Transfer of Tumor-Bearing Mice Intestinal Flora Can Ameliorate Cognition in Alzheimer’s Disease Mice

Abstract

Background: Fecal microbiota transplant (FMT) is a potential treatment approach for many diseases. Alzheimer’s disease (AD) and cancer have been proven to have a specific antagonistic relationship to FMT. Objective: This article aims to explore whether intestinal flora transplantation from cancer individuals can ameliorate cognitive impairment. Methods: Morris water maze and object recognition tests were performed to assess cognitive function after the fecal flora from tumor-bearing and WT mice were transplanted into AD mice by gavage. The effect of flora transplantation on AD was analyzed by thioflavin T staining, western blot, and 16S RNA sequencing. Results: AD mice with FMT significantly improved short-term memory level and cognitive ability compared with Tg + NaCl group. Inflammatory factors in the plasma were regulated, and Aβ plaques burden in the hippocampus and cortex were decreased. FMT in the tumor-bearing group showed a higher significant amelioration in symptoms compared to the healthy group. 16S RNA sequencing revealed that FMT treatments could reverse the increased Firmicutes and Prevotella and the decreased Bacteroidetes, Bacteroides, and Sutterella in AD mice. AD mice transplanted with tumor-bearing mice feces additionally increased the density of Oscillospira, Odoribacter, and AF12. Furthermore, the predicted functional analyses showed that the metabolism of inorganic and organic salts in the intestinal flora of AD mice was also reversed by FMT. Conclusion: Intestinal flora transplantation from tumor-bearing mice can ameliorate the cognitive impairment of AD mice.

Impact of Donepezil Supplementation on Alzheimer’s Disease-like Pathology and Gut Microbiome in APP/PS1 Mice

“…Consistent with our findings, it has been reported that the abundance of Odoribacter , a member of SCFA-producing bacteria, was increased in the gut microbiota of AD mice with reduced Aβ deposition [ 61 ]. In addition, gut-microbiota-derived SCFAs, such as butyrate and propionic acid, can interfere with Aβ aggregation [ 62 ].…”

Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis

“…Another animal experiment has also substantiated the capacity of FMT to ameliorate cognitive decline and amyloid-like protein accumulation in AD mice ( Cheng et al, 2023 ). Hang Z et al observed that FMT treatment can reverse the GM remodeling in AD mice, also rectifying the metabolic aberrations of inorganic and organic salts in the intestinal microbiota of AD mice ( Hang et al, 2022 ). Despite predominantly being investigated in animal models, FMT holds promise as a potential avenue for treating neurodegenerative disorders, particularly AD, through mechanisms encompassing restoration of Short-Chain Fatty Acids (SCFA) and disruption of Aβ oligomers in the future.…”

“…The study discovered a possible association GM dysbiosis and AD risk, which may involve the following mechanisms: ① Gram-negative bacteria, including Bacteroidetes , in the GM produce endotoxins that activate macrophages, triggering an inflammatory response ( Stilling et al, 2016 ; Hang et al, 2022 ). ② Imbalance or dysregulation of the GM can impact the levels of short-chain fatty acids (SCFAs) and worsen cerebral Aβ burden in APP/PS1 transgenic mice ( Yadav and Lewis, 2021 ; Hang et al, 2022 ). ③ Bacterial product lipopolysaccharide (LPS) has recently been shown to be associated with the peripheral region of neuronal cell nuclei in sporadic AD, affecting the expression of amyloid precursor protein (APP) or its processing enzymes.…”

Gut microbiome-based therapies for alleviating cognitive impairment: state of the field, limitations, and future perspectives

“…A review of existing studies found that several animal experiments have demonstrated the beneficial impacts of FMT on CI. Hang et al 151 observed that in APP/PS1 mice, the transplantation of intestinal flora from tumor-bearing mice led to an improvement in plasma pro-inflammatory factors such as IL-1β and TNF-α, as well as anti-inflammatory factors like TGF-β and IL-2. This resulted in reduced neuroinflammation and protected hippocampal-related cognitive behaviors, suggesting the beneficial effects of FMT in immune regulation.…”