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You may have already heard about leaky gut syndrome (increased intestinal permeability)—damage to the intestinal lining that creates holes through which travel toxins, bacteria, and large food particles from the digestive tract—all of which are not meant to cross the intestinal lining and can trigger an inflammatory immune response that enters systemic circulation and can manifest disease processes in virtually any area of the body. Leaky gut syndrome is a major contributor to systemic inflammation throughout the body, and is often triggered by an imbalance of bacteria in the gut.

While this condition is relatively well known, a lesser known condition—leaky brain syndrome—was recently investigated by researchers from Sweden. Quite interestingly, they looked at the connection between gut bacteria and a leaky blood-brain barrier (BBB). (They did not call the condition “leaky brain syndrome,” but that’s what it is.) The study was published in the journal Science Translational Medicine.1

Using an animal model, the researchers compared the permeability (leakiness) of the BBB in offspring born to two sets of mice: one set was germ-free, or lacking normal gut bacteria, and the other set had a normal, pathogen-free, gut bacterial population. As it turns out, the germ-free mice were more likely to have offspring that developed a leaky BBB when compared to the mice with a normal bacteria population.

The researchers found that the germ-free mice exhibited decreased expression of tight junction proteins occludin and claudin-5. These tight junction proteins are found between the cells that line the blood-brain barrier (and the intestinal lining). They help hold the BBB together and prevent leaking. This finding explains the increased permeability of the BBB in these mice. In addition, they postulate that it is likely that changes in the gut microbiomte later in life could also negatively affect BBB integrity:

“These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology,” noted Sven Pettersson, MD, PhD, lead researcher. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome.”

The researchers were able to reverse the leaky brain syndrome in germ-free mice when they transplanted beneficial bacteria into the mice’s digestive tracts. By implanting bacteria known to produce the short chain fatty acids (SCFAs) butyrate, propionate, and acetate, which help to repair the leaky BBB (and a leaky gut, for that matter), they were able to reverse the leaky brain syndrome in these mice. In fact, just giving the animals either intravenous or intraperitoneal sodium butyrate stopped the BBB leak, suggesting that the SCFAs may be a mechanism of repair.

The blood brain barrier progressively matures during in utero development and early postnatal stages. The researchers suggest that changes in human maternal gut microbiota between the first and third trimesters2 might trigger increased nutritional demands in late pregnancy that can lead to increased BBB permeability.

Just as the gut microbiota help to regulate a leaky gut, this study implies that they might also regulate the integrity of the blood-brain barrier. The study supports a high-fiber, plant-based diet with cultured foods and pre- and probiotics to help cultivate a healthy population of beneficial SCFA-producing gut bacteria in pregnant and breastfeeding women. This will promote a healthy GI tract and normal development and maintenance of the BBB.

References

  1. Braniste V, Al-Asmakh M, Kowal C, et al., “The gut microbiota influences blood-brain barrier permeability in mice.” Sci Transl Med. 19 Nov 2014;6(263):263ra158.
  2. Koren O, Goodrich JK, Cullender TC, “Host remodeling of the gut microbiome and metabolic changes during pregnancy.” Cell. 2012 Aug 3;150(3):470-80.