<p>Alzheimer’s disease (AD) is the most common form of dementia, with a higher prevalence in women than in men. It has been suggested that the decline in estrogen production after menopause may increase the risk of developing dementia. We have previously shown that transgenic female APP/PS1 mice, overexpressing APP and PS1 proteins, develop spontaneous gut dysbiosis with a consequent dysfunctional estrobolome leading to higher estradiol excretion rate compared to age-matched wildtype (WT) females. It has been demonstrated that soluble fiber intake restores gut microbiota dysbiosis, reduces anxiety and improves cognitive function in APP/PS1 male mice. Therefore, the aim of this study was to evaluate if the intake of soluble fiber can modify the gut microbiota composition, alleviating the estrobolome dysfunction, and restoring sex-hormone alterations in female APP/PS1 mice. We confirm that six-month-old APP/PS1 female mice develop a spontaneous gut dysbiosis, an estrobolome dysfunction, and lower oestrous cycle frequencies than their WT littermates. Soluble fiber intake modulates the gut microbiota composition and increases beta-glucuronidase activity in faecal samples associated with a restoration of estradiol and DHEA plasma levels. Additionally, consuming soluble fiber affects various bacterial metabolic pathways and enhances the production of butyrate and acetate. Improved memory and cognitive performance were also observed in female APP/PS1 mice that were fed fructans. Therefore, soluble fiber intake may represent a preventive strategy to mitigate the alterations associated with the onset of reproductive senescence and dementia in females.</p>