scholarly journals Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia

2021 ◽  
Vol 8 ◽  
Author(s):  
Elena de Marco Castro ◽  
Caoileann H. Murphy ◽  
Helen M. Roche

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.

2021 ◽  
Vol 12 ◽  
Author(s):  
Konstantinos Prokopidis ◽  
Edward Chambers ◽  
Mary Ni Lochlainn ◽  
Oliver C. Witard

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover, in vivo and in vitro studies demonstrate the action of specific gut bacteria (Lactobacillus and Bifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut microbiota phenotypes on amino acid utilization and the postprandial stimulation of muscle protein synthesis in older adults.


2019 ◽  
Vol 317 (6) ◽  
pp. C1061-C1078 ◽  
Author(s):  
Nathan Hodson ◽  
Daniel W. D. West ◽  
Andrew Philp ◽  
Nicholas A. Burd ◽  
Daniel R. Moore

Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status; therefore, much research has focused on understanding the molecular mechanisms that underpin this cellular process. Furthermore, older individuals display an attenuated MPS response to anabolic stimuli, termed anabolic resistance, which has a negative impact on muscle mass and function, as well as quality of life. Therefore, an understanding of which, if any, molecular mechanisms contribute to anabolic resistance of MPS is of vital importance in formulation of therapeutic interventions for such populations. This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. This review also summarizes evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance and provides recommendations for future avenues of research that can expand our knowledge of this area.


Author(s):  
Mary Ni Lochlainn ◽  
Ruth C. E. Bowyer ◽  
Claire J. Steves

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.


Author(s):  
Yan Zhao ◽  
Jason Cholewa ◽  
Huayu Shang ◽  
Yueqin Yang ◽  
Xiaomin Ding ◽  
...  

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.


2001 ◽  
Vol 281 (1) ◽  
pp. R133-R139 ◽  
Author(s):  
S. E. Samuels ◽  
A. L. Knowles ◽  
T. Tilignac ◽  
E. Debiton ◽  
J. C. Madelmont ◽  
...  

The influence of cancer cachexia and chemotherapy and subsequent recovery of skeletal muscle protein mass and turnover was investigated in mice. Cancer cachexia was induced using colon 26 adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12CIN3O4S). Reduced food intake was not a factor in these studies. Three days after cachexia began, healthy and tumor-bearing mice were given a single intraperitoneal injection of cystemustine (20 mg/kg). Skeletal muscle mass in tumor-bearing mice was 41% lower ( P < 0.05) than in healthy mice 2 wk after cachexia began. Skeletal muscle wasting was mediated initially by decreased protein synthesis (−38%; P < 0.05) and increased degradation (+131%; P < 0.05); later wasting resulted solely from decreased synthesis (∼−54 to −69%; P < 0.05). Acute cytotoxicity of chemotherapy did not appear to have an important effect on skeletal muscle protein metabolism in either healthy or tumor-bearing mice. Recovery began 2 days after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (−80%; P < 0.05) and later by increased protein synthesis (+46 to +73%; P < 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to protein synthesis and degradation.


2014 ◽  
Vol 39 (9) ◽  
pp. 987-997 ◽  
Author(s):  
Daniel R. Moore ◽  
Donny M. Camera ◽  
Jose L. Areta ◽  
John A. Hawley

Recovery from the demands of daily training is an essential element of a scientifically based periodized program whose twin goals are to maximize training adaptation and enhance performance. Prolonged endurance training sessions induce substantial metabolic perturbations in skeletal muscle, including the depletion of endogenous fuels and damage/disruption to muscle and body proteins. Therefore, increasing nutrient availability (i.e., carbohydrate and protein) in the post-training recovery period is important to replenish substrate stores and facilitate repair and remodelling of skeletal muscle. It is well accepted that protein ingestion following resistance-based exercise increases rates of skeletal muscle protein synthesis and potentiates gains in muscle mass and strength. To date, however, little attention has focused on the ability of dietary protein to enhance skeletal muscle remodelling and stimulate adaptations that promote an endurance phenotype. The purpose of this review is to critically discuss the results of recent studies that have examined the role of dietary protein for the endurance athlete. Our primary aim is to consider the results from contemporary investigations that have advanced our knowledge of how the manipulation of dietary protein (i.e., amount, type, and timing of ingestion) can facilitate muscle remodelling by promoting muscle protein synthesis. We focus on the role of protein in facilitating optimal recovery from, and promoting adaptations to strenuous endurance-based training.


2009 ◽  
Vol 106 (6) ◽  
pp. 2040-2048 ◽  
Author(s):  
René Koopman ◽  
Luc J. C. van Loon

Aging is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk of developing chronic metabolic disease. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of skeletal muscle protein turnover, resulting in an imbalance between muscle protein synthesis and degradation. As basal (fasting) muscle protein synthesis rates do not seem to differ substantially between the young and elderly, many research groups have started to focus on the muscle protein synthetic response to the main anabolic stimuli, i.e., food intake and physical activity. Recent studies suggest that the muscle protein synthetic response to food intake is blunted in the elderly. The latter is now believed to represent a key factor responsible for the age-related decline in skeletal muscle mass. Physical activity and/or exercise stimulate postexercise muscle protein accretion in both the young and elderly. However, the latter largely depends on the timed administration of amino acids and/or protein before, during, and/or after exercise. Prolonged resistance type exercise training represents an effective therapeutic strategy to augment skeletal muscle mass and improve functional performance in the elderly. The latter shows that the ability of the muscle protein synthetic machinery to respond to anabolic stimuli is preserved up to very old age. Research is warranted to elucidate the interaction between nutrition, exercise, and the skeletal muscle adaptive response. The latter is needed to define more effective strategies that will maximize the therapeutic benefits of lifestyle intervention in the elderly.


2021 ◽  
Vol 11 (3) ◽  
pp. 14-23
Author(s):  
Carina Sousa Santos ◽  
Eudes Souza Oliveira Júnior ◽  
Marcus James Lopes de Sá ◽  
Elizabethe Adriana Esteves

Proper maintenance of skeletal muscle mass is essential to prevent sarcopenia and ensure health and quality of life as aging progress. The two determinants of muscle protein synthesis are the increased load on skeletal muscle through resistance exercise and protein intake. For an effective result of maintaining or increasing muscle mass, it is relevant to consider the quantitative and adequate intake of protein, and the dietary source of protein since the plant-based protein has differences in comparison to animals that limit its anabolic capacity. Given the increase in vegetarianism and the elderly population, which consumes fewer food sources of animal protein, the importance of understanding how protein of plant-based protein can sustain muscle protein synthesis in the long term when associated with resistance exercise is justified, as well as the possibilities of dietary adequacy in the face of this demand.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
Eunice T. Olaniyan ◽  
Fiona O’Halloran ◽  
Aoife L. McCarthy

Abstract Amino acid bioavailability is critical for muscle protein synthesis (MPS) and preservation of skeletal muscle mass (SMM). Ageing is associated with reduced responsiveness of MPS to essential amino acids (EAA). Further, the older adult population experiences anabolic resistance, leading to increased frailty, functional decline and depleted muscle mass preservation, which facilitates the need for increased protein intake to increase their SMM. This review focuses on the role of proteins in muscle mass preservation and examines the contribution of EAA and protein intake patterns to MPS. Leucine is the most widely studied amino acid for its role as a potent stimulator of MPS, though due to inadequate data little is yet known about the role of other EAA. Reaching a conclusion on the best pattern of protein intake has proven difficult due to conflicting studies. A mixture of animal and plant proteins can contribute to increased MPS and potentially attenuate muscle wasting conditions; however, there is limited research on the biological impact of protein blends in older adults. While there is some evidence to suggest that liquid protein foods with higher than the RDA of protein may be the best strategy for achieving high MPS rates in older adults, clinical trials are warranted to confirm an association between food form and SMM preservation. Further research is warranted before adequate recommendations and strategies for optimising SMM in the elderly population can be proposed.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1596 ◽  
Author(s):  
Insaf Berrazaga ◽  
Jérôme Salles ◽  
Karima Laleg ◽  
Christelle Guillet ◽  
Véronique Patrac ◽  
...  

The mechanisms that are responsible for sarcopenia are numerous, but the altered muscle protein anabolic response to food intake that appears with advancing age plays an important role. Dietary protein quality needs to be optimized to counter this phenomenon. Blending different plant proteins is expected to compensate for the lower anabolic capacity of plant-based when compared to animal-based protein sources. The objective of this work was to evaluate the nutritional value of pasta products that were made from a mix of wheat semolina and faba bean, lentil, or split pea flour, and to assess their effect on protein metabolism as compared to dietary milk proteins in old rats. Forty-three old rats have consumed for six weeks isoproteic and isocaloric diets containing wheat pasta enriched with 62% to 79% legume protein (depending on the type) or milk proteins, i.e., casein or soluble milk proteins (SMP). The protein digestibility of casein and SMP was 5% to 14% higher than legume-enriched pasta. The net protein utilization and skeletal muscle protein synthesis rate were equivalent either in rats fed legume-enriched pasta diets or those fed casein diet, but lower than in rats fed SMP diet. After legume-enriched pasta intake, muscle mass, and protein accretion were in the same range as in the casein and SMP groups. Mixed wheat-legume pasta could be a nutritional strategy for enhancing the protein content and improving the protein quality, i.e., amino acid profile, of this staple food that is more adequate for maintaining muscle mass, especially for older individuals.


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