Short-Chain Fatty Acids Protect the Blood-Brain Barrier


The gut microbiome plays a significant role in human health and disease. For example, changes in the gut microbiome have been associated with diabetes, inflammatory bowel disease, and Parkinson’s disease.


Studies have shown links between the brain and gut microbiome in humans with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, the interactions between the gut microbiome and the brain are poorly understood.


One of the primary ways in which the gut microbiome affects the host is through the gut-brain axis, wherein substances produced by gut bacteria affect brain function by interacting with the nerves in the gut.


An alternative method for gut bacteria to interact with the brain is by substances produced by gut bacteria entering the bloodstream and crossing the barrier that protects the brain (the blood-brain barrier).


In fact, a number of studies have shown that short-chain fatty acids (SCFAs; acetate, butyrate, and propionate), which are made by bacteria fermenting dietary fiber, are key regulators of the gut-brain axis.


Many studies have focused on the health benefits of butyrate, but fewer have analyzed propionate. Now, however, a study pre-published on bioRxiv has sought to understand the role of propionate in the gut-brain axis.


In the study, researchers used a brain endothelial cell model system to analyze the effects of propionate. They found that propionate and butyrate, but not acetate, have beneficial protective effects on the blood-brain barrier by dampening inflammatory and oxidative (damaging) stimuli via the FFAR3 receptor.


While the study relied on a test tube system to uncover the benefits of propionate, the work has interesting implications if validated in humans. For example, inflammation is now known to be a contributing factor to depression. The inflammatory effects propionate seen in this study may account for the protective effects against depression after prebiotic treatment.