There is increasing evidence, especially in animal models, that the diversity and composition of the intestinal microbiota (the set of microorganisms that live in our intestines) can influence brain activity and behavior in some way. Now two studies have just come to light that confirm that the diversity of the intestinal microbiota is somehow involved in mood disorders.
This is good news considering that depression is one of the most common mental disorders in the world. It has been suggested that between 11-15% of the world population may have suffered from depression at some point in their lives. 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 are limited.
Until now, suspicions that the microbiota and depression could 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 were studies that showed that the 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 treatments with antibiotics or genetically modified. In addition, studies in humans were scarce and with a very small number of samples, unrepresentative. Well-controlled clinical trials and robust, repeatable results were lacking.
Things began to change when, at the beginning of 2019, a macro-study with more than a thousand patients was published in which the composition of the intestinal microbiota was correlated with quality of life and depression. The researchers found that the bacteria Faecalibacterium y Coprococcus, butyrate producers, were consistently associated with indicators of good quality of life. On the other hand, bacteria Dialister y Coprococcus they were decreased in people with depression.
Now a couple of works have just been published in Nature Communications confirming the relationship between the diversity and composition of the 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 was observed in genders Eggerthella, Sellimonas, Lachnoclostridium y Don’t tell me in people with acute depressive symptoms. On the contrary, a significant decrease was found in relation to depression in the genders Subdoligranulum, Coprococcus, Eubacterium ventriosum and the families Ruminococcaceae y Lachnospiraceae.
It is known that both the composition of the gut microbiota and the degree of depression vary substantially between different ethnic groups. For this reason, in a second parallel study to the previous one, the intestinal microbiota and its relationship with depressive symptoms were characterized 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 people. The results confirmed those obtained in the previous work, and showed that the intestinal microbiota linked to depressive symptoms was independent of the 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 an antidepressant. Serotonin may be the key neurotransmitter of the gut-brain axis and GABA is the main inhibitory neurotransmitter in the central nervous system that counteracts the action of glutamate.
Low GABA levels are linked to depression and mood disorders. Animal studies 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 brain chemistry and therefore influence mood and behaviour.
However, it must be taken into account that these studies are based on DNA sequencing data from the feces to determine the composition of the bacteria, and that from this data the function that these bacteria could have is inferred.
What is the first chicken or the egg?
All these studies also do not resolve the great question of whether the change in the composition and diversity of the intestinal microbiota is the cause of depression or if, on the contrary, it is the disease that causes a change in the microbiota. In addition, it must be taken into account that these works 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 have 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 grow them in the laboratory on a large scale to prepare probiotics, for example.
In short, we are still a long way from possible treatments for depression based on microbiota interventions. However, these new studies offer strong results in more than 5,000 samples of the link between the composition of the gut microbiota and depression beyond the cultural, genetic and lifestyle differences of different ethnic groups.
A version of this article was originally published on the author’s blog, microBIO.
Ignacio López-Goñi, Member of the SEM (Spanish Society of Microbiology) and Professor of Microbiology, university of Navarra
This article was originally published on The Conversation. Read the original.
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