A, Rescigno M . The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol. 2019; 72(3):558-577. DOI: 10.1016/j.jhep.2019.10.003. View

Tilg H, Adolph T, Trauner M . Gut-liver axis: Pathophysiological concepts and clinical implications. Cell Metab. 2022; 34(11):1700-1718. DOI: 10.1016/j.cmet.2022.09.017. View

10.

Gedgaudas R, Bajaj J, Skieceviciene J, Varkalaite G, Jurkeviciute G, Gelman S . Circulating microbiome in patients with portal hypertension. Gut Microbes. 2022; 14(1):2029674. PMC: 8824227. DOI: 10.1080/19490976.2022.2029674. View

11.

Yokoyama K, Tsuchiya N, Yamauchi R, Miyayama T, Uchida Y, Shibata K . Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension. Intern Med. 2020; 59(17):2089-2094. PMC: 7516306. DOI: 10.2169/internalmedicine.4628-20. View

12.

Ye J, Lv L, Wu W, Li Y, Shi D, Fang D . Butyrate Protects Mice Against Methionine-Choline-Deficient Diet-Induced Non-alcoholic Steatohepatitis by Improving Gut Barrier Function, Attenuating Inflammation and Reducing Endotoxin Levels. Front Microbiol. 2018; 9:1967. PMC: 6111843. DOI: 10.3389/fmicb.2018.01967. View

13.

Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V . A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2013; 63(8):1275-83. DOI: 10.1136/gutjnl-2013-304833. View

14.

Pignatelli P, Fabietti G, Ricci A, Piattelli A, Curia M . How Periodontal Disease and Presence of Nitric Oxide Reducing Oral Bacteria Can Affect Blood Pressure. Int J Mol Sci. 2020; 21(20). PMC: 7589924. DOI: 10.3390/ijms21207538. View

15.

Stojanov S, Berlec A, Strukelj B . The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms. 2020; 8(11). PMC: 7692443. DOI: 10.3390/microorganisms8111715. View

16.

Wu Z, Zhou H, Liu D, Deng F . Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis. Front Cell Infect Microbiol. 2023; 13:1218552. PMC: 10361729. DOI: 10.3389/fcimb.2023.1218552. View

17.

Teltschik Z, Wiest R, Beisner J, Nuding S, Hofmann C, Schoelmerich J . Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense. Hepatology. 2011; 55(4):1154-63. DOI: 10.1002/hep.24789. View

18.

Moghadamrad S, McCoy K, Geuking M, Sagesser H, Kirundi J, Macpherson A . Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels. Hepatology. 2015; 61(5):1685-95. DOI: 10.1002/hep.27698. View

19.

Hassan M, Moghadamrad S, Sorribas M, Muntet S, Kellmann P, Trentesaux C . Paneth cells promote angiogenesis and regulate portal hypertension in response to microbial signals. J Hepatol. 2020; 73(3):628-639. DOI: 10.1016/j.jhep.2020.03.019. View

20.

Huang H, Tsai M, Chang C, Pun C, Huang Y, Hou M . Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats. Clin Sci (Lond). 2021; 135(24):2709-2728. DOI: 10.1042/CS20210602. View