Nitrogen recycling by the gut microbiome in sarcopenia

Background:  Sarcopenia is the loss of skeletal muscle mass and strength, and affects up to 70% of patients with cirrhosis. Since many mammals survive hibernation without muscle loss, they are often studied in the context of sarcopenia. It was shown that the abundance of urease-producing bacteria is increased in squirrels during hibernation and that the nitrogen produced is integrated into muscle protein. Due to this finding, we aimed to gain a better understanding of nitrogen recycling potential in sarcopenia with a special focus on sex-specific differences since cirrhosis and sarcopenia have a male predominance.

Materials and methods:  Stool samples of 152 patients (96 cirrhotics, 56 non-cirrhotics) with and without sarcopenia were obtained. We predicted the functional profiles of microbial communities based on 16S rRNA sequencing data (Tax4Fun2) and extracted the predicted abundance of urease subunits (alpha, beta, gamma). Additionally, we performed a systematic literature search to identify urease-producing taxa and extracted their abundance from 16S rRNA sequencing data to compare them between patients with and without sarcopenia

Results:  Sarcopenia, but not cirrhosis nor sex was associated with lower urease gene abundance.In women irrespective of cirrhosis (n=49; 28 sarcopenic) and in patients with cirrhosis (n=64; p<0.05) gene abundance of urease subunits was lower in sarcopenic patients, irrespective of sex. The systematic literature search yielded 120 taxa, of which 35 were present in sequencing data. Overall abundance of potentially urease-producing taxa was comparable between the groups with only slight and divergent differences in abundance of Bacteroides fragilis, Micrococcaceae and Clostridiaceae 1 .

Conclusions:  We found lower levels of predicted urease gene abundance in patients with sarcopenia. This gives the first indications for the potential role of the gut microbiome and the potential for nitrogen recycling in sarcopenia. More pronounced differences in women and patients with cirrhosis, two groups disproportionally affected by sarcopenia, point towards a potential precision medicine target.

Publikationsverlauf

Artikel online veröffentlicht:
05. Juni 2024