Probiotic supplementation attenuates age‐related sarcopenia via the gut–muscle axis in SAMP8 mice

Abstract

Background Age-related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut-muscle axis. However, the effects and mechanisms of probiotics in age-related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. Methods We administered LcS (1 × 10 8 or 1 × 10 9 CFU/mouse/day) by oral gavage to senescence-accelerated mouse prone-8 mice for 12 weeks (16-to 28-week-old). Sixteen-week-old and 28-week-old SMAP8 mice were included as non-aged and aged controls, respectively. Muscle condition was evaluated using dual-energy X-ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Gas chromatography-mass spectrometry was utilized to measure the short-chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. ResultsThe LcS supplementation reduced age-related declines in muscle mass (>94.6%, P < 0.04), strength (>66% in holding impulse and >96.3% in grip strength, P < 0.05), and mitochondrial function (P < 0.05). The concentration of short-chain fatty acids (acetic, isobutyric, butyric, penic, and hexanoic acid) was recovered by LcS (>65.9% in the mice given high dose of LcS, P < 0.05) in the aged mice, and LcS attenuated age-related increases in inflammation (P < 0.05) and reactive oxygen species (>89.4%, P < 0.001). The high dose of LcS supplementation was also associated with distinct microbiota composition as indicated by the separation of groups in the beta-diversity analysis (P = 0.027). LcS supplementation altered predicted bacterial functions based on the gut microbiota. Apoptosis (P = 0.026), p53 signalling (P = 0.017), and non-homologous end-joining (P = 0.031) were significantly reduced, whereas DNA repair and recombination proteins (P = 0.043), RNA polymerase (P = 0.008), and aminoacyl-tRNA biosynthesis (P = 0.003) were increased. Finally, the genera enriched by high-dose LcS [linear discriminant analysis (LDA) score > 2.0] were positively correlated with healthy muscle and physiological condition (P < 0.05), while the genera enriched in aged control mice (LDA score > 2.0) were negatively associated with healthy muscle and physiological condition (P < 0.05). Conclusions Lactobacillus casei Shirota represents an active modulator that regulates the onset and progression of age-related muscle impairment potentially via the gut-muscle axis.

Plant-based polyphenol rich protein supplementation attenuated skeletal muscle loss and lowered the LDL level via gut microbiota remodeling in Taiwan's community-dwelling elderly

“…The analysis was performed following the description of a previous study. 15 Differences in abundance were examined by the MetaStat method with adjustments for multiple comparisons.…”

“…Moreover, the gut microbiota was reported to employ SCFAs to benefit the host through several signaling pathways associated with the gut–brain 14 and gut–muscle axes. 15…”

Gut-muscle crosstalk. A perspective on influence of microbes on muscle function

“…It also reduced age related increases in inflammation by down regulating the proinflammatory cytokine TNF- α and upregulating the anti-inflammatory cytokine IL-10. In contrast to the fall in SCFAs usually seen in aging, Lactobacillus casei Shirota helped to maintain the butyrate levels in the aged mice ( 61 ). This study involved a small case series of six non-agenarian older adults (mean age: 90.8 ± 5.4 years) with sarcopenia who were administered the prebiotic 1-kestose (10 g/day for 2 weeks), there was an increase in the intestinal Bifidobacterium longum population along with increased skeletal muscle mass index and reduced body fat percentage ( 62 ).…”

The Effect of Metabolites on Mitochondrial Functions in the Pathogenesis of Skeletal Muscle Aging

“…131 Chen et al showed that the Lactobacillus casei supplementation in elderly mice could produce anti-ROS and anti-inflammatory effects as well as maintain muscle and mitochondrial functions. 132 The mechanism of intestinal microbiota on mitochondria is shown in Figure 1. Although the underlying mechanism needs to be studied further, the existing research evidence shows that the metabolites of intestinal microbiota, especially short-chain fatty acids (SCFA), are key intermediates affecting the gut-muscle axis.…”

“…138 FFAR3 is mainly expressed in adipose tissue and is related to obesity and other metabolic diseases. 132 GPR41 and GPR43, the main receptors of acetate, are expressed in almost all metabolically active tissues of the human body. Therefore, acetate may be one of the most important metabolites of the interaction between intestinal microbiota and host metabolites.…”