Clinical trial NCT05748080: The Apple Study: Two Apples a Day, Keep the Doctor Away?
Official title: Two Apples a Day, Keep the Doctor Away?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Microbial Colonization
Enzyme Overdose
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2023-02-28
Enrollment: 12
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to learn about the gut microbiome in healthy postmenopausal women aged 50-64. The main questions it aims to answer are:

* Investigate whether the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria could be decreased by ingestion of 2 apples a day for a period of 6 weeks
* Examine changes in gut microbiota composition, diversity, and functional capacity
* Examine feasibility of eating 2 apples a day for a period of 6 weeks

Participants will eat 2 apples a day for a period of 6 weeks.

Six weeks includes the period from the start of the study and gathering of baseline characteristics/questionnaires till the finish.

Detailed description: It is know that estrogen levels decrease after menopause. There are many different factors affecting these levels though; the gut microbiome has been identified as one of these. Not only the composition of the gut microbiota plays a role here, but also its activity is of special interest. The gut microbiota for instance produces the bacterial enzyme β-glucuronidase which has been shown to de-conjugate biliary excreted estrogens, leading to reactivation and reabsorption of estrogens into the bloodstream. It might be expected that this reabsorption results in elevated blood estrogen levels. Elevated levels of estrogen have been linked to not only development but also recurrence of breast cancer.

Apples are known for their pectin which has prebiotic properties and a potential decreasing effect on β-glucuronidase activity. In vitro studies and animal studies have already shown the β-glucuronidase decreasing impact of pectin. In humans this was never examined before.

This study aims to investigate whether it is possible to lower the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria by a simple dietary intervention. This dietary intervention consists of the ingestion of two whole apples a day, one in the morning and one in the evening, during the period of 6 weeks. Thereby this study aims to examine the feasibility of this intervention.

It is hypothesized that

1. this is a feasible intervention
2. this results in a decrease in the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria. Which would be in line with the findings of in vitro and animal studies and
3. an increase in microbial diversity

Eligibility criteria: Inclusion Criteria:

* Age 50-64
* Postmenopausal women
* Recent negative breast cancer screening (\< 6 months)

Exclusion Criteria:

* The regular consumption of one ore more apples a day
* Previous gastrointestinal surgery (excl. appendix surgery)
* Any type of cancer in history, except for basal cell carcinoma (BCC)
* Inflammatory bowel disease
* Mammography older than 6 months
* Antibiotic use within three months before fecal sampling
* Physically or mentally incapable or incompetent to sign informed consent
* Known apple allergy or complaints matching with apple allergy
* Less good dental state

Primary outcomes:
measure: The activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria
timeFrame: 6 weeks per patient
measure: Changes in gut microbiota composition, diversity, and functional capacity
timeFrame: 6 weeks per patient
measure: Feasibility of eating 2 apples a day for a period of 6 weeks
timeFrame: 6 weeks per patient
Secondary outcomes:
measure: Fecal levels of short-chain fatty acids (SCFA)
timeFrame: 6 weeks per patient
measure: Dietary intake, medication, stool classification and frequency, blood pressure, weight, length and quality of life before and after the intervention
timeFrame: 6 weeks per patient
Other outcomes:
Locations:
Study officials:
affiliation: Maastricht University Medical Center
name: Marjolein Smidt, prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: