Liquid-State Fermented Ganoderma lucidum GANO99 Regulates Gut Microbiota and Concomitantly Modulates the Behavioral Deficits and Neurohistopathological Hallmarks of Alzheimer’s Disease in a Preclinical Transgenic Mouse Model of Alzheimer’s Disease

Amyloid beta (Aβ) is a neuropathological hallmark of Alzheimer’s disease (AD). Oxidative stress promotes intracellular accumulation of Aβ in patients with AD. The effects of liquid-state fermentation products of Ganoderma lucidum without mycelia on AD improvement or prevention have not been reported. Therefore, this study aimed to determine whether the liquid-state fermented products of G. lucidum GANO99 can alter AD pathology in the brains of APP^{NL-G-F/NL-G-F} model mice. Our results suggest that these products promote the expression of superoxide dismutase and inhibit the expression of Aβ and glial fibrillary acidic protein, thereby affecting behavioral, learning, and memory disorders in AD mice. In contrast, G. lucidum GANO99 may regulate the gut microbiota to improve AD pathology. Furthermore, these liquid-state fermented products increased the abundance of intestinal probiotics Bifidobacterium in AD mice. Clinical evidence suggests that these lactic acid bacteria can alleviate AD. Overall, the liquid-state fermented products of G. lucidum GANO99 can act as symbionts by reducing the fermentative role of intestinal microbes and chemo-heterotrophy in AD mice.