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Gut Microbiome Is Altered In Persons With Major Depression

It turns out that people experiencing a major depression have differences in their gut microbiome (community of microbes) when compared to healthy people who are not depressed. A persistent and prolonged period of extreme sadness or depression is called a major depressive disorder (MDD).

A team of researchers (in both China and the US) analyzed stool samples from 311 people  with either MDD or healthy and not-depressed (the control group). They used modern genetic sequencing to see what microbes were in the stools. They found differences in 47 bacterial species, 3 bacteriophages (a virus that infects bacteria), and 50 fecal metabolites - which suggested to the researchers that depression is characterized by gut microbiome problems (it's imbalanced or out of whack).

There actually was a "signature composition" of gut microbes in the depressed persons, all of whom were unmedicated. They found higher levels ("increased abundance") of 18 bacterial species in people with MDD (mainly belonging to the genus Bacteroides) and 29 were less common (mainly belonging to Eubacterium and Blautia), when compared to healthy persons.

The researchers point out that other studies also find the gut microbiome to be imbalanced in MDD, and there are animal experiments showing that the gut microbiome has a role in causing MDD (e.g. transplanting gut microbes from a depressed person into a rat results in the rat exhibiting depressive behaviors).

Excerpts from The Scientist: Distinct Microbiome and Metabolites Linked with Depression

The human gut microbiome is a world in miniature, populated by a chatty community of bacteria, viruses, fungi, and protozoa nestled within various gastrointestinal niches. Over the past decade, researchers have linked disturbances within this complicated microbial society to a variety of diseases. Major depressive disorder (MDD) is one such condition, but the studies have been small and the findings imprecise.  

A study published December 2 in Science Advances changes all that with its vivid description of a distinct microbiome associated with major depressive disorder, as well as the profile of molecules these organisms produce. The researchers were able to use this microbial “fingerprint” to distinguish between individuals with MDD and healthy controls, solely on the composition of a few microbes and compounds in their fecal matter.

They found that 18 bacterial species were more abundant in people with MDD (mainly belonging to the genus Bacteroides) and 29 were less common (primarily the genera Blautia and Eubacterium) compared to healthy controls. Hu and his team also found three bacteriophages (viruses that infect bacteria) whose levels were different in MDD versus healthy controls, the first time the virome has been studied in MDD.

Hu’s team then created a biomarker panel consisting of two species of bacteria, two types of bacteriophage viruses, and two different metabolites. In a separate group of 75 subjects (half with MDD, half healthy controls), the biomarker panel was able to accurately pick out those with depression around 90 percent of the time.

The researchers point out that GABA is a neurotransmitter in the brain, but it’s also made by gut microbes; fecal levels of GABA and certain of its metabolites were decreased in the MDD patients, and the team also found that GABA-related microbial genes were altered in MDD patients, suggesting that microbes modulate GABA levels. Hu and his team hypothesize that this may dysregulate the function of GABA in the brain, and could lead to depressive symptoms.

In addition, the scientists hypothesize that perhaps the increase in Bacteroides bacteria, which induce cytokine production, could increase inflammation, a condition that has been linked to MDD. Also, decreased Blautia, which has been shown to have anti-inflammatory effects, could contribute to MDD. Other studies have also found that when researchers transplant the entire microbiota of a person with MDD into a germ-free rat, the rat starts to behave depressed.

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