![]() Synaptic degeneration of field CA1 in the hippocampus, which receives innervation from pyramidal neurons from the entorhinal cortex, results in spatial memory decline in AD mice, which is also apparent in hippocampal atrophy and neuron loss seen in AD patients and is evaluated in mice in the form of a forced alternation Y-maze (FAY). Behavioral studies were also performed on healthy wildtype mice with no AD phenotype which served as controls for comparison of normal age-matched behavior (Old-WT and Young-WT) and provided baseline approximate values for behavioral tests. Following an incubation period of 21 days, mice were subjected to a battery of behavioral tests to investigate the effects of FMT on cognition, after which cerebral Aβ levels were evaluated. The control 5xFAD recipient mice (8–10 and 30–32 weeks old) were gavaged with normal saline (Old Tg-Control and Young Tg-Control). Young recipient mice (8–10 weeks old) received fecal slurry from healthy, younger (4–6-week) donors (Young Tg-fed young Young Tg-FY), shown using blue arrows in Figure 1. ![]() Half of the old recipient mice received oral gavage of fecal slurry obtained from healthy wild type (WT) donors of the same age (Old Tg-fed old Old Tg-FO), depicted as orange arrows in Figure 1, and the other half received oral gavage of fecal slurry from healthy, younger donors (Old Tg-fed young Old Tg-FY), depicted with green arrows in Figure 1. We show a donor age-dependent relationship between FMT and reduction of Alzheimer’s pathology as well as the efficacy of FMT in the absence of antibiotic administration. Crucially, immense potential for FMT as an AD therapeutic has been demonstrated. FMT has also been demonstrated to reduce Alzheimer pathology in a transgenic mouse model following pre-FMT antibiotic treatment to void the gut of its host microbiome. The efficacy of FMT has also been described in reducing intestinal dysbiosis in Parkinson’s mice and alleviating multiple neurological disorders. FMT has been successfully used to treat recurrent Clostridium difficile infections with expansions of its application into the treatment of other gastrointestinal disorders. Considering the changes that have been reported in the gut microbiome of AD patients, replacing or replenishing the phyla could have therapeutic implications.įMT involves the transfer of fecal material from a healthy donor to a recipient with the aim of normalizing composition and therefore function of intestinal microbial populations. Although the involvement of intestinal microbiota in the development and progression of AD has been established, its exact role has not been delineated despite early evidence of inflammatory pathway involvement. Modulating intestinal microbial composition has been shown to decrease Alzheimer’s symptoms in mice. Intestinal microbial composition of AD patients differs from healthy individuals, with AD patients observed to have increased Bacteroidetes and decreased Firmicutes and Bifidobacterium levels. Inter-individual variation as well as age-dependent changes in the human gut microbiome have been described, and gut microbial involvement has been suggested in neurodevelopmental, autoimmune diseases, movement disorders and neurodegeneration. ![]() The human microbiome has been described to have a distinct, complex role in the pathophysiology of multiple diseases. ![]()
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