Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents metabolic dysfunction and Alzheimer’s disease-related memory loss in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet

Abstract

The pathogenesis of Alzheimer’s disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-β (Aβ) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aβ clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aβ clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aβ phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aβ burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aβ phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.

Lactobacillus paracasei KW3110 Prevents Blue Light-Induced Inflammation and Degeneration in the Retina

“…These results suggested that L. paracasei KW3110 could activate the gut immune cells inducing IL-10 production. In a previous report, oral administration of Pantoea agglomerans -derived lipopolysaccharide reduced proinflammatory cytokine expression in the blood and reduced the brain Aβ burden and memory impairment [30]. These results suggested that the regulation of cytokine levels, induced by oral administration of food constituents, might have the potential to affect the inflammatory state of the peripheral tissues through systemic blood flow.…”

Efficacy of continuous ingestion of dewaxed brown rice on the cognitive functions of the residents of elderly welfare facilities: A pilot test using crossover trial

“…Recently, in vitro studies have reported that Pantoea agglomerans LPS (LPSp) markedly increases the phagocytic activity directed at Aβ1-42 peptides in a mouse microglial cell line as well as in primary microglia isolated from the mouse brain (Kobayashi et al, 2016(Kobayashi et al, , 2017. In addition, the oral administration of LPSp markedly prevented a memory deficit in high-fat diet-fed SAMP8 mice (Kobayashi et al, 2018) Also, rice bran is a rich natural source of antioxidant polyphenols, flavonoids, phytic acid, vitamin E, and γ-oryzanol (Moure et al, 2001); these useful ingredients are lost in the rice milling process used to produce WR (Tuncel & Yılmaz, 2011 TA B L E 8 Difference of the score of each item of HDS-R in the low cognitive function group in a high concentration in rice bran. Rice bran extract as a rich source of γ-oryzanol improved impaired mitochondrial function in a cell culture AD model (Hagl et al, 2015) and affected the activation of microglia in vitro (Bhatia, Baron, Hagl, Eckert, & Fiebich, 2016).…”

Useful Cases of Patients With Developmental Disorders Improved by Oral Administration of LPS Derived fromPantoea agglomerans

“…Physiological effects of LPS are expressed via toll-like receptor 4 present on the cell surface of the host cell (11). The plant symbiotic Gram-negative bacteria Pantoea agglomerans has been shown to be a useful microorganism that coexists with plants supplying them with nitrogen and phosphorus (12,13). To date, various treatments have been tested in the clinical setting using LPS derived from P. agglomerans (LPSp) (14, 15).…”

“…Inagawa et al reported that they isolated LPSp from bacteria coexisting with wheat and that oral administration of LPSp increased the ability of macrophages to eliminate foreign substances in vivo (16). The group have also reported that the transdermal/oral administration of LPSp can improve the pathology of various chronic diseases (14,15,(17)(18)(19)(20)(21). Among them, administration of LPSp to mice as a model of Alzheimer's disease (caused by amyloid β accumulated in the brain) led to suppression of amyloid β accumulation and reduction in cognitive decline compared to control mice (17).…”

“…The group have also reported that the transdermal/oral administration of LPSp can improve the pathology of various chronic diseases (14,15,(17)(18)(19)(20)(21). Among them, administration of LPSp to mice as a model of Alzheimer's disease (caused by amyloid β accumulated in the brain) led to suppression of amyloid β accumulation and reduction in cognitive decline compared to control mice (17). Our clinic reported that treatment of 16 patients with malignant tumors using LPSp improved the symptoms of 10 patients, and three of them were completely cured (11).…”