Akkermansia muciniphila, which is enriched in the gut microbiota by metformin, improves cognitive function in aged mice by reducing the proinflammatory cytokine interleukin-6

Zhu, Xiaoqi1; Shen, Junyan1; Feng, Shengyu1; Huang, Ce1; Wang, Hao1; Huo, Fengjiao1; Liu, Hailiang1,2,3

2023-05-30

10.1186/s40168-023-01567-1

MICROBIOME   Impact Factor & Quartile

2049-2618

Background Metformin, a type 2 diabetes treatment, improves the cognitive function of aged mice; however, whether the protective effects of metformin on cognitive function in aged mice are associated with the gut microbiome is poorly understood. Although some studies suggest that the gut microbe composition influences cognitive function and that manipulating the gut microbiota might protect against age-related cognitive dysfunction, there is no direct evidence to validate that the gut microbiota mediates the effect of metformin on cognitive improvement.Results In this study, we show that the gut microbiota is altered by metformin, which is necessary for protection against ageing-associated cognitive function declines in aged mice. Mice treated with antibiotics did not exhibit metformin-mediated cognitive function protection. Moreover, treatment with Akkermansia muciniphila, which is enriched by metformin, improved cognitive function in aged mice. Mechanistically, A. muciniphila decreased pro-inflammatory-associated pathways, particularly that of the pro-inflammatory cytokine interleukin (IL)-6, in both the peripheral blood and hippocampal profiles, which was correlated with cognitive function improvement. An IL-6 antibody protected cognitive function, and an IL-6 recombinant protein abolished the protective effect of A. muciniphila on cognitive function in aged mice.Conclusion This study reveals that A. muciniphila, which is mediated in the gut microbiota by metformin, modulates inflammation-related pathways in the host and improves cognitive function in aged mice by reducing the pro-inflammatory cytokine IL-6.

A. muciniphila Metformin Gut microbiota Cognitive function Inflammation IL-6

SCI

English

Corresponding

National Key Research and Development Program of China[2020YFC2002800] ; National Natural Science Foundation of China[82271593] ; Fundamental Research Funds for the Central University[22120210584]

Microbiology

Microbiology

WOS:001000080600001

BMC

Web of Science

1.Tongji Univ, Shanghai East Hosp, Inst Regenerat Med, Sch Med, Shanghai 200123, Peoples R China
2.Shihezi Univ, Coll Life Sci, Key Lab Xinjiang Phytomed Resource & Utilizat, Minist Educ, Shihezi 832003, Peoples R China
3.Southern Univ Sci & Technol, Inst Adv Biotechnol, Shenzhen 518055, Peoples R China

Zhu, Xiaoqi,Shen, Junyan,Feng, Shengyu,et al. Akkermansia muciniphila, which is enriched in the gut microbiota by metformin, improves cognitive function in aged mice by reducing the proinflammatory cytokine interleukin-6[J]. MICROBIOME,2023,11(1).

Zhu, Xiaoqi.,Shen, Junyan.,Feng, Shengyu.,Huang, Ce.,Wang, Hao.,...&Liu, Hailiang.(2023).Akkermansia muciniphila, which is enriched in the gut microbiota by metformin, improves cognitive function in aged mice by reducing the proinflammatory cytokine interleukin-6.MICROBIOME,11(1).

Zhu, Xiaoqi,et al."Akkermansia muciniphila, which is enriched in the gut microbiota by metformin, improves cognitive function in aged mice by reducing the proinflammatory cytokine interleukin-6".MICROBIOME 11.1(2023).