Effect of Probiotic Fungi against Cognitive Impairment in Mice via Regulation of the Fungal Microbiota–Gut–Brain Axis

Abstract

The fungal microbiota may be involved in the regulation of cognition and behavior, while the role of probiotic fungi against cognitive impairment is unclear. Here, we explored the idea that probiotic Saccharomyces boulardii could participate in the regulation of microglia-induced neuroinflammation in Alzheimer's disease (AD) model mice. Cognitive deficits, deposits of amyloidβ (Aβ) and phosphorylation of tau, synaptic plasticity, microglia activation, and neuroinflammatory reactions were observed. The expression levels of Toll-like receptors (TLRs) pathway-related proteins were detected. Meanwhile, intestinal barrier integrity and fungal microbiota composition were evaluated. Our results showed fungal microbiota dysbiosis in APP/PS1 mice, which might result in the neuroinflammation of AD. The increased levels of interleukin (IL)-6, IL-1β, and cluster of differentiation 11b (CD11b) were observed in APP/PS1 mice, which were associated with activation of microglia, indicative of a broader recognition of neuroinflammation mediated by fungal microbiota compared to hitherto appreciated. Probiotic S. boulardii treatment improved dysbiosis, alleviated the neuroinflammation as well as synaptic injury, and ultimately improved cognitive impairment. Moreover, S. boulardii therapy could inhibit microglia activation and the TLRs pathway, which were reversed by antifungal treatment. These findings revealed that S. boulardii actively participated in regulating the TLRs pathway to inhibit the neuroinflammation via the gut− brain axis.

Long-term atorvastatin improves cognitive decline by regulating gut function in naturally ageing rats

“…Specific fungi in the gut may be directly associated with an increased risk of developing AD [ 53 ]. Intestinal fungal disorders are closely related to AD, but the underlying mechanisms have not been fully discovered [ 54 , 55 ]. We intend to investigate the effects of long-term atorvastatin treatment on intestinal fungi and cognitive function in the next study.…”

Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype

“…The yeast was cultured in wort which was produced through meaded malt extract. The treatment of the yeast in an electromagnetic field of super-high frequencies with electromagnetic waves in the EHF range of 30–300 GHz produced the treated yeast extract [ 19 ], after which the yeast was re-cultured at 25–28 °C for 48 h [ 28 ]. Un-treated and treated strains from Milmed AB ( , accessed on 1 November 2022) were grown under shaking overnight at 28 °C in YP (1% yeast extract, 2% bactopeptone; DIFCO), supplemented with 2% glucose or 3% glycerol, SD (yeast nitrogen base w/o amino acids 0.67%) glucose 2% or glycerol 3% media.…”

“…A strain of Saccharomyces cerevisiae isolated from “nuruk” (a traditional Korean fermentation initiator) has recently been proposed as an effective probiotic, one which is able to influence the innate and adaptive immune system, reducing in particular the levels of mRNAs for IL-1β and IFNγ [ 15 ]. Saccharomyces boulardii was supplemented to APP/PS1 mice, an AD model transgenic mice characterized by neuroinflammation dependent on microglia activation and the TLRs pathway, that after treatment recovered from dysbiosis and improved their cognitive impairment [ 19 ].…”

Regulation of microglial physiology by the microbiota

“…Fungi have already been demonstrated to promote social behavior via IL-17 signaling in neurons, 140 and to modify Alzheimer’s pathology in APP/PS1 mice via an unclarified pathway. 141 Thus, fungi may provide additional routes of microglial modulation by microbiota and are deserving of further study in both humans and mice.…”