Short-chain fatty acids in patients with schizophrenia and ultra-high risk population

Abstract

BackgroundIndividuals who experience the prodromal phase of schizophrenia (SCZ), a common and complex psychiatric disorder, are referred to as ultra-high-risk (UHR) individuals. Short-chain fatty acid (SCFA) is imperative in the microbiota-gut-brain axis and brain function. Accumulating amount of evidence shows the connections between psychiatric disorders and SCFAs. This study aims to explore the underlying roles SCFAs play in SCZ by investigating the association of alterations in SCFAs concentrations with common cognitive functions in both the SCZ and UHR populations.MethodsThe study recruited 59 SCZ patients (including 15 participants converted from the UHR group), 51 UHR participants, and 40 healthy controls (HC) within a complete follow-up of 2 years. Results of cognitive functions, which were assessed by utilizing HVLT-R and TMT, and serum concentrations of SCFAs were obtained for all participants and for UHR individuals at the time of their conversion to SCZ.ResultsFifteen UHR participants converted to SCZ within a 2-year follow-up. Valeric acid concentration levels were lower in both the baseline of UHR individuals whom later converted to SCZ (p = 0.046) and SCZ patients (p = 0.036) than the HC group. Additionally, there were lower concentrations of caproic acid in the baseline of UHR individuals whom later transitioned to SCZ (p = 0.019) and the UHR group (p = 0.016) than the HC group. Furthermore, the caproic acid levels in the UHR group are significantly positively correlated with immediate memory (r = 0.355, p = 0.011) and negatively correlated with TMT-B (r = -0.366, p = 0.009). Significant differences in levels of acetic acid, butyric acid and isovaleric acid were absent among the three groups and in UHR individuals before and after transition to SCZ.ConclusionOur study suggests that alterations in concentrations of SCFAs may be associated with the pathogenesis and the cognitive impairment of schizophrenia. Further researches are warranted to explore this association. The clinical implications of our findings were discussed.

Features of gut microbiota and short-chain fatty acids in patients with first-episode depression and their relationship with the clinical symptoms

“…Butyrate affects the effect of anti-inflammatory and intestinal mucosa repair ( Liang et al, 2021 ). Acetate can serve as an energy substance for surrounding tissues, regulate fat cell differentiation, and synthesize long-chain fatty acids, cholesterol, glutamine, β-hydroxybutyric acid, and other substances ( Peng et al, 2021 ) that are important components of SCFAs.…”

Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations

“…Another recent clinical study showed that alterations in concentrations of SCFAs can be linked to the pathogenesis and the cognitive impairment of schizophrenia. Additionally, a significantly lower concentration of valeric acid was reported in schizophrenia patients compared to healthy controls [83]. According to the "membrane hypothesis of schizophrenia", the abnormal production of SCFAs occurring by the altered composition of the gut microbiome may result in the activation of microglia and then disrupt cell membrane metabolism [84].…”

The Gut–Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production

“…Especially noteworthy within the context of schizophrenia are short-chain fa y acids (SCFAs), which are metabolic byproducts produced by gut microbes during the fermentation process [23][24][25]. SCFAs have been found to cross the blood-brain barrier and can influence CNS activity, including the modulation of microglia activity and cytokine production [26] Dysregulation of neurotransmi ers like glutamate, γ-aminobutyric acid (GABA), dopamine, and serotonin, produced by gut microbes or their precursor molecules, may also contribute to CNS disorders, including schizophrenia [27][28][29][30][31][32][33][34][35].…”