[Health] Guts and Brain

This article was originally submitted for a writing contest held by billionaire Naveen Jain's bio company Viome.

The idiom “you are what you eat” may be based more on reality than you might think. Scientific research is beginning to better understand the connection between bacteria in the digestive system and its impact on the neurological system. Metazoans, such as humans, are significantly affected by gut bacteria (known as microbiota) in critical aspects of our physiology – notably our brain through metabolism and the immune system. The human body contains trillions of microorganisms – outnumbering human cells by 10 to 1 – with many of them being in our gut starting from the esophagus and ending in the colon.

Microbiota regulates the metabolism of humans through generating a concoction of essential vitamins and other nutrients for the host. Upon consuming complex carbohydrates, microbiota metabolize the fiber into short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate. SCFAs produced in our intestines travel not only into our blood serum but these fatty acids can also cross the blood-brain barrier (BBB). One particular SCFA –acetate—affects changes in the hypothalamus, altering physiology, which leads to hormone signals being produced which give a sense of satiety. A small study with humans has shown that consuming such complex carbohydrates leads to feeling full.

Microbiota also has a clear effect on the human immunological system which indirectly affects the human brain. A better-known example is sickness behavior. This behavior is characterized by appetite suppression, decreased motor activity, loss of social interaction, and reduced cognition. Microbial-associated molecular patterns (MAMPs) activate cells of the immune system such as macrophages, neutrophils, and dendritic cells. Once activated, they produce pro-inflammatory cytokines that make their way to the brain by crossing the BBB. In the brain, the cytokines act on neuron receptors, which leads to sickness behavior – in fact studies have shown that one-third of patients can develop major depressive disorder.

Increasingly, microbiota has been shown to directly affect the nervous system – both for good and bad. For instance, psychiatric and neurological illnesses such as schizophrenia, autism, neurodegenerative diseases, and depression are often co-existing with gastrointestinal (GI) pathology. Recent observations have also shown that microbiota alter parts of their hosts’ neurological function, which modify moods and behaviors including depression, anxiety, social behavior, and mate choice, e.g., a subset of autism spectrum disorder (ASD) for children has corresponded with GI complications including constipation, increased intestinal permeability, and altered composition of the gut microbiome.

Probiotic supplements and even just diet have been shown in different lab experiments with mice to affect anxiety, depressive level, learning and memory. A study on humans conducted by Tillisch et al. show that after several weeks of probiotics, there were less reports of sadness and aggressive thoughts. A larger human study of 55 individuals by Messaoudi et al. showed that probiotics can result in decreased anxiety and decreased urinary cortisol. Though mechanisms are not precisely understood, some probiotics are known to lower inflammatory cytokines and decrease oxidative stress which can potentially lead to increased brain-derived neurotrophic factor (BNDF, a protein that is a known cause of depression and anxiety.

The research findings point to practical ways to improve human health. Future therapies for brain disorders such as depression or autism may target specific microbes rather than specific brain disorders. This could be in the form of either ingesting synthetic chemicals mimicking those produced by the “good” bacteria or transplanting the selected bacteria from a healthy donor. The work in this area is still nascent with an example being fecal transplantation investigated for Parkinson’s disease patients.

All studies show that the gut has a significant effect on the brain. However, there is an increasing need to understand the molecular, cellular, and physiological basis of enteric microbiome-gut-brain interaction.