Sarcopenia: gut microbiota involved in the loss of skeletal muscle mass and function?

With life expectancy getting longer, scientific research is increasingly interested in health conditions linked to old age. Among them is sarcopenia, a geriatric syndrome characterized by a deterioration in muscle mass (sidenote: Martin FC, Ranhoff AH. Frailty and Sarcopenia. 2020 Aug 21. In: Falaschi P, Marsh D, editors. Orthogeriatrics: The Management of Older Patients with Fragility Fractures [Internet]. Cham (CH): Springer; 2021. Chapter 4 ) . Sarcopenia develops as a result of multiple pathophysiologic mechanisms, including inadequate nutrition and physical activity, inflammation, immunosenescence, anabolic resistance, and oxidative stress. The gut microbiota has a significant influence on these processes, particularly those related to inflammation and the immune system. A number of studies have described alterations in the gut microbiota in the elderly, but this is the first study of its kind to explore the role of the gut-muscle axis in sarcopenia.

Sarcopenia: reduced gut diversity...

The gut microbiota of three groups was analyzed via 16S rRNA gene sequencing: 60 healthy controls (average age 68.38 ± 5.79 years), 11 sarcopenic patients with impaired muscle function and reduced muscle mass (average age 76.45 ± 8.58 years), and 16 potentially sarcopenic patients suffering from impaired muscle function only (average age 74.00 ± 6.94 years). Alpha diversity (Chao1 and observed species diversity indices) was found to be significantly reduced in the sarcopenic and potentially sarcopenic subjects compared to the controls. These patients showed a reduction in certain butyrate-producing species (Lachnospira, Fusicantenibacter, Roseburia, Eubacterium and Lachnoclostridium). Butyrate is an essential compound through which the gut microbiota influences host physiology. It is known to reduce inflammation and some studies have shown that short-chain fatty acids (such as butyrate) contribute to the maintenance of skeletal muscle mass. In addition, the genus Lactobacillus was more abundant in the symptomatic individuals than in the controls, with the family Lactobacillaceae identified as a biomarker for the potentially sarcopenic group. At the same time, the family Porphyromonadaceae appears to be a biomarker for sarcopenia.

...and modified functional pathways

To study the functional impact of gut microbiota composition in the patients, the researchers identified a number of altered functional pathways. In the sarcopenic and potentially sarcopenic subjects, some were overrepresented (particularly lipopolysaccharide, or LPS, biosynthesis), while others were underrepresented (phenylalanine, tyrosine and tryptophan biosynthesis pathways, among others). These results suggest that key metabolic pathways related to cellular energy production, protein processing and nutrient transport are differentially regulated in the pathologic setting of sarcopenia. In addition, the enrichment of LPS biosynthesis suggests that sarcopenia is associated with a pro-inflammatory metagenome. These results confirm those of previous studies (sidenote: Volpi, E., Kobayashi, H., Sheffield-Moore, et al. Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am. J. Clin. Nutr. 78, 250–258. https ://doi.org/10.1093/ajcn/78.2.250 (2003) )  showing the importance of phenylalanine, tyrosine and tryptophan biosynthesis pathways in stimulating muscle anabolism in the elderly.

These preliminary results indicate that structural and functional alterations in the gut microbiota may contribute to the loss of skeletal muscle mass and function in sarcopenic patients. However, future studies involving larger samples are needed to confirm this hypothesis.