Abstract
Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain TNF-α, and memory improvement compared to no treatment controls. Although antibiotics treatment did not produce these multiple changes in brain cytokines, memory, or gliosis, it did decrease Aβ plaque load and colon cytokines in AppNL-G-F males. The intestinal cytokine milieu and splenocyte phenotype of female but not male AppNL-G-F mice indicated a modest proinflammatory innate response following probiotic treatment compared to controls, with an adaptive response following antibiotics treatment in male AppNL-G-F mice. Overall, these results demonstrate the beneficial effects of probiotic only in AppNL-G-F females, with minimal benefits of antibiotics or synbiotic feeding in male or female mice.
Highlights
Accumulating evidence suggests that bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS) and the gut microbiota plays a 4.0/).central role in this interaction
We provided a combination of two broad-spectrum non-absorbable antibiotics, vancomycin and neomycin, along with an anti-fungal, pimaricin, (ABX) in the drinking water for ten days to C57BL/6J and AppNL-G-F mice to deplete intestinal bacterial communities, followed by treatment with either a probiotic or a prebiotic in their diet for
Since Aβ levels were reduced following VSL#3 supplementation and antibiotics treatment in females and males, respectively, we examined whether the associated gliosis would be affected
Summary
Accumulating evidence suggests that bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS) and the gut microbiota plays a 4.0/).central role in this interaction. Recent advances in research of Alzheimer’s disease (AD) etiology points towards an altered gut microbiota leading to a peripheral/systemic inflammatory response that affects brain functions [14,15,16]. The intestinal microbiota has a profound impact on shaping the host immune system It regulates both the innate and adaptive immune systems by stimulating B cell and antibody responses and the differentiation of T helper cells [19]. The spore-forming component of indigenous intestinal microbiota belonging to the genus Clostridium promotes the accumulation of regulatory T cells (Tregs), which are anti-inflammatory and prevent gut inflammation [22]. Neuroimmune modulation by the microbiota regulates responses to neuroinflammation, brain injury, autoimmunity, and neurogenesis and, contributes to the etiopathogenesis or manifestation of neurodevelopmental, psychiatric, and neurodegenerative diseases [23]
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