Leaky gut associated with depressive disorders: new insights into microbiota-induced 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 experiencing depression.

A recent study in the journal Jean It assesses how leaky gut may lead to depressive disorders through changes in metabolites derived from the gut microbiota.

Study: Microbiota-induced epigenetic changes in depressive disorders are targets for nutritional and probiotic therapies., 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 promote leaky gut, increasing the risk of gastrointestinal anomalies and depressive disorders. Other environmental factors such as pollution and consumption of residues in food products such as pesticides can also disturb gut permeability and alter the gut microbiome.

Among the short-chain fatty acids (SCFAs), butyrate is key to maintaining proper gastrointestinal health. Previous studies have shown that any disruption in butyrate-mediated gut-blood barrier integrity can lead to depressive disorders.

Depression, maternal diet, and environmental contaminants

Maternal diet during pregnancy is essential for the neurological development of the offspring through changes in the gut microbiome. Unhealthy modern diets may lead to maternal dysbiosis and subsequently reduced presence of butyrate-producing bacteria Firmicutes Phylum. This may reduce the levels of neuroactive metabolites in mother’s milk, which may increase anxiety and depression-like behaviors in the offspring.

Exposure to chemicals such as pesticides can also lead to depressive disorders, as they can cause abnormalities in the gut microbiome. Furthermore, some pesticides, such as glyphosate, can adversely affect neurodevelopment and neuroplasticity by crossing the placental barrier.

Probiotics and fecal microbiota transplantation (FMT) for depressive disorders.

FMT involves the transfer of fecal matter from a healthy individual into the gastrointestinal tract of a recipient. FMT has been shown to be effective in experimentally induced models of depressive disorders. In fact, a recent study on human subjects showed that the effectiveness of FMT in reducing MDD may be due to the abundance of SCFA-producing bacteria. butyrivibrio And faecalibacterium In the gastrointestinal tract.

Probiotics utilize epigenetic mechanisms to modulate host immune responses and maintain intestinal homeostasis. In the mouse model, clostridium butyricum It has been used to reduce depression-like behavior due to its ability to secrete high levels of butyrate, a strong anti-inflammatory agent and epigenetic modifier.

Polyphenols, herbal medicine, antipsychotics and antidepressants

By altering bacterial community composition and distribution, herbal medicine and polyphenols serve as viable candidates for reducing depression-like behavior. For example, crocetin, an antidepressant compound found in saffron, increases levels of turicibacter, alistipes, And Romboutsia, which can Reduce depression-like behavior.

Research has shown that antipsychotic drugs reduce depressive disorders by replenishing the levels of butyrate-producing bacteria. Similarly, psychotropic drugs may produce antidepressant effects by modulating the composition and function of gut bacteria. Antidepressants, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, also affect intestinal permeability, microbiome composition, and gastrointestinal function.

The role of antibiotics and gut microbiota-related vitamins

Antibiotics have been shown to be helpful in reducing depression-like behavior by facilitating the growth of helpful bacteria. lactobacilli and bifidobacteria, One study showed beneficial effects of minocycline in reducing inflammation and depression-like phenotypes, which was attributed to its abundance. Lachnospiraceae And clostridiales Family XIII, both of which facilitate butyrate production.

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

The pathogenesis of mental health disorders can be attributed to the inability to synthesize vitamins, which may be caused by gut dysbiosis. Previous studies have shown that maternal deficiency of vitamins B6, B9 and B12 can lead to anxiety/depression-like behaviors and delayed development in offspring through epigenetic changes.

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

Medicines targeted at the microbiome may offer many therapeutic opportunities to improve mental health. However, additional research is needed to better understand how bioactive metabolites of gut microorganisms affect human physiology during depression.

Another challenge is the diversity in microbiome composition between different human populations and geographic regions around the world. Future studies should be conducted in diverse populations and at different developmental periods to address this issue.

Journal Reference:

  • Nowhesra, S., Abdolmaleki, HM, Zhou, J., and Thiagalingam, S. (2023) Microbiota-induced epigenetic changes in depressive disorders are targets for nutritional and probiotic therapies. Jean 14(12); 2217. doi:10.3390/genes14122217

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