Fecal metabolite of a gnotobiotic mouse transplanted with gut microbiota from a patient with Alzheimer’s disease

Abstract

Studies of Alzheimer’s disease are based on model mice that have been altered by transgenesis and other techniques to elicit pathogenesis. However, changes in the gut microbiota were recently suggested to diminish cognitive function in patients, as well as in model mice. Accordingly, we have created model mice of the human gut microbiota by transplanting germ-free C57BL/6N mice with fecal samples from a healthy volunteer and from an affected patient. These humanized mice were stably colonized and reproduced the bacterial diversity in donors. Remarkably, performance on Object Location Test and Object Recognition Test was significantly reduced in the latter than in the former at 55 weeks of age, suggesting that gut microbiota transplanted from an affected patient affects mouse behavior. In addition, metabolites related to the nervous system, including γ-aminobutyrate, taurine, and valine, were significantly less abundant in the feces of mice transplanted with microbiota from the affected patient.

Fecal Microbiota Transplantation in Neurological Disorders

“…In a germ-free AD mouse model, FMT with conventional microbiota or conventional AD microbiota caused an increase of pathology, with the latter showing a stronger effect (Harach et al, 2017). Another study with germ-free wild-type mice found a deterioration of cognitive function with lower fecal metabolites related to the nervous system, such as GABA, in aged, and not young, mice that received AD feces compared to healthy control feces (Fujii et al, 2019). Cui et al (2018) found that the chronic noise exposureassociated increased risk for AD in mice may be mediated by the gut microbiota, and that chronic noise causes agerelated neurochemical and inflammatory dysregulation.…”

Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions

“…MS patients received FMT showed improvement in disease progression [ 212 ] and MS symptoms [ 213 ]. Fecal microbiota from AD patients to GF mice affect mouse behaviors and less production of γ-aminobutyrate, taurine, and valine in vivo [ 214 ]. The 71-year-old PD patients had FMT from healthy young donors.…”

Relationship between Alzheimer’s Disease and the Human Microbiome

“…Thus, it was revealed that the gut microbiota of the mother mouse is involved in the behavior of the offspring mouse. In addition, the authors previously reported cognitive behavior decline in germ-free mice transplanted with the microbiota of AD patients (57) (Figure 2). In this article, these data were re-analyzed by linear regression analysis (Figure 3).…”