Serum Metabolic Profile in Schizophrenia Patients With Antipsychotic-Induced Constipation and Its relationship With Gut Microbiome

Abstract

Background and Hypothesis Antipsychotics (APs), the cornerstone of schizophrenia treatment, confer a relatively high risk of constipation. However, the mechanisms underpinning AP-induced constipation are poorly understood. Thus, we hypothesized that (1) schizophrenia patients with AP-induced constipation have distinct metabolic patterns; (2) there is more than one mechanism at play in producing this adverse drug effect; and (3) AP-associated changes in the gut microbiome are related to the altered metabolic profiles. Study Design Eighty-eight schizophrenia patients, including 44 with constipation (C) and 44 matched patients without constipation (NC), were enrolled in this study. Constipation was diagnosed by Rome IV criteria for constipation and colonic transit time using radiopaque markers (ROMs) while severity was evaluated with the Bristol Stool Form Scale (BSS) and Constipation Assessment Scale (CAS). Fasting blood samples were drawn from all participants and were subjected to non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Study Results Eleven metabolites were significantly altered in AP-induced constipation which primarily disturbed sphingolipid metabolism, choline metabolism, and sphingolipid signaling pathway (P value < .05, FDR < 0.05). In the C group, changes in the gut bacteria showed a certain degree of correlation with 2 of the significantly altered serum metabolites and were associated with alterations in choline metabolism. Conclusions Our findings indicated that there were disturbances in distinct metabolic pathways that were associated with AP-induced constipation. In addition, this study presents evidence of a link between alterations in the gut microbiome and host metabolism which provides additional mechanistic insights on AP-induced constipation.

A Decrease in the Hardness of Feces with Added Glucosylceramide Extracted from Koji In Vitro—A Working Hypothesis of Health Benefits of Dietary Glucosylceramide

“…Because a decrease in fecal hardness leads to the prevention of constipation, it is hypothesized that dietary glucosylceramide may exert its physiological effects by preventing constipation. Studies have shown that antipsychotic-induced constipation can interfere with sphingolipid metabolism, choline metabolism, and the sphingolipid signaling pathway [ 57 ]. However, these hypotheses should be verified in future studies.…”

Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia

“…The liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) is a rapidly evolving analytical technique and one of the most sensitive methods in metabolomic research, providing structural and quantitative information in the identification of peptides, lipids, carbohydrates, and other metabolites in biological samples [5]. Previous metabolomic studies of biological materials (blood, urine, saliva, hair) from patients with schizophrenia [17][18][19][20][21][22] highlight the role of metabolites as potential biomarkers for schizophrenia. Metabolomic analysis of biological samples from patients based on LC-ESI-MS/MS is providing an increasing number of new disease biomarkers [23].…”