Polyphenols and Probiotics to Improve Menopausal Symptoms Via the Gut-Brain Axis

The main aim of this work is to investigate whether a combination of (poly)phenols and probiotics will improve mood, anxiety and other menopausal symptoms via a gut microbiota related mechanism. This is a double-blind randomized crossover study with a total of 16 postmenopausal women (i.e participants will be divided into two groups with 8 participants in each group) and will test the effects of 8-week daily consumption of either a combination of a (poly)phenol supplement specifically designed to target the gut microbiota and a probiotic supplement specifically designed to target the gut-brain axis or the the (poly)phenol supplement and maltodextrin (placebo).

• Mixture of (Poly)phenols and a probiotic supplement (Dietary supplement): Mixture of (Poly)phenols and a probiotic supplement
• Placebo comparator (Dietary supplement), also known as (Poly)phenols and maltodextrin: Mixture of (Poly)phenols and a placebo maltodextrin comparator

Primary outcomes

• Change in blood chemistry levels [Change from baseline to 8 and 16 weeks of the intervention]: To investigate whether a combination of (poly)phenols and probiotics intervention lowers the blood chemitry parameters compared to the baseline

Secondary outcomes

• Change in BMI (body mass index) Scores [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention affect body mass index express in kg/m\^2
• Change in the gut microbiota diversity [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention impact on the faecal microbiota composition and microbial composition express as ratio compared to the baseline levels
• Change in dietary habits [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention impact an assessment of dietary intake in the study population using a validated four-day food diary compared to the baseline levels
• Change in Quality IPAQ [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention impact an assessment of physical activity questionnaire in the study population using a validated four-day food diary compared to the baseline levels
• Change in inflammatory biomarkes [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention impact CRP, IL10,IL-6 and INFY levels in the study population using ELISA immunoassays compared to the baseline levels
• Change in SCFAs metabolites (mmol/L) [Change from baseline to 8 and 16 weeks of the intervention]: To test whether a combination of (poly)phenols and probiotics intervention impact SCFAs profile in the study population using LCMS compared to the baseline levels.

Sex: Female, ages: 48 Years to 60 Years, accepts healthy volunteers

Inclusion Criteria:

* Adults >48 years
* Post-menopausal female subjects without clinical signs or symptoms of cardiovascular disease, no menstruation cycle for more than 1 year, postmenopausal status conformed by female hormone analysis
* For intervention purposes, eligible participants are also required to have a mobile phone and be able to read and speak English.

Exclusion Criteria:

* • People with comorbid conditions that may limit participation in the study, such as a history of an acute cardiovascular event, uncontrolled hypertension, cancer or major psychiatric or cognitive problems

  * People who are already participating in a weight loss programme
  * People receiving drug treatment for lipid metabolisms (e.g., statins
  * People with a history of long-term use of medicines known to influence glucose metabolism (e.g., corticosteroids)
  * People who take antibiotics or bacterial agents (Probiotics) within 1 month
  * Pregnant women, women ready for pregnancy, and nursing mothers
  * Post-menopausal female subjects without clinical signs or symptoms of cardiovascular disease
  * acute inflammation
  * cardiac arrhythmia
  * renal failure
  * heart failure (NYHA II-IV)
  * diabetes mellitus
  * C-reactive protein > 0.5 mg/dL
  * malignant disease
  * hypotension (≤100 / 60 mm Hg)
  * Women who require hormone replacement therapy during the development of the protocol.

• ADELE COSTABILE, Study director, University of Roehampton