Prebiotic reduction of brain histone deacetylase (HDAC) activity and olanzapine-mediated weight gain in rats, are acetate independent

Abstract

&NA; The intestinal microbiome is emerging as a novel therapeutic target owing to the wide range of potential health benefits that could result by manipulating the microbiota composition through relatively simple interventions. Ingestion of the prebiotic Bimuno™ galacto‐oligosaccharide (B‐GOS®) is one such intervention that has been shown to attenuate olanzapine‐induced weight gain and improve cognitive flexibility in rats, potentially through mechanisms involving acetate, the major short‐chain fatty acid (SCFA) that is produced by B‐GOS® fermentation. The present study investigated the individual influences of B‐GOS® and sodium acetate intake on brain histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities, cortical and hippocampal expression of HDAC1‐4 and N‐methyl‐d‐aspartate receptor subunits in saline or olanzapine injected female rats. The effect of sodium acetate on olanzapine‐induced weight gain was also investigated. Daily ingestion of B‐GOS® for 21 days, reduced HDAC activity and hippocampal HDAC‐4, and elevated levels of cortical HDAC‐1 and HDAC‐3 mRNAs. Sodium acetate supplementation significantly decreased HAT, but not HDAC, activity and increased hippocampal HDAC‐3 and HDAC‐4 mRNAs. Olanzapine‐induced weight gain and fourteen genera of intestinal bacteria, were not influenced by sodium acetate intake. Together these data suggests the effects of B‐GOS® in rats cannot be replicated by acetate ingestion, and that mechanisms beyond the production of this SCFA are likely to underlie the psychotropic and metabolic actions of this prebiotic. HighlightsB‐GOS® inhibited brain HDAC activity, but increased cortical mRNA levels of HDAC‐1 and HDAC‐3.Sodium acetate inhibited HAT activity, and increased hippocampal mRNA levels of HDAC‐3 and HDAC‐4.Sodium acetate did not affect olanzapine‐induced weight gain.Sodium acetate intake did not alter central expression of NMDAR subunits.Fourteen genera of faecal bacteria remained unaffected by sodium acetate.