Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition

Abstract

Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the β-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aβ expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the β-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis.

Alleviation of Cognitive Impairment-like Behaviors, Neuroinflammation, Colitis, and Gut Dysbiosis in 5xFAD Transgenic and Aged Mice by Lactobacillus mucosae and Bifidobacterium longum

“…Lee et al reported that Proteobacteria population and LPS levels were significantly higher in aged mice than in young mice [9]. Yun et al also reported that the gut microbiota of 5xFADtransgenic mice strongly increased Proteobacteria population and LPS production [42]. However, we found that oral administration of NK41, NK46, and NKc reduced LPS levels in the blood and feces of 5xFAD-transgenic or aged mice.…”

Causal relationship between gut microflora and dementia: a Mendelian randomization study

“…Therefore, it has been used as a potential treatment to alleviate psychiatric disorders, including cognitive impairment (CI; Azad et al, 2018 ). Lactobacillales as a probiotic has been widely used in various CI-related studies, and a study was conducted to induce the expression of brain-derived neurotropic factor (BDNF), inhibit NF-κB activation, and regulate GM in mice to alleviate CI accompanied by systemic inflammation through Lactobacillus griseus ( Yun et al, 2023 ). A systematic evaluation showed increased levels of brain-derived neurotrophic factor, improved inflammatory profile, and cellular biomarker modulation in patients with dementia taking probiotic Lactobacillus ( Ruiz-Gonzalez et al, 2021 ).…”

Lactobacillus gasseri NK109 Alleviates Lipopolysaccharide-Induced Cognitive Impairment in Mice by Up-Regulating Inflammation-Mediated BDNF Expression

“…Oral administration of NK109 and heat-processed SE mix increased cognitive function in aged mice (Yun et al, 2023). Therefore, to investigate whether SE could increase the CI-ameliorating effect of NK109, we investigated the effects of N L , S E N L , and S E N H on LPS-induced CI in mice (Fig.…”