Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

Abstract

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia.

The Effects of the Dietary Approaches to Stop Hypertension (DASH) Diet on Metabolic Syndrome in Hospitalized Schizophrenic Patients: A Randomized Controlled Trial

“…Beneficial effects of the DASH dietary pattern on cardiometabolic parameters in people with and without diabetes mellitus were also confirmed in the recently conducted umbrella review by Chiavaroli et al [28]. However, studies on the relationship between the DASH diet and different health outcomes in people with schizophrenia are still insufficient and limited [29] and, to the best of our knowledge, there are no published RCTs evaluating the effects of the DASH diet on MetS in this specific population group.…”

The gut microbiota in neuropsychiatric disorders

“…Despite over 100-year history of research, the etiology of schizophrenia is still not fully understood, nonetheless, an interaction of environmental and genetic factors is still strongly considered (Joseph et al 2017, Nemani et al 2015. Schizophrenia typically develops at age between 15-45 years (Crow 1980) and has similar prevalence rates worldwide despite the different diagnostic criteria in various parts of the world (Arneth 2017, Sartorius et al 1986).…”

“…To make dietary interventions successful support from scientists, dieticians, family members, and neuropsychiatric clinicians is necessary (Joseph et al 2017). Further clinical trials are needed to confirm these theses.…”

Probiotics for Preventing Cognitive Impairment in Alzheimer’s Disease

“…In fact, several SCFAs produced by gut microbiota have been shown to be capable of potently inhibiting the formation of toxic soluble Aβ aggregates, in vitro [91]. A growing body of evidence has shown that circulating levels of SCFAs could affect CNS function [92,93], suggesting a functional role of SCFAs in the modulation of amyloidosis, neuroinflammation, and other AD-related conditions in the brain. Moreover, in the 3xTg-AD mice model (which rapidly develops amyloid plaques and NTFs) treated with the probiotics SLAB51, the levels of the bacterial metabolites (i.e., propionate and acetate) are elevated [55].…”