Abstract

The human gut microbiota (GM) is a complex and dynamic ecosystem that hosts trillions of commensal and potentially pathogenic microorganisms. It is crucial in protecting humans from pathogens and in maintaining immune and metabolic homeostasis. Numerous studies have demonstrated that GM has a significant impact on health and disease, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder characterized by impaired short-term memory and cognitive deficits. Patients with AD have been reported to exhibit abnormalities in GM density and species composition. Oxidative stress (OS) has been implicated in the onset and progression of AD; however, the relationship between OS and gut microbiota in AD onset and progression is not clear. Twendee X® (TwX), an oral supplement consisting of eight active ingredients, has been shown to prevent dementia in mild cognitive impairment (MCI) in humans and substantially improve cognitive impairment in mouse models of AD. This positive effect is achieved through the potency of the combined antioxidants that regulate OS; therefore, similar results cannot be achieved by a single antioxidant ingredient. To examine the impact of long-term OS elevation, as seen in AD on the body and GM, we examined GM alterations during the initial OS elevation using a two-week OS loading rat model, and examined the effects of TwX on OS and GM. Furthermore, using a questionnaire survey and fecal samples, we analyzed the impact of TwX on healthy individuals' gut bacteria and the associated effect on their quality of life (QOL). TwX was found to increase the number of bacteria species and their diversity in GM, as well as butyrate-producing bacteria, which tend to be reduced in AD patients. Additionally, TwX improved defecation condition and QOL. The gut bacteria function as part of the homeostatic function during OS elevation, and the prophylactic administration of TwX strengthened this function. The results suggest that the preventative effect of TwX on dementia may involve the GM, in addition to the other previously demonstrated effects.

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