There is growing evidence, especially in animal models, that the diversity and composition of the gut microbiota (the set of microorganisms that live in our gut) may somehow influence brain activity and behavior. Now two programs of study have just come to light that confirm that gut microbiota diversity is somehow involved in mood disorders.

This is good news considering that depression is one of the most common mental disorders worldwide. It has been suggested that 11-15 % of the world's population may have suffered from depression. at some point during their lifetime. In many countries it has even increased recently as a side effect of the covid-19 pandemic. However, the cause of depression remains partly unknown, its diagnosis is complicated and treatment options limited.

Until now, suspicions that microbiota and depression may be related were based on experiments in which the transfer of intestinal microbiota from depressed human patients to germ-free rats induced depressive behaviors in the recipient animals. On the other hand, there was programs of study showing that consumption of prebiotics and probiotics could affect mood and anxiety in humans.

However, most of the experiments were based on experimental animals, free of germs or under antibiotic or genetically modified treatments. In addition, the programs of study in humans were few and with a very small issue of samples, unrepresentative. There was a lack of well-controlled clinical trials, robust and repeated results.

Confirmation final
The tables began to turn when, in early 2019, a macro-study of more than 1,000 patients was published correlating gut microbiota composition with quality of life and depression. The researchers found that butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with indicators of good quality of life. On the other hand, Dialister and Coprococcus bacteria were decreased in people with depression.

Now a pair of papers have just been published in Nature Communications confirming the relationship between the diversity and composition of fecal microbiota with depressive symptoms. In the first work they have analyzed samples from 2,593 participants and have identified the association of up to thirteen different microbial groups with depressive symptoms. Above all, a significant increase of the genera Eggerthella, Sellimonas, Lachnoclostridium and Hungatella was observed in people with acute depressive symptoms. In contrast, a significant decrease in relation to depression was found in the genera Subdoligranulum, Coprocococcus, Eubacterium ventriosum and the families Ruminococcoccaceae and Lachnospiraceae.

It is known that both the composition of the gut microbiota and the Degree of depression vary substantially among different ethnic groups. Therefore, a second parallel study characterized the gut microbiota and its relationship with depressive symptoms in six ethnic groups (Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan) from the same urban area (the city of Amsterdam), in a total of 3,021 persons. The results confirmed those obtained in the previous work , and showed that the gut microbiota linked to depressive symptoms was independent of ethnic group .

What does the gut microbiota have to do with depression?
Although the underlying biological mechanisms have not yet been sufficiently studied, it is known that many of these bacteria are involved in the synthesis of glutamate, butyrate, serotonin and gamma aminobutyric acid (GABA), which are key neurotransmitters in depression.

Glutamate is an excitatory neurotransmitter and butyrate has been shown to be antidepressant. Serotonin may be the neurotransmitter core topic of the gut-brain axis and GABA is the main inhibitory neurotransmitter of the central nervous system that counteracts the action of glutamate.

Low GABA levels are associated with depression and mood disorders. The programs of study in animals show that the gut microbiota can alter the activity of these neurotransmitters in the brain via the vagus nerve. Perhaps the production of neurotransmitters by the gut microbiota can alter the brain Chemistry and thus influence mood and behavior.

However, it should be noted that these programs of study are based on data sequencing of stool DNA to know the composition of the bacteria, and from that data the function that these bacteria might have is inferred.

Which comes first, the chicken or the egg?
All these programs of study do not solve the great unknown of whether the change in the composition and diversity of the intestinal microbiota is the cause of depression or whether, on the contrary, it is the disease that causes a change in the microbiota. Moreover, it should be borne in mind that these studies only analyze the bacterial composition of the microbiota and do not take into account the role that other groups of microorganisms (viruses, archaea, fungi and protozoa), which also live in the intestine, may play in our physiology.

On the other hand, many of the bacteria that are related to depression are detected by sequencing methods, but at the moment we are not able to culture them on the laboratory on a large scale to prepare probiotics, for example.

At final, we are still a long way from possible treatments for depression based on microbiota interventions. Nevertheless, these new papers provide compelling results in more than 5000 samples of the link between gut microbiota composition and depression beyond cultural, genetic and lifestyle differences in different ethnic groups.

This article was originally published in The Conversation. Read the original.