Conference Coverage

The gut a new therapeutic target for major depression?


The gut microbiota differs significantly between patients with major depressive disorder (MDD) and healthy individuals and may be modifiable with a probiotic diet to improve stress and depression scores, two new studies suggest.

Illustration of gut-brain connection ChrisChrisW/iStock/Getty Images

In one study, investigators compared stool samples between patients with MDD and healthy controls. They found significant differences in bacterial profiles between the two groups, as well as between patients who responded vs those who were resistant to treatment.

“This finding further supports the relevance of an altered composition of the gut microbiota in the etiopathogenesis of MDD and suggests a role in response to antidepressants,” coinvestigator Andrea Fontana, MSc, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, said in an interview.

Results from the second study showed significant improvements in self-reported stress, anxiety, and depression scores in healthy individuals following a “psychobiotic” diet (using probiotics or prebiotics to manipulate the microbiota to improve mental health) that was rich in fruit, vegetables, and fermented foods vs. those who received dietary advice alone.

The investigators, led by Kirsten Berding, PhD, APC Microbiome Ireland, University College Cork, Ireland, now plan on testing their psychobiotic diet in patients with MDD and hope the findings could be helpful in “the development of adjuvant therapeutic opportunities” where pharmacologic treatment is not effective.

Both studies were presented at the virtual congress of the European College of Neuropsychopharmacology, held online this year because of the COVID-19 pandemic.

A “hallmark” of major depression

Mr. Fontana and colleagues note that the mostly suboptimal response to pharmacologic treatments among patients with MDD is one of the factors that “contributes to the large socioeconomic burden” of the disease.

Previous research shows patients with MDD have gut dysbiosis, or an imbalance in the natural flora; that antidepressants have antimicrobial properties; and that probiotics have an antibiotic effect. However, the correlation between the composition of the gut microbiota and antidepressant response is poorly understood.

The investigators recruited 34 patients with MDD (aged 18-70 years) who were in a euthymic phase and who did not have comorbid conditions that could affect the gut microbiota.

Eight patients were treatment resistant, defined as a poor response to at least two adequate trials of different antidepressant classes, while 19 were treatment responsive and seven were treatment naive.

The researchers also recruited 20 healthy individuals via word of mouth to act as the control group. There were no significant differences between patients and the control group in terms of baseline characteristics.

Genomic sequencing of bacteria obtained from stool samples showed that it was possible to distinguish between patients with MDD and the healthy individuals, especially at the family, genus, and species levels.

In particular, there were significant differences in the Paenibacillaceae and Flavobacteriaceaea families, for the genus Fenollaria, and the species Flintibacter butyricus, Christensenella timonensis, and Eisenbergiella massiliensis, among others.

Results also showed that the phyla Proteobacteria, Tenericutes, and the family Peptostreptococcaceae were more common in patients with treatment-resistant MDD, whereas the phylum Actinobacteria was more abundant in treatment responders.

Moreover, several bacteria were found only in the microbiota of patients with treatment-resistant MDD, while others were seen only in treatment-responsive patients. This made it possible to discriminate not only between treatment-resistant and -responsive patients but also between those two patient groups and healthy controls.

“The results of our study confirm that gut dysbiosis is a hallmark of MDD, and suggests that the gut microbiota of patients with treatment-resistant MDD significantly differs from responders to antidepressants,” Mr. Fontana said.


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