Altered levels of fecal short-chain fatty acids are associated with subclinical inflammation and worse cognitive performance in patients with schizophrenia

Schizophrenia is a multi-systemic disorder that is associated with lipid profile disturbances, altered glucose homeostasis and subclinical inflammation. It has been proposed that dysfunction of the gut-brain axis might underlie these alterations. Short-chain fatty acids (SCFAs) are considered to play a pivotal role in the gut-brain axis. In this study, we aimed to compare fecal levels of SCFAs in patients with schizophrenia and healthy controls (HCs), taking into consideration their relationship with common peripheral blood alterations observed in schizophrenia. The study included 100 stable outpatients with schizophrenia and 55 HCs. The levels of SCFAs (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and lactic acid) in fecal samples were measured. Also, lipid profile together with the levels of C-reactive protein, glucose and insulin were determined. The levels of isovaleric acid were significantly higher in patients with schizophrenia after co-varying for age, sex, and the adherence to the Mediterranean diet. Moreover, there were significant positive correlations of the levels of valeric acid, isovaleric acid and CRP in patients with schizophrenia. In this group of participants, higher levels of isovaleric acid were associated with significantly lower scores of delayed memory after adjustment for potential covariates and interactions with CRP levels. Our results indicate that individuals with schizophrenia show altered levels of isovaleric acid that might be associated with impairments of delayed memory. The association with cognitive impairments might be independent of interactions with immune-inflammatory processes. Longitudinal and experimental studies are needed to test causal mechanisms of observed correlations.

Automated summary

This study compared the levels of short-chain fatty acids (SCFAs) in fecal samples of patients with schizophrenia and healthy controls, and analyzed their relationship with common peripheral blood alterations observed in schizophrenia. The results showed that patients with schizophrenia had significantly higher levels of isovaleric acid compared to the healthy controls. Moreover, in patients with schizophrenia, the levels of isovaleric acid, valeric acid, and C-reactive protein were significantly positively correlated with impaired memory.