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. 2021 Jul 23;9(8):875.
doi: 10.3390/biomedicines9080875.

Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics

Mirko Manchia  1   2   3 , Andrea Fontana  4 , Concetta Panebianco  5 , Pasquale Paribello  1   2 , Carlo Arzedi  1   2 , Eleonora Cossu  1   2 , Mario Garzilli  1   2 , Maria Antonietta Montis  1   2 , Andrea Mura  1   2 , Claudia Pisanu  6 , Donatella Congiu  6 , Massimiliano Copetti  4 , Federica Pinna  1   2 , Valerio Pazienza  5 , Alessio Squassina  6 , Bernardo Carpiniello  1   2
Affiliations

Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics

Mirko Manchia et al. Biomedicines. .

Abstract

The gut microbiota is constituted by more than 40,000 bacterial species involved in key processes including high order brain functions. Altered composition of gut microbiota has been implicated in psychiatric disorders and in modulating the efficacy and safety of psychotropic medications. In this work we characterized the composition of the gut microbiota in 38 patients with schizophrenia (SCZ) and 20 healthy controls (HC), and tested if SCZ patients with different response to antipsychotics (18 patients with treatment resistant schizophrenia (TRS), and 20 responders (R)) had specific patterns of gut microbiota composition associated with different response to antipsychotics. Moreover, we also tested if patients treated with typical antipsychotics (n = 20) presented significant differences when compared to patients treated with atypical antipsychotics (n = 31). Our findings showed the presence of distinct composition of gut microbiota in SCZ versus HC, with several bacteria at the different taxonomic levels only present in either one group or the other. Similar findings were observed also depending on treatment response and exposure to diverse classes of antipsychotics. Our results suggest that composition of gut microbiota could constitute a biosignatures of SCZ and TRS.

Keywords: atypical antipsychotics; diet; microbiome; pharmacogenetics; pharmacogenomics; psychosis; severe mental disorders; typical antipsychotics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manu-script, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Boxplots of Chao1 index (richness) and Shannon index (alpha-diversity) calculated at the genus level in all patients affected by SCZ and HC. Yellow dot in each plot represents the median value. * p-value < 0.05.
Figure 2
Figure 2
Gut microbiota composition (i.e., mean relative abundance %) at phylum, family, genus and species levels grouped by patients affected by SCZ and HC.
Figure 3
Figure 3
Heatmaps of standardized relative abundance of bacterial populations (normalized Z-scores) identified by the penalized logistic regression analysis algorithm, at phylum (A), family (B), genus (C) and species (D) levels grouped by patients affected by SCZ and HC.
Figure 4
Figure 4
Boxplots of centroid Z-scores, computed by the penalized logistic regression analysis algorithm, which discriminated all patients affected by SCZ from HC.
See this image and copyright information in PMC

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