Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways

Immunity & Ageing

Research

Yun-Ha Hwang¹  Yoon-Jung Shin²  Hee-Seo Park²  Xiaoyang Ma²  Ji-Su Baek²  Dong-Hyun Kim³ 

[1] DongWha Pharm Research Institute, 17084, Yongin-shi, Gyeonggi, Korea;Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, 02447, Seoul, Korea;Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, 02447, Seoul, Korea;PBLbiolab, Seongbuk-gu, 02823, Seoul, Korea;

关键词: Sarcopenia;    Muscle atrophy;    Protein synthesis;    Gut microbiota;    Bifidobacterium bifidum;    Lactobacillus paracasei;   

DOI  :  10.1186/s12979-023-00381-5

 received in 2023-09-02, accepted in 2023-10-10,  发布年份 2023

来源: Springer

【 摘 要 】

Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice. Oral administration of Lp, Bb, or their mix (LB) increased grip strength and treadmill running distance and time. They significantly increased muscle weight in aged mice. They also increased AKT activation, PGC1α, SIRT1, and myosin heavy chain (MyHC) expression, MyHC-positive cell population, and cell size in the gastrocnemius (GA) muscle, while FOXO3a and NF-κB activation, MuRF1, muscle atrophy F-box, and p16 expression, and NF-κB+CD11c+ cell population decreased. Furthermore, they reduced cognitive impairment-like behavior, IL-6 expression, FOXO3a activation, and NF-κB-positive cell population in the hippocampus, GA, and colon, while hippocampal brain-derived neurotropic factor expression increased. They shifted gut microbiota composition in aged mice: they increased Akkermansiaceae and Bacteroidaceae populations, which were positively correlated with total muscle weight and MyHC expression, and decreased Odoribacteraceae and Deferribacteriaceae populations, which were positively correlated with MuRF1 and IL-6 expression. LB alleviated sarcopenia- and cognitive impairment-like symptoms more potently than Lp or Bb alone. Based on these findings, probiotics, particularly Lp, Bb, and LB, can alleviate aging-dependent sarcopenia and cognitive impairment by regulating gut microbiota-mediated AKT, NF-κB, and/or FOXO3a signaling pathways.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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