Leaky gut is associated with depressive disorders: new insights into microbiota-mediated epigenetic changes

Major depressive disorder (MDD) is a leading cause of disability in millions of people worldwide. Importantly, the gut microbiome may contribute to stress-related responses in patients with depression.

Recent research in the journal Genes evaluates how leaky gut may lead to depressive disorders through changes in metabolites derived from the gut microbiota.

Research: Microbiota-induced epigenetic changes in depressive disorders are targets of nutritional and probiotic treatments. Image credit: RAJ CREATIONSZ / Shutterstock.com

Leaky gut, depressive disorders and metabolites

The intestinal epithelial barrier prevents many toxins and pathogens from entering the lumen. However, certain events, such as stress, can facilitate leaky gut, increasing the risk of gastrointestinal abnormalities and depressive disorders. Other environmental factors such as pollution and consumption of residues in food such as pesticides can also disrupt intestinal permeability and alter the gut microbiome.

Of the short-chain fatty acids (SCFA), butyrate plays a key role in maintaining the proper health of the digestive tract. Previous studies have shown that any disruption in butyrate-mediated gut-blood barrier integrity can lead to depressive disorders.

Depression, mother’s diet and environmental pollutants

Maternal diet during pregnancy is essential for the neurological development of the offspring through changes in the gut microbiome. An unhealthy modern diet can lead to maternal dysbiosis and subsequently reduce the number of butyrate-producing bacteria, such as Strengthens depth. This could reduce the concentration of neuroactive metabolites in breast milk and thus increase anxiety and depression-like behavior in the offspring.

Exposure to chemicals such as pesticides can also lead to depressive disorders because it can cause abnormalities in the gut microbiome. In addition, certain pesticides, such as glyphosate, can adversely affect nervous system development and neuroplasticity by crossing the placental barrier.

Probiotics and faecal microbiota transfer (FMT) in depressive disorders

FMT involves the transfer of feces from a healthy individual into the recipient’s gastrointestinal tract. FMT has been shown to be effective in experimentally induced models of depressive disorders. In fact, one recent human study revealed that the effectiveness of FMT in alleviating MDD may be due to the effects of SCFA-producing bacteria such as Butyrvibrio and Faecalibacterium in the digestive tract.

Probiotics use epigenetic mechanisms to modulate the host’s immune response and maintain intestinal homeostasis. In mouse models Clostridium butyricum has been used to alleviate depression-like behavior due to its ability to secrete high levels of butyrate, a potent anti-inflammatory agent and epigenetic modifier.

Polyphenols, herbal medicines, antipsychotics and antidepressants

By changing the structure and distribution of the bacterial community, herbal medicines and polyphenols serve as valid candidates for alleviating depression-like behaviors. For example, crocetin, an antidepressant compound in saffron, increases its level Turicibacterium, Alistipes, and Rombouts that can relieve depression-like behavior.

Studies have shown that antipsychotics relieve depression by increasing the levels of butyrate-producing bacteria. Similarly, psychotropic drugs can trigger antidepressant effects by modulating the composition and function of gut bacteria. Antidepressants, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, also affect gut permeability, microbiome composition, and gastrointestinal function.

The role of antibiotics and vitamins related to gut microbiota

Antibiotics have been shown to alleviate depression-like behavior by facilitating the growth of beneficial bacteria such as Lactobacilli and bifidobacteria. One study demonstrated the beneficial effects of minocycline in reducing inflammation and ameliorating depression-like phenotypes, which was attributed to Lachnospiraceae and Clostridiales Family XIII, both of which facilitate butyrate production.

A lack of vitamins produced by the gut microbiome has also been linked to several neurological diseases, such as depression. These vitamins can include thiamin (vitamin B1), niacin (vitamin B3), vitamin K, and folate.

The pathogenesis of mental disorders may be due to the inability to synthesize vitamins, which may be due to intestinal dysbiosis. Previous studies have shown that maternal vitamin B6, B9 and B12 deficiency can lead to anxiety/depressive-like behavior and developmental delay in offspring through epigenetic changes.

Challenges in translating gut microbiome research into the treatment of depressive disorders

Medicines targeting the microbiome may offer many therapeutic opportunities for improving mental health. However, further research is needed to better understand how bioactive metabolites of gut microorganisms affect human physiology during depression.

Another challenge is the heterogeneity of microbiome composition between different human populations and geographic regions around the world. In the future, studies must be done in different population groups and at different stages of development to solve this problem.

Journal reference:

  • Nohesara, S., Abdolmaleky, HM, Zhou, J., & Thiagalingam, S. (2023) Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies. Genes 14(12); 2217. doi: 10.3390/genes14122217

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