The Mediterranean diet and cognition: is the gut microbiome the key?

Investigations of the Mediterranean diet, the gut microbiome and cognition have revealed intriguing associations between the three…

A recent study from researchers at Tulane University (LA, USA), led by Demetrius Maraganore, has utilized rat models to explore the potential role of the gut microbiome in the relationship between the Mediterranean diet and cognitive performance. The study identified correlations between fluctuations in the gut microbiome and the rat’s ability to execute cognitive tests, providing an insight into potential nutritional regimens that could influence cognitive development.

While benefits of the Mediterranean diet on health and wellbeing have long been extolled, the claims surrounding the exceptional longevity imparted by the Mediterranean diet have taken a hit recently, after Saul Justin Newman (University College London Centre for Longitudinal Studies, UK) was awarded the 2024 Ig Nobel Prize in demography for his work demonstrating that this link can perhaps be better explained by poor record keeping. However, clinical studies have indicated that the diet can improve cognition in 9 to 14-year-olds when compared to a Western diet, through a mechanism that is yet to be understood.

Familiar with the powerful influence of the gut–brain axis, Maraganore and his team set out to investigate how the Mediterranean diet influences the gut microbiome and in turn, how these changes correlated to changes in cognition.

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To do this, fecal DNA was extracted from a cohort of 20 10-week-old male rats, using Zymo Research’s (CA, USA) Quick-DNA™ Fecal/Soil Microbe Microprep Kit and – following library preparation – 16S metagenomic sequencing was conducted using an Illumina (CA, USA) MiSeq sequencer. The rats were then separated into two groups of ten, with one fed a Western and the other a Mediterranean diet for 14 weeks, at which point further metagenomic sequencing of the rats’ gut microbiome was conducted. Both cohorts were then exposed to a series of cognitive tests to complete – a Y-maze, a Morris water maze and a water radial arm maze – that test for memory and learning.

Blood tests were also conducted to investigate cytokine and cholesterol profiles. Meanwhile, qRT-PCR was used to investigate changes in markers for blood–brain barrier permeability at the hippocampus and striatum to establish a possible mechanism for the influence of the gut microbiome on these key regions for memory and learning.

The study revealed that the Mediterranean diet led to an increase in four species of gut bacteria, including Candidatus Saccharimonas – which is associated with positive health benefits – and a decrease in five other species. The performance of the Mediterranean diet group in the cognitive tests was significantly improved compared to the Western diet group, and these changes were also closely correlated to the changes in the microbiome. In particular, the increase in C. Saccharimonas was correlated with better cognitive performance, while increased levels of Bifidobacterium aligned with poorer memory function.

The blood tests revealed that the Mediterranean group maintained lower LDL cholesterol and displayed an increase in both pro- and anti-inflammatory cytokines. However, after correcting for multiple comparisons, pro- to anti-inflammatory cytokine ratios did not differ by diet and the Mediterranean diet was not shown to be inflammatory. The qRT-PCR showed no difference between the two groups in the permeability of the blood–brain barrier.

While the team highlights the need to confirm these results in larger human studies, recognizing the limitations of animal model studies, they are encouraged by their findings. Commenting on the results, Maraganore stated that they indicate “…that the Mediterranean diet or its biological effects could be harnessed to improve scholastic performance in adolescents, or work performance in young adults. While these findings are based on animal models, they echo human studies linking the Mediterranean diet to improved memory and reduced dementia risk.”