Adding fuel to the fire: the impact of stress on the ageing brain

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

“…Importantly, the antiinflammatory feature of butyrate also has fundamental implications for host (brain) ageing (Biagi et al, 2013(Biagi et al, , 2010Shimazu et al, 2010), especially in the light of the chronic inflammatory state known as inflamm-ageing (Franceschi et al, 2000) to which many tissues succumb, including the brain (Prenderville et al, 2015). Specifically, butyrate showed antiinflammatory effects in brain-resident macrophages (microglia), by reducing NF-κB signalling and inducing apoptosis, and thus promoting neuroprotection Huuskonen et al, 2004).…”

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Targeting the gut microbiota for pro-cognitive benefits may be particularly suited to application at the extremes of life, when brain function is more vulnerable and in a state of flux; rapid development in function characterised by increasingly complex cognitive abilities during infancy and slow decline in function accompanied by a steady reduction in specific cognitive abilities during old age (Prenderville et al, 2015). One small randomised controlled trial suggests that microbiota-targeted interventions may be beneficial in age-related cognitive decline (Chung et al, 2014).…”

“…For example, restoring intestinal permeability via the gut microbiota might be an important point of control (Kelly et al, 2015b). Similarly, promoting gut microbiota diversity during old age might improve health outcomes by mitigating the detrimental impact of aging on the CNS, which could in part be mediated via the kynurenine pathway (Claesson et al, 2012;Oxenkrug, 2007;Prenderville et al, 2015). Regulation of the stress response via the gut microbiota could also be a viable strategy where the underlying pathophysiology favours TDO activation .…”

Sex differences in the gut microbiome–brain axis across the lifespan

“…Further, the gut microbiome composition of the older subjects correlated with multiple health measures, including mood, affect, cognition and increased pro-inflammatory cytokine levels. As cytokines can both regulate mood and affect and be affected by gut microbiome function, it is possible that age-and sex-related shifts in microbial communities play a role in the senescent brain [68].…”