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
Affiliations
Andrea Fontana
Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Unit of Biostatistics, 71013 San Giovanni Rotondo, Italy
Mirko Manchia
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Concetta Panebianco
Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Division of Gastroenterology, 71013 San Giovanni Rotondo, Italy
Pasquale Paribello
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Carlo Arzedi
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Eleonora Cossu
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Mario Garzilli
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Maria Antonietta Montis
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Andrea Mura
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Claudia Pisanu
Unit of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy
Donatella Congiu
Unit of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy
Massimiliano Copetti
Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Unit of Biostatistics, 71013 San Giovanni Rotondo, Italy
Federica Pinna
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Bernardo Carpiniello
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy
Alessio Squassina
Unit of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy
Valerio Pazienza
Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Division of Gastroenterology, 71013 San Giovanni Rotondo, Italy
Major depressive disorder (MDD) is a common severe psychiatric illness, exhibiting sub-optimal 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.
