Title:A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer’s-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics
Volume: 18
Issue: 7
Author(s): Miao Sun*, Wenchenyang Bao, Chengyu Huang, Ziyue Xia, Changliang Zhang, Guangxian Wang, Runxin Wang, Jiangyu Li, Shaun Roux, Qian Li, Dongmei Zou, Kai Ma*Xiaofeng Bao*
Affiliation:
- Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu,China
- Jiangsu Biodep Biotechnology, 6-C2 Dongsheng West Road, Jiangyin 214400, Jiangsu,China
- Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu,China
Keywords:
Alzheimer's Disease (AD), probiotics, in vivo imaging, dendritic spine, synaptic plasticity, inflammation.
Abstract:
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, including
depression, anxiety, and Alzheimer’s Disease (AD) and the use of probiotics as therapy for these
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 functional
outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant
to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Protein
(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 correlate
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-induced
LTPs, indicative of functional and electrophysiological effects. Moreover, we observed attenuated
AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature dendritic
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 neuroinflammation.
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.
