Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice

Abstract

Gut microorganisms and the products of their metabolism thoroughly affect host brain development, function and behavior. Since alterations of brain plasticity and cognition have been demonstrated upon motor, sensorial and social enrichment of the housing conditions, we hypothesized that gut microbiota and metabolome could be altered by environmental stimuli, providing part of the missing link among environmental signals and brain effects. In this preliminary study, metagenomic and metabolomic analyses of mice housed in different environmental conditions, standard and enriched, identify environment-specific microbial communities and metabolic profiles. We show that mice housed in an enriched environment have distinctive microbiota composition with a reduction in gut bacterial richness and biodiversity and are characterized by a metabolomic fingerprint with the increase of formate and acetate and the decrease of bile salts. We demonstrate that mice treated with a mixture of formate and acetate recapitulate some of the brain plasticity effects modulated by environmental enrichment, such as hippocampal neurogenesis, neurotrophin production, short-term plasticity and cognitive behaviors, that can be further exploited to decipher the mechanisms involved in experience-dependent brain plasticity.

Dietary Fats and Cognitive Status in Italian Middle-Old Adults

“…SCSFAs activate many types of neurons in the enteric nervous system modulating neurotransmitter release such as serotonin, gamma-aminobutyric acid (GABA), and acetylcholine, which have all been implicated in the regulation of mood and behavior [ 49 ]. A recent study showed that supplementation with a mixture of SCFAs increased microbiota diversification and improved cognition and stress in healthy human participants [ 50 ]. SCFAs can also influence the production of brain-derived neurotrophic factor (BDNF), a neurotrophin that is involved in neuronal growth and plasticity [ 51 ].…”

Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice

“…Our findings extend these previously observed neurotrophic effects by identifying an increase in hippocampal BDNF in response to a HFD that is positively correlated with increasing acetic acid. Indeed, administration of acetate in mice was recently observed to promote brain plasticity and increase BDNF mRNA expression in the hippocampus ( Marrocco et al, 2022 ) underscoring the potential mechanistic role for serum acetic acid elevations to enhance brain plasticity and function.…”

Cerrado and Pantanal fruit flours affect gut microbiota composition in healthy and post‐COVID‐19 individuals: an in vitro pilot fermentation study

“…These compounds regulate numerous metabolic pathways both in the intestine and at a distant level, that is, at the level of the liver, adipose tissue, muscles, and brain. It is in fact well known that SCFAs contribute to numerous physiological effects, ranging from modulation of energy homeostasis, glucose/lipid metabolism, inflammation and even immunity and cancer (Pascale et al ., 2018; Silva et al ., 2020; Marrocco et al ., 2022).…”