Exploring the role of gut microbiota in major depressive disorder and in treatment resistance to antidepressants

Andrea Fontana, Mirko Manchia, Concetta Panebianco, Pasquale Paribello, Carlo Arzedi, Eleonora Cossu, Mario Garzilli, Maria Antonietta Montis, Andrea Mura, Claudia Pisanu, Donatella Congiu, Massimiliano Copetti, Federica Pinna, Bernardo Carpiniello, Alessio Squassina, Valerio Pazienza

Research output: Contribution to journalArticlepeer-review


Major depressive disorder (MDD) is a common severe psychiatric illness, exhibiting suboptimal response to existing pharmacological treatments. Although its etiopathogenesis is still not completely understood, recent findings suggest that an altered composition of the gut microbiota might play a role. Here we aimed to explore potential differences in the composition of the gut microbiota between patients with MDD and healthy controls (HC) and to identify possible signatures of treatment response by analyzing two groups of MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants. Stool samples were collected from 34 MDD patients (8 TR, 19 R and 7 untreated) and 20 HC. Microbiota was characterized using the 16S metagenomic approach. A penalized logistic regression analysis algorithm was applied to identify bacterial populations that best discriminate the diagnostic groups. Statistically significant differences were identified for the families of Paenibacillaceae and Flavobacteriaceaea, for the genus Fenollaria, and the species Flintibacter butyricus, Christensenella timonensis, and Eisenbergiella massiliensis among others. The phyla Proteobacteria, Tenericutes and the family Peptostreptococcaceae were more abundant in TR, whereas the phylum Actinobacteria was enriched in R patients. Moreover, a number of bacteria only characterized the microbiota of TR patients, and many others were only detected in R. Our results confirm that dysbiosis is a hallmark of MDD and suggest that microbiota of TR patients significantly differs from responders to antidepressants. This finding further supports the relevance of an altered composition of the gut microbiota in the etiopathogenesis of MDD, suggesting a role in response to antidepressants.

Original languageEnglish
Article number311
Issue number9
Publication statusPublished - Sep 2020


  • Antidepressant resistance
  • Gut-brain axis
  • Major depressive disorder
  • Microbiota

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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