Lacticaseibacillus paracasei LC86 mitigates age-related muscle wasting and cognitive impairment in SAMP8 mice through gut microbiota modulation and the regulation of serum inflammatory factors

Abstract

Purpose: Chronic inflammation contributes to the decline in muscle strength and cognitive abilities associated with aging. This study aims to clarify the effects of oral administration of Lacticaseibacillus paracasei LC86 on these age-related declines, as well as its impact on the composition of gut microbiota.

Methods: Senescence-accelerated mouse prone 8 (SAMP8) mice received a 12 week regimen of LC86 (1 × 10⁹ CFU/day). Muscle strength was assessed through forelimb grip strength and four-limb hanging tests. Cognitive function was evaluated through behavioral performance tests, and changes in gut microbiota were analyzed.

Results: Administration of LC86 significantly enhanced muscle strength, demonstrated by increased grip strength and higher glycogen content in the gastrocnemius muscle (p = 0.041, p = 0.017, and p = 0.000, respectively). Behavioral tests suggested that LC86 mitigated age-related cognitive decline. Furthermore, there was a significant decrease in serum pro-inflammatory cytokines, such as IL-6, TNF-α, and MCP-1 (p = 0.002, p = 0.000, and p = 0.005, respectively), and an elevation in the anti-inflammatory cytokine IL-10 level (p = 0.000). An increase in hepatic antioxidant capacity was observed. Significant changes in the gut microbiota composition were noted, including increased populations of Bifidobacterium and Lactobacillus and decreased levels of Escherichia/Shigella and Bacteroides.

Conclusion: The findings suggest that LC86 supplementation mitigates muscle weakness and cognitive impairment in aging SAMP8 mice, potentially through the modulation of inflammation and gut microbiota composition. LC86 emerges as a promising candidate for ameliorating the decline of muscular and cognitive functions associated with aging.

Keywords: Lacticaseibacillus paracasei LC86; cognitive impairment; gut microbiota; inflammatory factors regulation; muscle wasting.

Figure 1

Experimental design, change in body weight of SAMP8 mice, and senescence score. The experimental intervention period was 12 weeks using Lacticaseibacillus paracasei LC86 (A); body weight was measured from week 1 to week 12 (B); senescence score (C) was measured before and at the end of the experiment.

Figure 2

Lacticaseibacillus paracasei LC86 improved muscle strength in SAMP8 mice. Effect of LC86 on forelimb grip strength (A), limb catching ability (B), and muscle glycogen content (C) in gastrocnemius muscle of SAMP8 mice. The correlation between the glycogen level in the gastrocnemius muscle and the forelimb grasping force (D) and the ability to catch the limbs (E) was analyzed in the mice.

Figure 3

Lacticaseibacillus paracasei LC86 improved the cognitive performance of SAMP8 mice. In open-field experiments, LC86 improved the mice’s locomotor distance (A) and dwell time in the central region (B). LC86 decreased the delay in reaching the platform in the water maze experiment in mice (C). LC86 significantly increased dopamine (D) and serotonin (E) levels in mouse hippocampus and dopamine (F) and serotonin (G) levels in striatum.

Figure 4

Lacticaseibacillus paracasei LC86 improved serum inflammatory response and increased liver antioxidant capacity in SAMP8 mice. Effect of LC86 on serum tumor necrosis factor α (A), interleukin 6 (B), monocyte chemoattractant protein-1 (C), and interleukin 10 (D). Effect of LC86 on liver peroxidase activity (E), glutathione level (F), contact enzyme activity (G), and malondialdehyde level (H). Dihydroethidine staining was performed to investigate the effect of LC86 on reactive oxygen species in the liver (I).

Figure 5

Impact of Lacticaseibacillus paracasei LC86 on Gut Microbial Diversity and Composition. The effect of LC86 on the alpha diversity of the gut microbiota was assessed by Chao1 index (A) and Shannon index (B), and its beta diversity (C), examined by principal coordinates analysis (PCoA). Additionally, differential species abundance across groups is characterized using Linear discriminant analysis Effect Size (LEfSe) and Statistical Analysis of Metagenomic Profiles (STAMP) (D,E).

Figure 6

The association of specific microbial species with relevant metadata. TNF α, tumor necrosis factor α; IL6, interleukin 6; IL10, interleukin 10; MCP-1, monocyte chemoattractant protein-1; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; MDA, malondialdehyde; DA, dopamine, HT, serotonin (5-HT).

Figure 7

Hypothetical mechanisms by which Lacticaseibacillus paracasei LC86 ameliorates age-related muscle wasting and cognitive impairment. TNF α, tumor necrosis factor α; IL6, interleukin 6; MCP-1, monocyte chemoattractant protein-1; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; ROS, reactive oxygen species.