Enhanced intestinal protein fermentation in schizophrenia

Ying Liang,Yang Shen,Zhuoran Huang,Changjun Shao,Xing Shi,Yanan Chu,Jun Yu,Jian Wang,Yu Kang,Jing Chen

doi:10.1186/s12916-022-02261-z

Abstract

BackgroundEmerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified.MethodsWe conducted a case-control study of SZ patients (case to control=100:52) by performing sequencing of the gut metagenome; measurement of fecal and plasma non-targeted metabolome; including short-, medium-, and long-chain fatty acids; and targeted metabolites, along with recorded details of daily intakes of food.ResultsThe metagenome analysis uncovered enrichment of asaccharolytic species and reduced abundance of carbohydrate catabolism pathways and enzymes in the gut of SZ patients, but increased abundance of peptidases in contrast to their significantly reduced protein intake. Fecal metabolome analysis identified increased concentrations of many protein catabolism products, including amino acids (AAs), urea, branched short-chain fatty acids, and various nitrogenous derivates of aromatic AAs in SZ patients. Protein synthesis, represented by the abundance of AA-biosynthesis pathways and aminoacyl-tRNA transferases in metagenome, was significantly decreased. The AUCs (area under the curve) of the diagnostic random forest models based on their abundance achieved 85% and 91%, respectively. The fecal levels of AA-fermentative enzymes and products uniformly showed positive correlations with the severity of psychiatric symptoms.ConclusionsOur findings revealed apparent dysbiosis in the intestinal microbiome of SZ patients, where microbial metabolism is dominated by protein fermentation and shift from carbohydrate fermentation and protein synthesis in healthy conditions. The aberrant macronutrient metabolism by gut microbes highlights the importance of nutrition care and the potential for developing microbiota-targeted therapeutics in SZ.

Highlights

Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified
Our results discovered a significantly enhanced intestinal protein fermentation in patients that shifted from carbohydrate fermentation and protein synthesis in healthy conditions
Associations between gut protein fermentation and the impairment of social behaviors we investigated whether the protein fermentation in SZ patients correlated to the severity of their psychiatric symptoms, which was reassessed by the Positive And Negative Symptom Scale (PANSS) [29] for all patients

Summary

Introduction

Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified. The etiology of SZ remains unknown and likely involves a wide range of environmental factors that affect the neurophysiological processes in genetically. Liang et al BMC Medicine (2022) 20:67 effective medications for them are scarce, leaving the huge medical need remains unmet [2, 5]. Treatment of schizophrenia relies heavily on the use of antipsychotic drugs, which regulate the neurotransmitters in the brain, and impact the metabolism of patients, often leading to weight gain, abnormal blood glucose, dyslipidemia, etc. The weight gain may be related to the activation of some neurotransmitter receptors by antipsychotic drugs, including 5-hydroxytryptamin 2A (5HT2A) and 5-HT2C receptors, and histamine H1 receptor [9]. Antipsychotic drugs can affect the expression of leptin gene, reduce leptin sensitivity, and induce weight gain

Methods

Results

Discussion

Conclusion