The Gut-Brain Connection

Our gastrointestinal system is teeming with diverse bacteria that collectively comprise our gut microbiome. These bacteria contribute to our digestive capability as well as more broadly influencing our overall health and wellbeing. As the bacteria in our gut digest our food they produce and excrete their own biomolecules that we call metabolites. Bacterial metabolites can be identical to compounds produced by our own cells. For example, gamma-aminobutyric acid (GABA) is a neurotransmitter produced in our brain that is also produced by some gut bacteria. Alternatively, bacterial metabolites can be unique and novel compounds that our bodies do not produce. Some of these novel bacterial metabolites are inert compounds that do not affect us while others are potent biological mediators that exert significant effects on our cell functions. The effects of bacterial metabolites can be localized to the gut or can act on other organs as the metabolites enter the bloodstream and circulate throughout our bodies. How our gut bacteria and their metabolites contribute to our bodily functions is an active area of investigation.

There is accumulating evidence that the specific composition of a person’s gut microbiome can make a significant contribution to diseases ranging from diabetes to mental health. A recent study in the journal Science Advances compared the microbiomes of individuals with major depressive disorder (MDD) with matched healthy controls. Fecal samples were collected from 236 individuals (half MDD patients and half controls), and all samples were subjected to DNA sequencing to identify bacterial species. Using the sequencing results they defined a “bacterial fingerprint” that distinguished between the MDD patients and the control group. The MDD cohort had 18 bacterial species (mostly from the genus Bacteriodes) that were more prevalent than in the control group and 29 species (mostly of the Blautia and Eubacterium genera) that were less abundant. To extend these results the researchers also evaluated gut metabolite production by both groups and again found significant differences. The MDD group showed a difference in 50 metabolites compared to the control group with 16 metabolites increased and 34 metabolites decreased in the MDD patients. Intriguingly, one of the gut metabolites showing differences between the two groups was the neurotransmitter GABA whose production was significantly reduced in MDD patients. While such observations are still just correlative and do not prove causation, the reduced gut GABA levels could potentially be affecting brain function in ways that contribute to MDD. To establish causality, further studies will need to manipulate bacterial levels in MDD patients to see if clinical symptoms can be improved.

A second important feature of this paper was assessing a diagnostic biomarker panel for MDD. The diagnosis of MDD is currently based on clinical interviews which have a high rate of error. The researchers in this study screened a separate group of 75 subjects (half MDD patients and half controls) for a small subset of the bacteria and metabolites that distinguish MDD patients from controls. By examining this limited panel of markers they correctly predicted nearly 90% of the MDD patients. Even if there is no causal relationship between these markers and MDD, using this quantitative approach to bacterial and metabolite levels may lead to a new diagnostic tool for MDD. Having a  consistent diagnostic tool would be a valuable advance for MDD and would make future studies of the biological basis for major depressive disorder more reliable.

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