Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review.

Relationship between drugs and microbiota is bilateral. Proper composition thus function of microbiota is a key to some medications used in modern medicine. However, there is also the other side of the coin. Pharmacotherapeutic agents can modify the microbiota significantly, which consequently affects its function. A recently published study showed that nearly 25% of drugs administered to humans have antimicrobial effects. Multiple antidepressants are antimicrobials,. and antibiotics with proven antidepressant effects do exist. On the other hand, antibiotics (e.g., isoniaside, minocycline) confer mental phenotype changes, and adverse effects caused by some antibiotics include neurological and psychological symptoms which further supports the hypothesis that intestinal microbiota may affect the function of the central nervous system. Here we gathered comprehensively data on drugs used in psychiatry regarding their antimicrobial properties. We believe our data has strong implications for the treatment of psychiatric entities. Nevertheless the study of ours highlights the need for more well-designed trials aimed at analysis of gut microbiota function.

Deficit Symptomatology of Schizophrenia Is Associated with Attenuated Taste Identification: Findings from a Cross-Sectional Study.

Schizophrenia is the subject of many studies. There have been reports of taste disturbances in mental disorders. We found a possible relationship between deficit symptoms of schizophrenia and the dysgeusia of monosodium glutamate (MSG). Dysgeusia is a disorder that distorts the sense of taste. People describe all foods as tasting sweet, sour, bitter, or metallic. We aimed to verify whether the level of MSG taste perception may be related to the severity of deficit symptoms. MSG detection threshold was assessed via sublingual administration of three fluid samples containing MSG or water. The MSG samples had different concentrations in each sample. The task was to indicate which of the samples contained MSG, determine the intensity of the taste, and assess the taste as pleasant, unpleasant, or neutral. The study group included 200 patients diagnosed with paranoid schizophrenia according to ICD-10. We found a significant negative correlation between mean intensity of taste and the number of deficit symptoms. The symptoms of taste disturbances reported by the patient should be monitored by clinicians and differentiated between the actual deficits in the field of taste perception and the taste hallucinations as a symptom of psychosis. It is important to continue research in this area.

Effect of Psychobiotics on Psychometric Tests and Inflammatory Markers in Major Depressive Disorder: Meta-Analysis of Randomized Controlled Trials with Meta-Regression.

Probiotics were shown to act positively on gut-brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics-psychobiotics-using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from database inception until 22 April 2021 for randomized clinical trials in clinically proven Major Depressive Disorder (MDD) patients treated with either probiotics or placebo reporting any psychometric score (PROSPERO registration number: CRD42021253024). Ten studies with 705 randomized participants and 603 analyzed were included. The mean age of individuals was 38.43 ± 12.1 years, predominantly women (n = 461, 76.45). The mean study duration was 48.8 ± 12.3 (range = 28-62) days. The dosage ranged between 1 × 109 to 2 × 1010 colony forming units (CFU)/day. We found that probiotics might alleviate symptoms of MDD; endpoint data (pooled scores): SMD = -0.292, 95%CI = -0.577 to -0.007, p < 0.044; change scores (BDI): SMD = -0.482, 95%CI = -0.854 to -0.109, p < 0.011; DM = -4.848, 95%CI = -8.559 to -1.137, p < 0.01. The therapy tended to be more effective with time of psychobiotic supplementation (coefficient = -0.12, SE = 0.06, Z = -1.84, p = 0.06) and in men (% of females: coefficient = 0.1, SE = 0.06, Z = 1.78, p = 0.07). Psychobiotics have great potential in the treatment of MDD. However, no specific strain/strains, dosage or duration of treatment can currently be recommended.

Analysis of gut microbiota and intestinal integrity markers of inpatients with major depressive disorder.

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5-20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = -0.70, q = 0.016), Clostridia (r = -0.71, q = 0.026), Firmicutes (r = -0.67. q = 0.032), and the RF32 order (r = -0.70, p = 0.016) in the Alphaproteobacteria (r = -0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings.

Impaired hormonal regulation of appetite in schizophrenia: A narrative review dissecting intrinsic mechanisms and the effects of antipsychotics.

Cardiometabolic diseases are the main contributor of reduced life expectancy in patients with schizophrenia. It is now widely accepted that antipsychotic treatment plays an important role in the development of obesity and its consequences. However, some intrinsic mechanisms need to be taken into consideration. One of these mechanisms might be related to impaired hormonal regulation of appetite in this group of patients. In this narrative review, we aimed to dissect impairments of appetite-regulating hormones attributable to intrinsic mechanisms and those related to medication effects. Early hormonal alterations that might be associated with intrinsic mechanisms include low levels of leptin and glucagon-like peptide-1 (GLP-1) together with elevated insulin levels in first-episode psychosis (FEP) patients. However, evidence regarding low GLP-1 levels in FEP patients is based on one large study. In turn, multiple-episode schizophrenia patients show elevated levels of insulin, leptin and orexin A together with decreased levels of adiponectin. In addition, patients receiving olanzapine may present with low ghrelin levels. Post mortem studies have also demonstrated reduced number of neuropeptide Y neurons in the prefrontal cortex of patients with schizophrenia. Treatment with certain second-generation antipsychotics may also point to these alterations. Although our understanding of hormonal regulation of appetite in schizophrenia has largely been improved, several limitations and directions for future studies need to be addressed. This is of particular importance since several novel pharmacological interventions for obesity and diabetes have already been developed and translation of these developments to the treatment of cardiometabolic comorbidities in schizophrenia patients is needed.

Analysis of Gut Microbiota and Their Metabolic Potential in Patients with Schizophrenia Treated with Olanzapine: Results from a Six-Week Observational Prospective Cohort Study.

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5-20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy; in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy.

Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting.

RATIONALE: There is a worldwide prevalence of generalized anxiety and major depressive disorders (MDD). Gut⁻brain axis dysfunction, antibacterial activity, and modulatory effects of antidepressants toward intestinal bacteria have been shown both in vitro and in vivo. OBJECTIVES: In this study, we aimed to investigate the effects of hospital stay, including escitalopram administration, on gut microbiota in patients with depressive episodes. METHODS: After admission to the hospital and 7-days washout from all medications the composition of fecal microbiota samples was evaluated at baseline (W0) and after 6 weeks (W6), using 16S rRNA sequencing. The study was conducted on 17 inpatients (52.9% females), who followed the same daily hospital routine, including a standard diet and received 5⁻20 mg daily doses of escitalopram. RESULTS: At the end of treatment (W6), no change was observed in the Chao1 index. However, Shannon (median (Q1⁻Q3): W0 2.78 (2.67⁻3.02) vs. W6 3.11 (2.80⁻3.30)), and inverse Simpson (median (Q1⁻Q3): W0 9.26 (7.26⁻13.76) vs. W6 12.13 (9.17⁻15.73)) indices increased significantly compared to baseline values (False Discovery Rate p (q) = 0.031 and q = 0.011, respectively). We also found that between-subject W0 Bray⁻Curtis dissimilarities were significantly higher than W0⁻W6 within-subject dissimilarities (median (Q1⁻Q3): 0.68 (0.56⁻0.77) vs. 0.38 (0.35⁻0.52), two sided Mann⁻Whitney test p < 0.00001. The within-subject dissimilarities did not depend on sex, age, BMI, illness duration and a daily dose of escitalopram. No significant differences between taxa levels, at the studied time points, were observed when adjusted for multiple hypotheses testing procedures. CONCLUSIONS: We conclude that a six-week treatment in a psychiatric hospital setting resulted in increased alpha biodiversity in fecal microbiota, however its causal relationship with patients' mental health was not proved. We have also found that individual microbiome stability was not affected by hospitalization.