Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

Abstract

Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APPSWE/PS1ΔE9 mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis.

Alzheimer’s disease and gut microbiota

“…At the same time, the onset of AD also supports the "hygiene hypothesis". Most recently, a new published study reported that antibiotic-induced perturbations in gut microbial diversity influenced neuro-inflammation and decreased A plaque deposition in a murine model of AD (Minter et al, 2016). All of these results demonstrate the pathology of AD may be associated with disturbance of gut microbiota.…”

Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease

“…The protective effects of autophagy and the proteasome are not specific to synuclienopathies, and the ability of the microbiota to modulate these critical cellular functions suggests that other amyloid disorders, such as Alzheimer's and Huntington's diseases, may be impacted by gut bacteria. In fact, recent studies have implicated the gut microbiota in promoting amyloid beta pathology in a model of Alzheimer's disease (Minter et al, 2016). Though we have explored postnatal effects of the microbiota in a model of neurodegenerative disease, our findings do not address the likely important role of microbial signals during prenatal neurodevelopment.…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…In a mouse model of AD, antibiotic treatment decreases Aβ plaque deposition (Minter et al, 2016) and germ‐free APP transgenic mice have a drastic reduction in cerebral Aβ amyloid pathology (Harach et al, 2017). Poor dental status has been linked to AD or early signs of AD (Gatz et al, 2006).…”