pectins and Liver-Diseases--Alcoholic

Alterations in the composition of the gut microbiota (dysbiosis) are observed in nutritional liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) and have been shown to be associated with the severity of both. Editing the composition of the microbiota by fecal microbiota transfer or by application of probiotics or prebiotics/fiber in rodent models and human proof-of-concept trials of NAFLD and ALD have demonstrated its possible contribution to reducing the progression of liver damage. In this review, we address the role of a soluble fiber, pectin, in reducing the development of liver injury in NAFLD and ALD through its impact on gut bacteria.

Topics: Dysbiosis; Humans; Liver; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Pectins; Prebiotics; Probiotics

Reshaping the intestinal microbiota by the ingestion of fiber, such as pectin, improves alcohol-induced liver lesions in mice by modulating bacterial metabolites, including indoles, as well as bile acids (BAs). In this context, we aimed to elucidate how oral supplementation of pectin affects BA metabolism in alcohol-challenged mice receiving feces from patients with alcoholic hepatitis. Pectin reduced alcohol liver disease. This beneficial effect correlated with lower BA levels in the plasma and liver but higher levels in the caecum, suggesting that pectin stimulated BA excretion. Pectin modified the overall BA composition, favoring an augmentation in the proportion of hydrophilic forms in the liver, plasma, and gut. This effect was linked to an imbalance between hydrophobic and hydrophilic (less toxic) BAs in the gut. Pectin induced the enrichment of intestinal bacteria harboring genes that encode BA-metabolizing enzymes. The modulation of BA content by pectin inhibited farnesoid X receptor signaling in the ileum and the subsequent upregulation of Cyp7a1 in the liver. Despite an increase in BA synthesis, pectin reduced BA serum levels by promoting their intestinal excretion. In conclusion, pectin alleviates alcohol liver disease by modifying the BA cycle through effects on the intestinal microbiota and enhanced BA excretion.

Topics: Animals; Bile Acids and Salts; Gastrointestinal Microbiome; Humans; Liver Diseases, Alcoholic; Mice; Pectins

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Topics: Animals; Bacteroides; Ethanol; Inflammation; Liver; Liver Diseases, Alcoholic; Mice; Mice, Inbred C57BL; Pectins; Tryptophan

Chronic alcohol consumption is an important cause of liver-related deaths. Specific intestinal microbiota profiles are associated with susceptibility or resistance to alcoholic liver disease in both mice and humans. We aimed to identify the mechanisms by which targeting intestinal microbiota can improve alcohol-induced liver lesions.. We used human associated mice, a mouse model of alcoholic liver disease transplanted with the intestinal microbiota of alcoholic patients and used the prebiotic, pectin, to modulate the intestinal microbiota. Based on metabolomic analyses, we focused on microbiota tryptophan metabolites, which are ligands of the aryl hydrocarbon receptor (AhR). Involvement of the AhR pathway was assessed using both a pharmacological approach and AhR-deficient mice.. Pectin treatment modified the microbiome and metabolome in human microbiota-associated alcohol-fed mice, leading to a specific faecal signature. High production of bacterial tryptophan metabolites was associated with an improvement of liver injury. The AhR agonist Ficz (6-formylindolo (3,2-b) carbazole) reduced liver lesions, similarly to prebiotic treatment. Conversely, inactivation of the. Improvement of alcoholic liver disease by targeting the intestinal microbiota involves the AhR pathway, which should be considered as a new therapeutic target.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Carbazoles; Disease Models, Animal; Fecal Microbiota Transplantation; Feces; Female; Humans; Intestines; Liver Diseases, Alcoholic; Metabolome; Mice; Mice, Knockout; Microbiota; Pectins; Prebiotics; Receptors, Aryl Hydrocarbon; Tryptophan

Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD.. Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period.. Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis.. Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD.. Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human ALD through intestinal microbiota manipulation.

Topics: Animals; Bacteroides; Bile Acids and Salts; Dietary Fiber; Disease Models, Animal; Disease Susceptibility; Dysbiosis; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Humans; Liver Diseases, Alcoholic; Mice; Mice, Inbred C57BL; Pectins; Prebiotics