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Selected Publication:
Aliwa, B.
Crosstalk Between Gut Microbiome Bile Acids and Metabolome in Sarcopenia in Liver Cirrhosis
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 121
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- Authors Med Uni Graz:
- Advisor:
- Horvath Angela
- Madl Tobias
- Stadlbauer-Köllner Vanessa
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- Abstract:
- Sarcopenia in liver cirrhosis is associated with low quality of life and high mortality risk. The pathogenesis has yet to be fully understood. We hypothesized that gut microbiome, bile acid composition, and metabolites differ between cirrhotic patients with and without sarcopenia and contribute to pathogenesis. Sarcopenia was diagnosed according to the European working group on sarcopenia in older people. Cirrhotic patients with (n=78) and without (n=38) sarcopenia and non-cirrhotic controls with (n=39) and without (n=20) sarcopenia. Fecal microbiome composition was studied by 16S rRNA sequencing, serum, and fecal bile acids (BAs) composition by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and metabolome composition in serum, feces, and urine by nuclear magnetic resonance (NMR). Bacteroides fragilis, Blautia Marseille, Sutterella spp, and Veillonella parvula were associated with cirrhotic patients with sarcopenia, whereas Bacteroides ovatus was more abundant in cirrhotic patients without sarcopenia. Similarly,Alistipes putredinis, Alistipes onderdonkii subspp vulgaris, Ruminococcaceae, Bacteroides coccae, and Eubacterium coprostanoligenes were associated with non-cirrhotic controls without sarcopenia We observed significantly elevated secondary (BAs), deoxycholic acid (DCA, p = 0.01), and lithocholic acid (LCA, p = 0.02), and the ratios of deoxycholic acid to cholic acid (DCA: CA, p = 0.04), lithocholic acid to chenodeoxycholic acid (LCA: CDCA, p = 0.03), and 12 alpha-hydroxylated to non-12 alpha-hydroxylated BAs (12 α-OH: non-12 α-OH BAs, p = 0.04) in serum of cirrhotic patients with sarcopenia compared to cirrhotic patients without sarcopenia indicating an enhanced transformation of primary to secondary (BAs) by the gut microbiome. Primary BAs CA (p = 0.02), ratios of CA: CDCA (p = 0.03), and total ursodeoxycholic acid to total secondary BAs (T-UDCA: total-sec-BAs, p = 0.03) were significantly reduced in the stool of cirrhotic patients with sarcopenia compared to cirrhotic without sarcopenia. Similarly, GDCA: DCA and GLCA: LCA were significantly increased in serum of non-cirrhotic control with sarcopenia than non-cirrhotic without sarcopenia. Also, valine and acetate were significantly reduced in the serum of cirrhotic patients with sarcopenia compared to cirrhotic patients without sarcopenia (p = 0.01 and p = 0.03, respectively). Multivariate logistic regression further confirmed the association of Bacteroides ovatus ( p = 0.01), ratios of CA: CDCA (p = 0.03), 12 α-OH: non-12 α-OH BAs (p = 0.04), T-UDCA: total-sec-BAs (p = 0.01), and serum valine (p = 0.04) with sarcopenia in liver cirrhosis even when corrected for the severity of liver disease and drug use. Our study suggests a potential functional gut microbiome-host interaction linking sarcopenia with the altered gut microbiome, bile acids profiles, and amino acids, pointing towards a possible mechanistic interplay in understanding sarcopenia pathogenesis.