Could a Ketogenic Diet Alter the Microbiome to Protect Brain Health?

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Each of our guts is an ecosystem of microorganisms. It’s well-known that we shape this ecosystem by choosing the foods we put into our bodies and that, in turn, this ecosystem affects how our body and brain functions. However, the nuances of this reciprocal relationship remain to be elucidated. 


A study published in the prestigious journal Nature, recently added a piece to this puzzle. The data presented in this study suggest that a low-carb high-fat ketogenic diet can alter gut bacteria in mice to protect against the development of neurological disease! (https://www.nature.com/articles/s41598-018-25190-5)


Diving into the methodology and results, the researchers fed young healthy mice either a low-carb high-fat ketogenic diet or a control diet for 16 weeks. The results they observed were shocking. First, (1) the mice on the ketogenic diet exhibited a marked increase in blood flow and oxygen to the brain. Second, (2) levels of the protein mTOR, the infamous poster child of cellular aging, were decreased by one-third in the brains of the ketogenic mice. Third, (3) the fat-fueled keto-mice demonstrated an astonishing 185% increase in the activity of P-glycoprotein, a transporter that functions to clean the neurotoxin Aβ, which contributes to Alzheimer’s disease, out of the brain. Together, these results are consistent with the idea that a ketogenic diet might protect young healthy brains from developing cognitive decline.


But that’s only the first part of the story.  The really interesting part, in my opinion, is how these effects might be mediated by changes in gut bacteria. When examining the microbial compositions of the keto-mice and control mice, the researchers found that levels of the beneficial bacteria Lactobacillus and Akkermansia were doubled to tripled, whereas the potentially harmful gut bacteria Desulfovibrio and Turicibacter were almost eliminated, in the keto-mice. 


Okay… interesting… but are these changes in gut bacteria related to the beneficial changes in brain metabolism? Well, maybe. It’s been hypothesized that certain brain diseases actually begin in the gut. For example, the gut-brain hypothesis of Parkinson’s disease, the world’s second most common neurological disorder, is growing in popularity among scientists. Furthermore, it has been observed that the presence or absence of certain gut microbes alters cognitive function and is associated with particular neurological diseases. Finally, it is well-documented that ketogenic diets improve the symptoms of conditions such as Alzhiemer, Parkinson’s, and autism, in association with critical changes in patients’ gut bug ecosystems.


Returning to our keto-mice, the particular changes identified in their guts were compelling. Lactobacillus and Akkermansia, levels of which were increased in the keto-mice, are known to produce certain short-chain fatty acids (SCFAs) that can protect the blood-brain barrier, improve cerebral blood flow and, perhaps, increase clearance of the Aβ toxin; these are precisely the changes that were observed in the animals’ brains! Furthermore, Desulfovibrio and Turicibacter, levels of which were decreased in the keto-mice, are associated with risk factors for cognitive decline, such as chronic inflammation and obesity. Again, the keto-mice demonstrated the corresponding adaptations. In fact, the keto-mice weighed less than the control mice, despite eating almost twice as many calories.


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In their own words, the authors of this paper conclude that “these findings imply that dietary intervention started in the early stage may evoke neuroprotective effects via neurovascular and gut microbiome changes.” It’s an exciting idea: by choosing the right foods, we can shape our microbial ecosystems and, in so doing, may protect the health of our most precious organ – the brain! Of course, these results must be replicated and more research needs to be done to clarify how our bugs talk with our brains, but I for one am at the edge of my seat to see where this research takes us! Stay tuned!



Nicholas Norwitz