Alleviation of cognitive impairment by gut microbiota lipopolysaccharide production-suppressing and in mice.

Bacterial lipopolysaccharide (LPS) is a risk factor for the outbreak of Alzheimer's disease. Therefore, we isolated NK151 and NK173 from a human fecal bacteria collection, which inhibited LPS production, and examined their effects on the K1- or LPS-induced cognitive impairment in mice. Oral gavage of NK151, NK173, or their (4 : 1) mixture (NKm) significantly alleviated K1-induced cognitive impairment-like behaviors in the Y-maze and novel object recognition tasks. Their treatments decreased IL-1β, IL-6, and TNF-α expression and NF-κB/Iba1 and LPS/Iba1 cell populations in the hippocampus, while the brain-derived neurotrophic factor (BDNF)/neuronal nuclei (NeuN) cell population and BDNF to proBNDF expression increased. They suppressed LPS-induced cognition impairment-like behaviors and neuroinflammation marker levels in the hippocampus. Treatment with them reduced K1- or LPS-induced LPS and apolipoprotein E levels in the blood and inflammatory marker levels in the colon. Furthermore, treatment with them modulated fecal Proteobacteria, Bacteroidetes, and Verrucomicrobia populations. Of these gut bacteria, Bacteroidaceae, Odoribacteraceae, Lactobacillaceae, Bifidobacteriaceae, Rikenellaceae, Helicobacteraceae, and Deferribacteraceae are correlated with cognitive function and blood and fecal LPS levels. These findings suggest that NK151 and NK173 may alleviate cognitive impairment with colitis by upregulating NF-κB-mediated BDNF expression through the suppression of fecal and blood bacterial LPS levels.