Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia

Abstract

Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.

Gut Microbial, Inflammatory and Metabolic Signatures in Older People with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study

“…Although our investigation does not provide mechanistic elements to support such a hypothesis, the relevance of systemic inflammation to PF&S has previously been shown [11]. From this perspective, systemic inflammation would represent one of the effectors of the "gut-muscle axis" that has recently been proposed to contribute to the development of PF&S [23,63,67].…”

Heat-Killed Bifidobacterium breve B-3 Enhances Muscle Functions: Possible Involvement of Increases in Muscle Mass and Mitochondrial Biogenesis

“…Recent studies have suggested that Bifidobacterium is recognized as a key taxon for physical frailty and sarcopenia in elderly individuals [8]; however, it remains unclear whether the decreases in bifidobacterial abundance that occur with age influence muscle health [7,41]. The present study explored the positive relationships between Bifidobacterium and muscle health.…”

“…Accumulating evidence has indicated that gut microbiota are associated with host health conditions in numerous ways [4], including through energy metabolism and mitochondrial function [5,6]. Moreover, the cross-talk pathway between the gut microbiota and skeletal muscle, i.e., the gut-muscle axis, has been extensively studied, and microbiota composition and the intestinal environment have been suggested to influence muscle mass and function, possibly by modification of microbiota composition, immune function, energy metabolism and oxidative stress [7,8]. However, studies on the effects of probiotics on muscle mass and function have been scarcely reported, and the potential effects of probiotics on physical performance and their underlying mechanisms remain unclear.…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…However, if several studies in animals indicate the possibility of a gut-muscle axis, it is important to outline that the reverse signaling from the muscle to the gut might also occur. Indeed, microbes develop a symbiontic reaction with their host and, consequently, reduced physical activity in sarcopenic subjects may be associated with different microbiota composition and metabolism [211,212]. This last point might be considered when the physical performance is measured in humans by gait speed test, because gut bacteria synthesize neurotransmitters such as serotonin, norepinephrine, GABA, or dopamine are able to influence the neurological control of movement [213].…”