Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics

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.

Modulation of Gut Microbial Diversity through Non-Pharmaceutical Approaches to Treat Schizophrenia

“…The significant potential of psychotic drugs to alter gut microbial composition in vitro has been observed by Macedo et al [ 54 ] and Maier et al [ 55 ]. An altered composition of gut microbiota in schizophrenia patients has also been observed very recently by Manchia et al [ 56 ]. The composition of gut microbiota in 38 schizophrenia patients, 20 health controls, 18 patients with treatment-resistant schizophrenia (TRS), and 20 responders (R) to different antipsychotics has been investigated in detail.…”

A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia

“…The 15 studies examining the gut microbiota in SZ were published between 2018 and 2021, with sample sizes ranging from 26 to 214 participants, again predominantly conducted in China (80%; N = 12/15 studies) (Table S3 ). Five studies included subgroups: first-episode or treated-SZ [ 99 ], acute-episode or in symptomatic remission [ 101 , 112 ], treatment resistant or treatment responders [ 109 ] and baseline or after treatment [ 111 ]. Overall, 15 studies in SZ including a total of 20 comparison groups were included in this systematic review.…”

“…In addition, most studies excluded controls with other physical or systemic illnesses (80%; N = 12/15 studies). However, three studies did not exclude some cardiometabolic conditions and reported their presence in the results [ 100 , 107 , 109 ].…”

“…The most common non-psychotropic medication exclusions were glucocorticoids, cytokines and biological agents (11%; N = 5/44 studies), as well as anti-diarrhoea or GI disorder medications (9%; N = 4/44 studies). Only three studies (7%) reported the use of non-psychotropic medications by participants [ 80 , 96 , 109 ] (Table S5 ).…”

“…Two studies were conducted in SZ; one study observed a reduction in the number of bacteria that discriminated cases from controls after 3 months of antipsychotic treatment [ 106 ]; and one study observed an increase in α-diversity, changes in the relative abundance of Lachnoclostridium and Romboutsia , and the potential for basal levels of these taxa to predict treatment response, after 24-weeks treatment with risperidone [ 111 ]. In addition, one study in SZ compared first-episode drug-naïve SZ patients to chronic SZ patients who had been receiving antipsychotic treatment for at least 3 months [ 99 ], and one study compared treatment participants who were treatment resistant versus treatment responders, compared with healthy controls [ 109 ].…”