Review: Unravelling the link between gut microbiota and skeletal muscle in older age
The authors of the narrative review note that, in older individuals, the gut microbiota is frequently characterised by dysbiosis, overrepresentation of opportunistic pathogens, and increased inter-individual variability.
It is suggested that this may contribute to increasing the variability of biological actions of phenolic compounds at the skeletal muscle level.
The authors conclude: “Phenolic compounds with putative beneficial actions against age-related sarcopenia exhibit a substantial interaction with gut microbial communities that modifies their bioavailability and bioactivity.
“This effect may be particularly emphasised in older individuals who frequently exhibit an age-related dysbiosis of gut microbiota and increased inter-individual variability of bacterial community structure and functions.”
The review highlights the need for further research to advance understanding of this relationship and to develop targeted interventions for preserving muscle health in older individuals.
Sarcopenia and the gut microbiota
Sarcopenia, a prevalent geriatric syndrome characterised by the loss of muscle mass and function in older individuals, poses significant risks such as disability, institutionalisation, and mortality.
The condition often overlaps with frailty and multimorbidity, with various factors contributing to its development, including malnutrition, insulin resistance, chronic inflammation, myocellular mitochondrial dysfunction, and reduced muscle protein synthesis with enhanced catabolism.
Previous research has explored the role of the gut microbiota, the collection of microorganisms residing in the gut, in influencing these mechanisms leading to muscle wasting.
Age-related changes in the gut microbiota composition and function have been linked to the onset of sarcopenia, with an overrepresentation of pathogenic bacteria observed in individuals with the condition.
A key therapeutic approach to combat sarcopenia in older individuals is the promotion of a healthy diet that includes high-quality proteins and plant-based foods rich in polyphenols.
Several previous in vitro and preclinical studies have shown that polyphenolic metabolites have also beneficial effects on skeletal muscle cells, and thus a protective action against muscle wasting.
However, recent studies have contributed to research that gut microbial metabolism is also deeply involved in the biotransformation of dietary polyphenols into bioactive compounds, and the authors of the review hypothesise that the myoprotective action of dietary polyphenols could rely on gut microbiota composition and functionality.
In older age, the intestinal microbiota is characterised by a tendency towards dysbiosis and increased inter-individual variability, yet as the authors note, the impact on the metabolism of dietary bioactives is still poorly investigated.
The comprehensive literature search was conducted using PubMed, using results obtained until March 31, 2023.
Articles focusing on specific phenolic subclasses related to sarcopenia in older individuals were included, and only studies conducted on older human subjects and those explaining the mechanisms between polyphenols, microbiota, and sarcopenia were utilised for discussion.
The authors report that research in animal models and a limited number of human studies have shown that certain polyphenols can have myoprotective effects, enhancing muscle strength and performance.
Previous research also shows that increasing the intake of polyphenols and the administration of polyphenol-based nutritional supplements also have favourable effects on the gut microbiota structure.
However, the authors note that dietary polyphenols undergo extensive transformation by gut microbiota, resulting in a diverse range of bioactive compounds that influence their effectiveness on skeletal muscle.
This variation in response is influenced by the composition and functionality of gut bacteria, especially in older individuals who often have dysbiosis and increased inter-individual variability.
The review found that was particularly true for the oldest patients with a high burden of multimorbidity and polypharmacy, who generally exhibit disruption of gut microbial communities with an overrepresentation of opportunistic pathogens.
The authors note: “A polyphenol-based nutritional intervention that exhibits beneficial effects against physical frailty and sarcopenia in one individual may not be necessarily effective in another individual, due to different interactions with the microbiota.”
They conclude: “A deep knowledge of biochemical pathways involved in gut microbial biotransformation of phenolic compounds could lead to the development of personalised nutritional intervention approaches against physical frailty and sarcopenia.”
The authors note some limitations, as results are “mainly based on the analysis and discussion of evidence not obtained from studies conducted in patients with sarcopenia, but from in vitro investigations, animal studies or from populations of healthy human beings.”
Additionally, the authors state: “The framework of this review was tailored to age-related or chronic disease-related sarcopenia, and did not consider alternative causes of muscle wasting, such as prolonged immobilisation, severe stroke, and primary myopathies such as muscular dystrophy.”
They note that the concepts discussed mainly represent hypotheses that need further investigation and validation.
“Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging”
Authors: Andrea Ticinesi, Antonio Nouvenne, Nicoletta Cerundolo, Alberto Parise, and Tiziana Meschi