Nitrogen recycling by the gut microbiome in sarcopenia

Rosa Haller^1,2Olha Hazia^1,2Nicole Feldbacher^1,2Julia Traub³Tobias Madl^4,5Hansjörg Habisch⁴Angela Horvath^1,2Vanessa Stadlbauer^1,2,5*

• ¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medizinische Universitat Graz, Graz, Austria
• ²CBmed GmbH, Graz, Austria
• ³Department of Clinical Medical Nutrition, Landeskrankenhaus-Universitatsklinikum Graz, Graz, Austria
• ⁴Otto Loewi Research Center, Medicinal Chemistry, Medizinische Universitat Graz, Graz, Austria
• ⁵BioTechMed-Graz Geschaftsstelle, Graz, Austria

Sarcopenia, defined as loss of skeletal muscle mass and strength, affects up to 70% of patients with liver cirrhosis. Since hibernating animals maintain muscle mass through microbial nitrogen recycling, urease-producing bacteria may have a protective role in humans. We hypothesized that altered microbial urease abundance contributes to differences in nitrogen recycling potential between patients with and without sarcopenia, with sex-specific effects. Stool samples from 152 patients with (n=101) and without sarcopenia (n=51) were analyzed. Functional profiles were predicted from 16S rRNA gene amplicon sequencing data using Tax4Fun2, and predicted abundances of urease subunit alpha were extracted. A systematic literature search identified 120 urease-producing taxa, of which 35 were represented in sequencing data. Sarcopenia is associated with a lower predicted abundance of urease subunit alpha in patients with cirrhosis (n=96; p=0.045, r=0.20; median=0.0002 vs. 0.0004), irrespective of sex, and in women (n=49, p=0.037, r=0.30, median=0.0002 vs. 0.0004), irrespective of cirrhosis. Urease subunit alpha abundance increases with the use of proton pump inhibitors (PPI) in the entire patient cohort (p=0.0028, r =0.24, median=0.0003 vs. 0.0002), patients with cirrhosis (p=0.033, r=0.22, median=0.0004 vs. 0.0002), and men (n=103, p=0.0005, r =0.34, median=0.0002 vs. 0.0001). Beta-blockers are associated with higher urease subunit alpha abundance in the entire patient cohort (p=0.018, r=0.19, median=0.0003 vs. 0.0002) and women (p=0.031, r=0.31, median=0.0004 vs. 0.0002). The overall abundance of potentially urease-producing taxa was comparable between the groups. The increased urease subunit alpha abundance in patients without sarcopenia, but with cirrhosis, and women, and the influence of medication on the abundance point towards potential additional effects of beta-blockers in sarcopenia.