Enhanced intestinal protein fermentation in schizophrenia

Abstract

Background 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. Methods We 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. Results The 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. Conclusions Our 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.

Implications of oral streptococcal bacteriophages in autism spectrum disorder

“…5 a, b). To solve this problem, we applied a recently developed analytical approach—a quasi-paired cohort, which is specific to identifying differential abundance from high-dimension data for a limited sample size and successfully applied it in various studies 7 , 35 – 37 . From the original samples, we reconstruct a quasi-paired cohort that includes 22 ASD vs. 22 control samples based on the pairwise distance of samples’ vial community profile, and eight high prevalent (present in >90% samples) differential phage groups are finally identified (Wilcoxon signed-rank test, FDR < 0.05, Supplementary Table 5 ).…”

The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components

“…Mounting evidence indicated that schizophrenia was associated with gut microbiota dysbiosis. For instance, a case-control study showed that gut microbiome dysbiosis was found in schizophrenia patients [ 74 ]. A cross-sectional study found that several gut bacteria could only be found in healthy participants, but were missing in patients with schizophrenia, such as Haemophilus [ 46 ].…”