Depression, also an intestinal disease?
Major depressive disorder affects 15 to 20% of people of all ages worldwide. Knowledge about this illness is incomplete, but a new area of investigation is the intestinal microbiota.
A widespread debilitating disease
According to the World Health Organization, major depressive disorder, also known as depression, is a common mental disorder. It is characterized by the presence of a depressed mood or a lasting loss of interest or pleasure. This incapacitating psychiatric disorder is the leading cause of disability worldwide and is associated with 800,000 deaths by suicide per year. One out of two patients does not respond sufficiently or not at all to their treatment.
Microbiome, microbiota, what are they?
For the past few decades, there has been interest in our intestines, which are said to be our "second brain." Consequently, researchers are exploring their role in depression and what answers they could provide to this disease by deepening our knowledge of this organ that has long been neglected. The human microbiome consists of microorganisms found throughout the body, particularly in the mouth, intestines, and vagina, as well as on the skin and in the eyes. The microbiota is the collection of microorganisms (bacteria, microfungi, protists) living in a specific environment. For example, the intestinal microbiota is considered necessary and therefore integrated into the host's function, leading some to describe this population as a neglected organ. (See article "Our Second Brain")
The brain-gut microbiota axis, a major axis
The brain-gut axis is a concept that emerged in the 1980s and has since evolved to become the brain-gut microbiota axis. Intestinal microbes located in the brain-gut axis communicate with the brain via hormones, neurotransmitter molecules of the nervous system, and through the immune system. The brain can affect the intestinal microbiota through the autonomic nervous system by modulating intestinal transit.
Interactions between the brain and the intestines (doi: 10.3389/fpsyt.2020.00541)
What is the link between the intestinal microbiota and depression?
Increasing evidence shows a link between the profile of the intestinal microbiota and depression through the brain-gut microbiota axis. For example, the administration of broad-spectrum antibiotics in mice leads to dysbiosis (imbalance between good and bad bacteria), depression-like behavior, and alteration of neuronal functions. This condition is reversible with probiotic treatment with Lactobacillus casei DG. Transplanting fecal matter from depressed patients into healthy mice induces depressive behavior. Antidepressant treatments would alter the intestinal microbiota. Some types of bacteria are found in smaller numbers in people with depressive disorders (Lactobacillus or Bifidobacterium). These have an anti-inflammatory effect. Other bacteria interact directly with the immune system and create inflammation. Immune system activation through this pathway could potentially lead to psychiatric symptoms. However, differences in bacterial profiles between healthy and sick individuals are still under discussion. Indeed, bacteria found in the intestines vary from one population to another, notably due to diet. However, identical or similar essential functions can be performed by a variety of different bacteria. Some researchers have therefore focused on differences in functions between healthy individuals and sick individuals. In healthy individuals, there would be more bacteria metabolizing sugars, whereas in sick patients, there would be more bacteria metabolizing proteins. In women, a link has been made between protein consumption and the severity of symptoms, but this link is limited by genetic factors. Some bacteria produce vitamins (especially vitamin B9), the low levels of which are correlated with the severity of depression symptoms. In depressive patients, these bacteria are in lower quantities. Moreover, certain disorders such as intestinal inflammation also increase this severity. Finally, intestinal bacteria such as Bifidobacterium produce molecules used for communication in the brain, including dopamine and serotonin involved in depressive disorders. Modulation of neurotransmitter production is therefore a possible means by which the intestinal microbiome can affect the brain, with a direct link to depression.
Hope for new personalized therapies
Major depressive disorders are not treated solely with medication, although they are in the frontline. Psychotherapy is complementary. Sometimes, in cases of treatment resistance, electroconvulsive therapy (a treatment in which an electric current is sent to the brain through electrodes placed on the head) is recommended. As the mechanisms underlying depression are still unknown, studying the brain-gut axis is a challenge that could lead to new therapies. For example, in mice, the administration of Bifidobacterium increases stress resistance, while the administration of betaine (a plant pigment extracted from sugar beet, which gives its red color) decreases anhedonia (inability to feel pleasure). Also in mice, injection of short-chain fatty acids alleviates depressive behaviors induced by stress. In humans, depressive symptoms improve with probiotic intake or dietary changes. Further research is needed for the development of new treatments and a more detailed understanding of the pathophysiology of depressive disorders, but the study of the brain-gut microbiota axis offers many possibilities and perspectives.
Sources :
4. INSERM. [En ligne] Paris. Dépression - Mieux la comprendre pour la guérir durablement. Publié le 14/06/2017. Modifié le 06/12/2019. Cité le 09/04/2024. https://www.inserm.fr/dossier/depression/
5. OMS. [En ligne] Genève. Trouble dépressif (dépression). Publié le 31/03/2023. Cité le 09/04/2024. https://www.who.int/fr/news-room/fact-sheets/detail/depression
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