Age-related changes in gut microbiota composition have been implicated in brain aging and cognitive decline, acting through the gut-brain axis on amyloid accumulation, tau pathology, synapse damage, and glial activation. Live microbial approaches such as probiotics, prebiotics, and fecal microbiota transplantation address this mechanism, but they still suffer from low efficacy and unknown safety issues. We tested whether abdominal ultrasound, an approach that does not involve microbes, can alleviate age-related neurodegeneration in the senescence-accelerated mouse strain SAMP8. We treated 6-month-old male SAMP8 mice for 1 month. We then assessed behavior, neuropathology, and synaptic proteins, and quantified four pre-specified fecal bacterial taxa. Ultrasound preserved neuronal survival in the hippocampal CA3, decreased amyloid-β load in the cortex and CA3, decreased tau hyperphosphorylation in all three regions, reduced Iba-1 and GFAP immunoreactive areas, and increased synaptophysin and cortical PSD-95. Neuronal survival in the cortex and CA1 did not differ significantly from sham-treated SAMP8 mice. In the gut microbiota, ultrasound significantly reduced the enriched taxon Tyzzerella, whereas the changes in Lactobacillus, Akkermansia and Atopobiaceae were large in magnitude but not statistically significant. In an exploratory analysis, four of 64 microbiota-neuropathology associations survived correction for multiple testing. Neither object recognition memory nor spatial memory differed significantly between treated and sham-treated SAMP8 mice. Abdominal ultrasound applied to the periphery therefore reduced age-associated neuropathology in the brain, accompanied by changes in specific gut microbial taxa whose causal contribution remains untested.
