Key Takeaways
- The blood-brain barrier can weaken with age. This protective boundary plays an important role in shielding the brain, and increased permeability has been associated with neurological disease.
- Gut metabolites may influence the brain. In preclinical research, TMAO interacted with the blood-brain barrier and helped maintain its integrity following an inflammatory challenge.
- Diet may be part of the gut-brain connection. TMAO is associated with the gut microbiome and is found in high quantities in fish and seafood, giving researchers another avenue to investigate how diet could influence healthy brain aging.
Another Reason Your Diet Matters
Researchers are discovering that compounds linked to the foods we eat and the bacteria living in our gut may directly affect the blood vessels that protect the brain.
In early research, one such compound helped strengthen the blood-brain barrier, calm damaging inflammation, and even improve memory performance in laboratory studies. It's called TMAO.
What is TMAO?
TMAO stands for trimethylamine N-oxide. It’s a small compound connected to both diet and the gut microbiome.
Your body can produce TMAO when gut bacteria break down nutrients such as choline and L-carnitine, found in foods including eggs and red meat. The liver then converts the resulting trimethylamine (TMA) into TMAO.
The researchers were interested in TMAO for several reasons.
Precursors to TMAO, such as choline and L-carnitine, have been shown to improve cognitive function, and there’s evidence that patients with Parkinson’s disease have lower circulating TMAO.
A previous study found that gut microbe-derived short-chain fatty acids, formed from bacterial fermentation of dietary fiber, promote blood-brain barrier integrity and protect the brain’s blood vessels. There are many other classes of gut microbe-derived metabolites, of which TMAO is one.
Would that also support the integrity of the blood-brain barrier?
Improves Recognition Memory
After conducting an extensive series of cellular and animal experiments, researchers found TMAO supports the integrity of the blood-brain barrier following an acute inflammatory assault. When TMAO is ingested in food, bacteria in the gut break it down. It’s then transported to the liver and rapidly converted back to TMAO, which then enters the circulation and finds its way to the blood-brain barrier.This was the first demonstration of a direct interaction of a microbe-derived metabolite with the blood-brain barrier.
This food molecule also had protective effects on the brain’s blood vessels, the brain’s astrocytes – cells that help control blood-brain barrier permeability – and microglia, the brain’s immune cells.
In addition, TMAO not only reduced blood-brain barrier permeability in mice but also improved cognition, with rodents exhibiting better memory for previously encountered situations.
Not only does this study demonstrate the value of TMAO, but it also adds to previous findings showing the importance of gut microbes and the metabolites they produce.
Opens Up Exciting Dietary Possibilities
First author and microbiologist at Nottingham Trent University, Professor Lesley Hoyles, explains more about how TMAO, which is found in high quantities in fish and seafood, interacts directly with the blood-brain barrier to keep it intact and protect the brain’s blood vessels. “This work is a big step forward in better understanding how our diet could positively influence cognitive function and healthy aging.
“Microbiota-produced metabolites come from gut bacteria and have numerous effects on our bodies. We have demonstrated that TMAO – a bacterial metabolite associated with the human gut microbiome and found in high quantities in fish and seafood – has a direct and beneficial interaction with the blood-brain barrier and influences cognitive function.
“This opens up a range of new work exploring dietary interventions that connect the gut and brain.”
Lead author Dr. Simon McArthur at Queen Mary University of London added: “We know that damage to the brain’s blood vessels is a feature of many neurological diseases, including stroke and dementia. By identifying the gut bacteria as able to modify brain blood vessel integrity, our findings open up exciting new avenues for protective intervention by manipulating the diet.
“We have long known that eating fish is good for your brain – now we can add the gut bacteria as a fresh aspect to this old adage.”
My Takeaway
The big question I have is what about taking fish oil? Does this help increase TMAO levels?While these researchers didn’t weigh in on the topic, another study found that, yes, it does.
Research in China found that fish oil increased choline circulation levels in blood plasma while raising the concentration of TMAO.
The studies suggest that regularly eating fish and/or consuming fish oil supplements can help you protect your brain and strengthen your memory and cognitive function. The studies also confirm the importance of a healthy gut in the production of TMAO, so keeping your digestive system in healthy balance with a probiotic supplement is important.
Summary
As we age, the blood-brain barrier—the protective boundary that helps keep harmful substances out of the brain—can become more permeable. Researchers investigated whether TMAO, a compound associated with the gut microbiome and found in high amounts in fish and seafood, could influence this important barrier. In cellular and animal experiments, TMAO helped maintain blood-brain barrier integrity following an inflammatory challenge and produced protective effects involving brain blood vessels, astrocytes, and microglia. Mice exposed to TMAO also performed better on a recognition-memory measure. The findings add to growing research examining the gut-brain connection and raise intriguing questions about whether diet could someday be used to help support the aging brain.
Frequently Asked Questions
What is the blood-brain barrier?
The blood-brain barrier is a highly selective boundary between the bloodstream and brain tissue that helps prevent potentially harmful substances from entering the brain.What happens to the blood-brain barrier as we age?
Research suggests blood-brain barrier integrity can decline with aging, potentially allowing substances from the bloodstream greater access to brain tissue.What is TMAO?
TMAO stands for trimethylamine N-oxide. It is associated with the metabolism of nutrients such as choline and L-carnitine and with the activity of gut bacteria. The article notes that TMAO is also found in high quantities in fish and seafood.Can TMAO improve memory?
The research discussed in the article found improved recognition memory in mice, but this does not establish that increasing TMAO will improve memory in humans.What does this research tell us about diet and brain health?
It provides another possible biological link between diet, the gut microbiome, brain blood vessels, and cognitive function. More human research is needed to determine how these findings translate into dietary recommendations.