Personalized Metabolic Responses to Rapid, Slow and Resistant Starch

The study aims to investigate how individuals with varying gut microbiota composition and AMY1 gene copy number respond to three different types of starch. A 12-week trial will therefore be conducted, where all participants will go through three different 17-day interventions in a randomized order. Each intervention will contain a different type of starch:

A) Resistant starch B) Slow digestible starch C) Rapid digestible starch

Each intervention will contain a preparation day, a meal challenge test day at clinic, a 14-day dietary intervention at home followed by a follow up visit at clinic. The interventions will be separated with a 14-day wash-out period, where participants are consuming their normal food.

Blood, saliva and fecal samples will be collected during the trial, together with data from continuous glucose monitoring and body measurements. Questionnaires on dietary intake and lifestyle, food preferences, self-reported appetite, health-related quality of life, sleep quality and daytime sleepiness will also be filled out by the participants.

Up to 400 men and women with overweight or obesity will be invited for screening. Participants will provide stool-, saliva-, and fasting blood samples, alongside undergoing anthropometric measurements. Gut microbiota will be analyzed from stool samples, while saliva samples will be used to determine AMY1 copy number. This data will then be used to categorize participants into four distinct groups, based on high or low Prevotella abundance and high or low AMY1 copy number.

Participants in all four groups will undergo a three-way cross-over feeding regime containing three different types of starch: A) resistant starch (RS), B) slow digestible starch (SDS) and C) rapid digestible starch (RDS). Each treatment will start with a "meal challenge day" at the clinic, where participants will eat test foods for breakfast, containing the different types of starch, followed by a standardized lunch. During the meal challenge day, blood samples will be collected over 7 hours along with continuous glucose monitoring, saliva sampling and self-reported appetite. During the following 14 days, participants will continue to consume the test foods A, B or C for lunch and dinner at home along with continuous glucose monitoring. The at home intervention will be followed up with a clinical visit, where fasting blood samples are taken before the breakfast from the meal challenge day is repeated. After the breakfast, participants will take finger prick blood samples from home during another 4 hours. Each intervention will be followed by a 14-day wash out period before the next treatment begins.

The specific aims with the trial are:

1. To investigate differential metabolic responses (glycemia, blood lipids and inflammation biomarkers) in response to meal tolerance tests based on RS, SDS or RDS served for breakfast and dinner across individuals with high or low abundance of Prevotella and high or low AMY1 copy number.
2. To evaluate metabolic effects of chronic consumption of RS and SDS versus RDS daily for two weeks across different enterotypes and in individuals with high or low AMY1 copy number.
3. To evaluate a non-invasive method to measure redox potential in fecal samples. In exploratory analyses, the associations between fecal redox potential and responses to different starches as well as microbiota and other biomarkers will be investigated.

Eligibility Criteria:
Inclusion Criteria:

* Men and post-menopausal women
* Age 30-70 years
* BMI 27-40 kg/m2
* Waist circumference \> 102/88 cm for men/women
* Weight stable during previous 3 months (± 3 kg)
* Willingness to consume the intervention diets
* Ability to deal with the monitoring devices
* Medications stable for the previous 14 days
* Signed informed consent

Exclusion Criteria:

* Cardiovascular events (myocardial infarction or stroke) during the previous 6 months
* Diagnosis of diabetes (any type) or use of any drug who can interfere with glucose homeostasis (i.e., metformin, incretin analogues, SGLT-2 inhibitors)
* History of stomach or gastrointestinal conditions (inflammatory bowel disease, Crohn's disease, malabsorption, etc.)
* Colostomy, bowel resection, bariatric surgery or other major gastrointestinal surgery
* Renal or liver failure (creatinine \<1.7 mg/dl and alanine aminotransferase/aspartate aminotransferase \< 2 times than normal values, respectively)
* Anemia (hemoglobin below the age and sex specific normal reference ranges at screening)
* Blood donation (or participation in a clinical study with blood sampling) within 30 days prior to inclusion
* Having been treated with antibiotics within the past 3 months or planning to undergo treatment during the study period.
* Habitual use of probiotic/prebiotic supplements or foods enriched in probiotics
* Celiac disease
* Vegan/vegetarian diet (or a diet incompatible with protocol diets)
* Intense physical activity regimen (\> 7 h/week of moderate intensity or \> 3 h/week of high intensity)
* History of drug or alcohol abuse
* Not able to understand written and spoken Swedish
* Any other reason for lack of suitability for participation in the trial, as judged by the principal investor or co-principal investigator