Akkermansia muciniphila in Alleviating Cognitive Impairment

The Impact of Insufficient Sleep on Cognitive Function

Adequate sleep is crucial for the brain's normal functioning. In contrast, both voluntary sleep deprivation (SD) and disrupted sleep patterns are increasingly common in modern societies. These conditions detrimentally affect cognitive capabilities, contributing to attention deficits, memory impairments, and decreased cognitive abilities. They can even boost the risk of dementia. Nonetheless, the underlying mechanisms and effective clinical interventions for cognitive impairments induced by SD are still vastly unexplored.

The Role of Gut Microbiota in Cognitive Impairment

Important breakthroughs have been made in the understanding of these mechanisms. Researchers, using SD mouse models, reveal that an imbalance in gut microbiota can trigger an overconsumption of synapses by microglial cells, leading to cognitive impairments. Relative to control mice with normal sleep, SD mice demonstrated significant cognitive impairments. This was evident through their poorer performance in cognitive function tests such as open-field exploration and novel object recognition maze tests. Researchers analyzed the gut microbiota of normal sleep and SD mice using 16S rRNA sequencing and noted significant decreases in the mice's Akkermansia muciniphila abundance after seven days of SD. These results hinted strongly that gut microbiota imbalance worsens the cognitive deficits in SD mice.

Akkermansia muciniphila for SD-Induced Cognitive Impairment

Interestingly, the same researchers found that when SD mice were supplemented with Akkermansia muciniphila, there was a significant increase in the levels of this bacterium in the caecum. Concurrently, these mice demonstrated improved performance in cognitive function tests, and this improvement was associated with a reduced loss of synapses in the mice's dentate gyrus. Seven days of SD significantly increased microglial cell activation in the mice's hippocampus, increasing the expression of complement C1q, a key protein involved in synaptic pruning and swallowing, and CD68, a positive lysosomal marker characterizing microglial cell swallowing activity. However, the levels of these markers declined after supplementing Akkermansia muciniphila eventually inhibiting the activation of microglial cells.

Fig.1 A. muciniphila supplement restores SD-induced cognitive deficits in mice.¹

Remarkably, similar results were obtained when these mice were directly supplemented with acetate and butyrate, indicating that these short-chain fatty acids have a comparable effect to that of Akkermansia muciniphila. There was a reduction in the activation and synaptic swallowing of microglial cells in the hippocampus, resulting in improved performance in cognitive function tests.

Collectively, this research provides substantial evidence linking gut microbiota dysbiosis to cognitive deficits caused by SD, through the activation and synaptic swallowing of microglial cells. From this perspective, supplementing with Akkermansia muciniphila or short-chain fatty acids can counter this process, consequently improving cognitive abilities. As a next-generation probiotic, Akkermansia muciniphila is already being tested in some clinical trials. It leaves room for speculation as to whether supplementing Akkermansia muciniphila or short-chain fatty acids could become an effective strategy for preventing cognitive impairments in sleep disorder patients – a question that deserves further exploration in future research.

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Reference

1. Li, Na, et al. "Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses." Gut Microbes 15.2 (2023): 2252764.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.