Gut microbiota and host metabolism in liver cirrhosis

Abstract

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients.

Keywords: Fatty acids; Liver cirrhosis; Metabolism; Microbiota; Probiotics.

Figure 1

Correlation networks among fecal microflora and organic acid and serum organic and fatty acid concentrations in hepatic cancer patients. Square boxes indicate fecal components and ellipsoids indicate serum components. Solid lines indicate positive correlations and dotted lines indicate negative correlations. A: Normal liver group; B: Chronic hepatitis or liver fibrosis group; C: Liver cirrhosis group. ^aP < 0.05 and ^bP < 0.01 by Pearson’s correlation coefficient test. Bact: Bacteroidaceae; Bifi: Bifidobacterium; Lact: Lactobacillus; Enteroba: Enterobacteriaceae; Enteroco: Enterococcus; Cand: Candida; C1: Formic acid; C2: Acetic acid; C3: Propionic acid; C4: Butyric acid; AA: Arachidonic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; FFA: Free fatty acid; PL: Phospholipid. Data adapted from Usami et al[46].

Figure 2

Sub-networks showing correlation network differences from baseline to week 8 in placebo and in Lactobacillus GG groups separately centered on selected bacterial taxa. Color of nodes: Blue, inflammatory cytokine; light green, serum metabolites; dark green, urine metabolites. Color of edges: pink, negative remained negative but there is a net loss of negative correlation; dark blue, negative changed to positive; yellow, positive remained positive but there is a net loss of positive correlation; red, positive to negative; dark green, complete shift of negative to positive; military green, complete shift of positive to negative. A, B: Sub-networks of correlation changes centered around Enterobacteriaceae; C, D: Sub-networks of correlation changes centered around Clostridiales Incertae Sedis XIV; E, F: Sub-networks of correlation changes centered around Ruminococcaceae; G, H: Sub-networks of correlation changes centered around Lachnospiraceae. NSE: Neuron-specific enolase; IL: Interleukin; IFN: Interferon; LysoPC: Lysophosphatidylcholine; LysoPE: Lysophosphatidylethanolamine; ADMA: Asymmetricdimethylarginine; Rumino: Ruminococcaceae. Data adapted from Bajaj et al[69].