Fecal microbiota transplantation derived from Alzheimer’s disease mice worsens brain trauma outcomes in wild-type controls

Abstract

Traumatic brain injury (TBI) cause neuroinflammation, exaggerated immune response, and, consequently, neurodegeneration. The gut microbiome is an essential modulator of the immune system, impacting in the brain. There are not effective treatments for TBI, therefore, modulating the gut microbiome may shed novel therapeutics for the damaged brain. Also, in patients with Alzheimer’s disease (AD), the microbiota has been associated with a lack of diversity, which negatively modulates the immune system. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in young mice. For this purpose, we performed fecal microbiota transplants from AD (FMT-AD) mice into young C57BL/6 (wild-type, WT) mice following TBI. Thus, FMT-AD and fecal microbiota transplants from healthy controls (FMT-young) were administered orally to young WT mice after the TBI occurred. We first determined the gut microbiota diversity and composition by analyzing fulllength 16S rRNA sequences from mouse fecal samples using the Oxford Nanopore MinION technology. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD treatment stimulates a higher relative abundance of Muribaculum intestinal and a decrease in Lactobacillus johnsonii compared FMT-young treatment in WT mice. Furthermore, WT mice exhibited larger lesion volumes, increased the number of activated microglia/macrophages cells, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. Thus, the gut microbiota from AD mice not only aggravates the neuroinflammatory response and motor recovery, but also increases the lesion size after TBI in young WT mice.

Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked?

“…In vivo studies conducted by Soriano et al in the C57BL/6 mouse model confirmed the roles of the intestinal microbiota in the pathogenesis of AD. Healthy mice treated with fecal microflora from mice with AD revealed larger areas of brain damage, increased numbers of activated microglia cells and reduced motor regeneration (Soriano et al, 2022). These studies provide the basis for the hypothesis that it is the microbiota that can improve Alzheimer's disease (AD) development; based on (Reitz, 2015;Moir et al, 2018;Megur et al, 2020;Pluta et al, 2020;Perkovic et al, 2021).…”