Prolonged treatment with probiotics mitigates intestinal dysfunction and enteric Alzheimer's-related pathology in senescence-accelerated mice

The manipulation of gut microbiota represents a potential therapeutic strategy to counteract gut disturbances in patients with age-related cognitive disorders. Here, we investigated the effects of a novel probiotic mixture (PM) in counteracting intestinal symptoms and enteric AD-pathology in an accelerated-senescence mouse model. SAMP8 mice were treated orally with PM at 1 × 10 9 CFU\AFU strain/mouse/day or placebo for two months. The effects of PM on in vivo colonic transit and in vitro colonic contractile activity were evaluated. Changes in cholinergic, tachykininergic and nitrergic neuron density as well as colonic amyloid-β1–42 (Aβ), HuC/D and IL-1β levels were assessed. Plasma GABA concentrations were also investigated. SAMP8 mice displayed: 1) impairments in colonic transit and in vitro contractility; 2) decrease in myenteric cholinergic, tachykininergic and nitrergic neurons; 3) increase in colonic Aβ1–42 and IL-1β levels and 4) decrease in circulating GABA concentrations. PM restored in vivo and in vitro colonic motility by normalizing enteric cholinergic, tachykininergic and nitrergic neurotransmissions and decreased enteric AD-related protein accumulation and inflammation. Finally, PM induced a modulation of plasma GABA concentrations in SAMP8 mice. Overall, PM supplementation may represent a suitable therapeutic strategy to counteract gut disturbances related to age-related cognitive disorders. • Mice with aging-related cognitive diseases display intestinal alterations. • Such changes include gut dysmotility and enteric AD-pathology, inflammation and neuroplasticity. • Probiotic mixture (PM) mitigates enteric dysfunctions in SAMP8 mice. • PM decreases enteric inflammation and AD-proteins and re-shapes enteric plasticity. • PM may represent a therapeutic option for age-related gut disturbances.