Clinical trial NCT06673199: The Influence of the "washoku" Diet on the Gut Microbiota in Postmenopausal Women
Official title: The Influence of the Japanese "washoku" Diet on the Composition of the Gut Microbiota and Its Metabolites in Overweight or Obese Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Menopause
Keywords: menopause
microbiota
isoflavones
Lead sponsor: Poznan University of Life Sciences
Sponsor class: OTHER
First posted: 2024-11-04
Enrollment: 40
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Postmenopausal women (n=40), aged 45-65.
Primary purpose: TREATMENT

Brief summary: Menopause is a special period in a woman's life, when a sudden drop in estrogen levels leads to the cessation of menstrual cycles. Hormonal changes and a decreasing metabolic rate contribute to weight gain and the appearance of numerous metabolic disorders, such as dyslipidemia, impaired glucose tolerance, insulin resistance, hyperinsulinemia, and type 2 diabetes. Currently, effective and inexpensive dietary therapeutic solutions are being sought to improve the health of this group of women. It is suggested that the Japanese washoku diet, which includes products rich in isoflavones, fiber (soy products) and unsaturated omega-3 fatty acids (fish, seaweed), may be a good solution, as it contributes to the regulation of hormonal balance, lowering cholesterol levels, and reducing the risk of insulin resistance. Moreover, the composition of such a diet may also affect the diversity of the intestinal microbiota and the production of its metabolites, such as short-chain fatty acids, and thus contribute to the improvement of patients' health. Taking the above into account, the aim of the study will be to assess the effect of the Japanese washoku diet on the composition of the intestinal microbiota and its metabolites in a group of overweight or obese women after natural menopause.

Specific objectives:

* Assessment of anthropometric parameters (body weight, height, waist circumference, hip circumference) and body composition and bone density.
* Assessment of parameters of carbohydrate metabolism (glucose, insulin concentration), lipid metabolism (total cholesterol (T-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and triglycerides).
* Analysis of intestinal microbiota, short-chain fatty acids in the feces of women.

Detailed description: Women who meet the criteria for inclusion in the study for a period of 4 weeks will be randomly assigned to one of two groups: 1. The intervention group will follow the principles of the healthy eating plate, which will be supplemented with elements of the washoku diet (30 g of roasted black soybeans and 5 g of wakame); 2. The control group will be covered only by the principles of the healthy eating plate.

All participants will receive a brochure with information on the recommended portion sizes of individual product groups in the daily diet, recipes for dishes based on roasted black soybeans and wakame. Before and after the study, in addition to anthropometric measurements (body weight, waist circumference, hip circumference), body composition and bone mineral density, an assessment of the diet (using a semi-quantitative questionnaire of food frequency, as well as the current recording method from the last 4 days) and the level of physical activity will be carried out. Additionally, the women will be asked to collect a daily portion of urine to assess the concentration of soy isoflavones and to determine the content of sodium, potassium and magnesium. Women will also have their blood (18 ml) collected to assess selected biochemical parameters (glucose, insulin, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and triglycerides). A stool sample will also be collected to assess the composition of the intestinal microbiota and its metabolites, i.e. short-chain fatty acids. Recruitment will take place via social networking sites, i.e. Facebook.

The following specific analyses were planned:

* Assessment of anthropometric parameters (height, body weight, hips and waist circumference)
* Analysis of body composition and bone mineral density
* Assessment of nutritional status (selected metabolic parameters such as glucose metabolism (glucose, insulin concentration), lipid metabolism (total cholesterol (T-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and triglycerides).
* Assessment of dietary habits (a semi-quantitative questionnaire on the frequency of food intake, additionally supplemented by the current recording method from the last 4 days.)
* Assessment of intestinal microbiota composition
* Assessment of fecal short-chain fatty acid concentration
* Assessment of urine soy isoflavones concentration

Normality of the obtained data distribution will be tested using the Shapiro-Wilk test. The Kruskal-Wallis test then will be used for nonnormally distributed data and the Tukey HSD test will be used for normally distributed data. A p value of less than 0.05 was considered statistically. The microbiota composition will be analyzed using RStudio (R version 4.0.3 (2020-10-10)) with packages including phyloseq, microbiome, and vegan. Taxa will be filtered by removing all those not assigned to any phylum. Only taxa with abundances over 0.25% in at least one sample will left in the dataset. All analyses of gut microbiota composition will be performed on the basis of the relative abundances (RA) of the OTUs (Operational Taxonomic Units).

The data collected in the planned studies will include the results of measurements and their statistical analyzes. All data will be collected directly by team members and coded. Detailed instructions on data collection will be prepared by the team leader and each member will need to read and receive appropriate training. All biochemical and anthropometric measurements will be performed in at least two repetitions and will be checked by another team member. All used specialized equipment will be properly calibrated before each use (scale, body composition analyzer, Nanodrop spectrophotometer).

Eligibility criteria: Inclusion Criteria:

* age 45 to 65,
* at least one year after natural menopause,
* BMI \> 25 kg/m2
* waist circumference \> 80 cm.

Exclusion Criteria:

* use of hormone replacement therapy;
* taking antibiotics or probiotics in the last 6 months from the date of commencement of the scientific experiment,
* taking medications regulating carbohydrate or lipid metabolism in the last 4 weeks from the date of commencement of the scientific experiment,
* taking medications regulating body weight in the last 3 months from the date of commencement of the scientific experiment,
* diseases of the thyroid gland, liver, heart, kidneys, digestive system, anemia, neoplastic diseases,
* smoking or alcohol consumption in amounts exceeding 100 g/week.

Primary outcomes:
measure: Change in composition of the intestinal microbiota
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in body weight
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in body composition
timeFrame: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
measure: Change in circumferences
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in lipid profile
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in glucose metabolism
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in urinary isoflavone content
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in urine pH
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in urine creatinine
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in urine sodium and magnesium
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
Secondary outcomes:
measure: Changes in results of nutrition assessment
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in bone density
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in the concentration of short-chain fatty acids in feces
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
measure: Change in intestinal barrier integrity
timeFrame: Week 0 (pre-intervention) and week 4 (post-intervention)
Other outcomes:
Locations:
city: Poznań
country: Poland
facility: Poznań University of Life Sciences
state: Wielkopolska
Study officials:
affiliation: Department of Human Nutrition and Dietetics, Poznań University of Life Sciences
name: Agata Chmurzyńska, Prof.
role: STUDY_CHAIR
References:
citation: Yang M, Wen S, Zhang J, Peng J, Shen X, Xu L. Systematic Review and Meta-analysis: Changes of Gut Microbiota before and after Menopause. Dis Markers. 2022 Jul 25;2022:3767373. doi: 10.1155/2022/3767373. eCollection 2022.
citation: Kanai T, Matsuoka K, Naganuma M, Hayashi A, Hisamatsu T. Diet, microbiota, and inflammatory bowel disease: lessons from Japanese foods. Korean J Intern Med. 2014 Jul;29(4):409-15. doi: 10.3904/kjim.2014.29.4.409. Epub 2014 Jun 27.
citation: Seura T, Fukuwatari T. Japanese Diet Score Is Associated with Gut Microbiota Composition in Young Japanese Adults. J Nutr Sci Vitaminol (Tokyo). 2019;65(5):414-420. doi: 10.3177/jnsv.65.414.
citation: Gabriel AS, Ninomiya K, Uneyama H. The Role of the Japanese Traditional Diet in Healthy and Sustainable Dietary Patterns around the World. Nutrients. 2018 Feb 3;10(2):173. doi: 10.3390/nu10020173.
citation: Takahashi TA, Johnson KM. Menopause. Med Clin North Am. 2015 May;99(3):521-34. doi: 10.1016/j.mcna.2015.01.006.