Intestinal Permeability in liver cirrhosis

Background  Previously, we could show that zonulin, a marker for intestinal permeability, is linked to a higher risk of mortality in cirrhotic patients. Microbiome analysis found that Phascolarctobacterium is associated with improved intestinal permeability and lower mortality. We aim to verify these results in a second, independent study cohort.

Materials and methods  Stool, serum and urine samples from 106 cirrhotic patients were obtained. Intestinal permeability was assessed by zonulin in stool. Group comparisons, Kaplan-Meier survival analysis and microbiome analysis with diversity metrics ANCOM and LEfSe was performed.

Results  Zonulin levels at baseline were able to predict mortality after 42 months (p  = 0.047). Microbiome analysis showed that Phascolarctobacterium was more abundant in patients with lower zonulin levels. Higher Phascolarctobacterium abundance was additionally associated with better hepatic function (higher total protein, higher fibrinogen levels, lower international normalized ratio, lower bilirubin levels (all p<0.05)) and a lower mortality over 36 months (p  = 0.028). Additionally to the previous study, higher Phascolarctobacterium abundance was associated with changes in the metabolome; lower stool succinate and glucose levels and higher serum glucose, urine phenylalanine and acetoacetate levels (all p<0.05) and changes in the bile acids composition; lower total primary bile acids, total glycoursodeoxycholic acid and a lower ratio of 12α hydroxylated bile acids to non 12α hydroxylated bile acids (all p<0.05).

Conclusions  We were able to verify the results from a previous analysis in a different cohort. Increased intestinal permeability is again linked to higher mortality and lower levels of Phascolarctobacterium. The genus can again be associated with better hepatic function and better chances of survival over 36 months. Phascolarctobacterium might have a positive effect on patients’ health by decreasing microbial succinate and producing short chain fatty acids and increasing its abundance could therefore be a novel therapeutic target to modulate the gut-liver axis.

Publikationsverlauf

Artikel online veröffentlicht:
24. Mai 2023