How Metformin Affects Brain Function and Gut Bacteria

Jenn Hoskins
6th March, 2024

How Metformin Affects Brain Function and Gut Bacteria

Image Source: Natural Science News, 2024

Key Findings

  • In patients with type 2 diabetes, metformin may improve gut health and brain function
  • Metformin use is linked to better cognitive test scores, suggesting it protects brain health
  • The drug could help manage diabetes and potentially fight cognitive decline and dementia
Understanding the complex interactions between our body's systems is critical for tackling age-related cognitive decline, a condition affecting millions globally. Type 2 diabetes (T2D), a chronic condition characterized by high blood sugar levels, has been identified as a risk factor for cognitive impairment and dementia. Intriguingly, a common medication for T2D, metformin, may have a role beyond blood sugar control. Researchers from Dr. Josep Trueta University Hospital have delved into the effects of metformin on the human gut microbiome and cognition, shedding light on the potential bidirectional relationship between these factors[1]. The human gut is home to trillions of microorganisms that influence various aspects of health, including brain function. In T2D patients, the gut microbiome often undergoes dysbiosis, an imbalance that can exacerbate insulin resistance and inflammation. Metformin, while primarily used to improve insulin sensitivity, also appears to positively alter the gut microbiota, potentially reversing dysbiosis. Previous research in mice has established that metformin-induced changes in the gut microbiota can enhance cognitive function, particularly in the context of aging. For example, the presence of a specific gut bacterium, Akkermansia muciniphila, was found to be increased by metformin treatment, leading to reduced inflammation and improved cognitive outcomes in elderly mice[2]. This suggests that metformin's cognitive benefits could be mediated through its effects on gut bacteria. Hypertension, another common condition in the aging population, is known to impair cognitive function by affecting the brain's blood vessels and promoting inflammation. Studies have highlighted the importance of managing blood pressure to prevent cognitive decline[3]. While metformin is not a treatment for hypertension, the shared pathways of inflammation and vascular health link these conditions and highlight the complexity of factors influencing brain health. A methodological approach called Mendelian randomization has provided evidence in support of metformin's protective role against Alzheimer's disease, even in non-diabetic individuals. This approach uses genetic variations as natural experiments to infer causal relationships. The findings suggest that metformin's impact on mitochondrial function could be one mechanism by which it protects against dementia[4]. In the realm of human studies, analyses of older adults have shown associations between glucose metabolism and cognitive performance. Metformin use in diabetic patients was associated with better cognitive test scores, suggesting a protective effect of the drug on brain function[5]. The review by Dr. Josep Trueta University Hospital builds on these findings by focusing on human studies that explore the relationship between metformin use, changes in the gut microbiome, and cognitive function. It is suggested that metformin may not only help in managing T2D but also in restoring gut microbiome balance. This, in turn, could lead to improved cognitive outcomes. The methods used to draw these conclusions involve examining changes in the taxonomy (the classification of organisms) of the gut microbiome, functional changes (how the microbiome operates), and circulating metabolites (substances produced by metabolism) in response to metformin. By looking at these factors, researchers aim to understand how the gut microbiome might influence brain health and whether metformin can positively impact this interaction. In summary, the research from Dr. Josep Trueta University Hospital contributes to a growing body of evidence suggesting that metformin could have unexpected benefits for cognitive health, potentially through its effects on the gut microbiome. This review ties together previous animal and human studies that have hinted at this connection, providing a clearer picture of how managing T2D with metformin could also help in the fight against cognitive decline and dementia. As with all emerging research, more studies are needed to fully understand these relationships and to confirm whether metformin could be part of a strategy to maintain cognitive function into old age.

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References

Main Study

1) Metformin, Cognitive Function, and Changes in the Gut Microbiome.

Published 4th March, 2024

https://doi.org/10.1210/endrev/bnad029

Related Studies

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

https://doi.org/10.1186/s40168-023-01567-1

3) Hypertension, Neurovascular Dysfunction, and Cognitive Impairment.

https://doi.org/10.1161/HYPERTENSIONAHA.122.18085

4) Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study.

https://doi.org/10.1007/s00125-022-05743-0

5) Individual and Combined Associations of Glucose Metabolic Components With Cognitive Function Modified by Obesity.

https://doi.org/10.3389/fendo.2021.769120


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