Background:
The brain-gut-microbiome axis has emerged as an important pathway
through which perturbations in the gut and/or microbial microenvironment can impact neurological
function. Such alterations have been implicated in a variety of neuropsychiatric disorders, includ-
ing depression, anxiety, and Alzheimer’s Disease (AD) and the use of probiotics as therapy for th-
ese diseases remains promising. However, the mechanisms underlying the gut microenvironment’s
influence on disease pathogenesis and therapy remain unclear.
Objective:
The objective of this study is to investigate the effect of a novel probiotic formula,
BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and
dendritic spine dynamics, in a mouse model of AD.
Methods:
BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and func-
tional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant
to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Pro-
tein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal
samples following probiotic treatment to assess the impact on gut microbial composition and corre-
late the changes with the above described measures.
Results:
Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long-
Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-in-
duced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed atten-
uated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature den-
dritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in
the treatment group suggests that this formulation may mediate its effects via attenuation of neu-
roinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more
varied and harbored a greater proportion of “beneficial” bacteria.
Conclusion:
Overall, our results indicate that treatment with BIOCG enhances microbial diversity
and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and
functional improvement in AD pathogenesis.