I’ve published many studies linking the gut microbiome to certain health conditions. One of the conditions that has shown significant interest is mood disorders, especially major depressive disorder (MDD). Studies that have linked the gut microbiome to major depressive disorder have been small and have been met with skepticism. A recent study from China may give us more insight into the mechanism by which bacteria in the gut might influence brain chemistry. Researchers collected 311 fecal samples from people with MDD (unmedicated) and from healthy controls. Microbiome researchers were looking for a more precise picture of the organisms present versus a genus level within a batch of microorganisms.
Results found 18 specific bacterial species that were more abundant in those with MDD. They also found 3 specific bacteriophages (viruses that infect bacteria), and 50 fecal metabolites that were significantly associated with MDD verses healthy controls. The gut bacterial metabolites that correlated with MDD were molecules that are involved in amino acid metabolism. The most important pathways were related to gamma-aminobutyric acid (GABA), phenylalanine, and tryptophan metabolism. These molecules enter the blood from the gut, affect neurochemistry, and have been implicated in MDD.
Researchers point out that GABA, a neurotransmitter in the brain, is made by gut microbes. Fecal levels of GABA and some of its metabolites were decreased in the MDD patients. GABA related microbial genes were also altered in MDD patients suggesting that microbes modulate GABA levels. It is possible that this may dysregulate the function of GABA in the brain, and could lead to depressive symptoms.
Scientists also hypothesize that an increase in certain phyla called Bacteroides could increase inflammation which has been linked to MDD. Also decreased Blautia bacteria which has been shown to have anti-inflammatory effects could contribute to MDD. Other studies have found that when fecal transplanting the entire microbiota of a person with MDD into a germ-free rat, it causes “depressive-like” behaviors in the rat.
Epidemiological researchers have found that many people with irritable bowel syndrome are also depressed. Also those on the autism spectrum tend to have digestive problems, and people with Parkinson’s disease are prone to constipation. Researchers have also noticed people taking antibiotics are more prone to depression compared to those taking antiviral or antifungal medications that leave gut bacteria unharmed.
So what is the mechanism behind the actually pathway from the gut to the brain? Some substances secreted by the gut microbes may infiltrate blood vessels for a direct ride to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Indirect links might also exist. Gut bacteria is so important to proper immune function and studies show that having the wrong mix of microbes can promote inflammation. Microbial products can influence enteroendocrine cells which reside in the lining of the gut and release hormones and other peptides. Some of these cells regulate digestion and control insulin production. They also release the neurotransmitter serotonin which escapes the gut and travels throughout the body. This is where our gut flora might influence weight gain, sleep and how we respond to stress.
It’s crazy to think how much influence our gut has to our mood. Depressed symptoms can influence our diet behavior which can influence our gut characteristics and composition. On the other hand, our bacteria can produce some special metabolites and have a specific pathway that can influence our brain function. More research needs to be done to determine whether any of these pathways are actually causally related to depression. Nutritional psychiatry is a new emerging field that is so exciting. We may be able to target the microbiome through diet (and specific probiotics) which could alleviate some of the symptoms of depression.
This is one more piece of evidence that shows a strong association of microbiome function and mental wellbeing.
Reference: Yang J et al. Landscapes of bacteria and metabolic signatures and their interactions major depressive disorders. Sci Adv 2020 Dec 2; 6:eaba8555.