Calorie Restriction Intervention Induces Enterotype-associated BMI Loss in Nonobese Individuals
Condition: Healthy Volunteer
Study type: Interventional

Summary: 
      Calorie restriction (CR), which has the potential effect on weight loss and blood amino
      acids, has been demonstrated to associate with gut microbiota in humans, especially in obese
      individuals. However, studies for simultaneously evaluating enterotype-dependent impacts of
      CR on the gut microbiota and blood amino acids in nonobese individuals are still limited.

      Here, 41 nonobese individuals received a 3-week CR diet with approximately 50% fewer calories
      than a normal diet. The investigators measured individuals' BMI and blood amino acid
      concentration, along with the gut microbiota before and after the intervention. In this
      trial, 28 Enterotype Bacteroides (ETB) subjects and 13 Enterotype Prevotella (ETP) subjects
      were identified before the intervention.

      The purpose of this intervention study is to evaluate the effect of calorie restriction on
      BMI loss, amino acid, and gut microbiota in healthy volunteers of two different enterotypes
      and provide useful insights for potential application of gut microbiome stratification in
      personalized nutrition intervention.
    

Detailed description: 
      1. Volunteer Recruitment

           Volunteer-wanted posters were propagated at the China National Gene Bank in Shenzhen
           from March to April 2017. A non-obese healthy volunteer was considered if his/her BMI
           less than 28 kg/m2. 50 individuals met all the criteria and were recruited in this
           study, and 41 individuals (24 females and 17 males aged 30 ± 6 years old) completed the
           whole intervention. The study was approved by the institutional review board on
           bioethics and biosafety of BGI-Shenzhen, Shenzhen (NO. BGI-IRB 17020). All participates
           were fully informed of the design and purpose of this intervention study and signed a
           written informed consent letter.

        2. Experiment Process

           The study included a one-week run-in period (baseline) and a three-week CR dietary
           intervention period. During the first week (run-in period), all healthy volunteers
           consumed their usual diet and were encouraged to avoid yogurt, high-fat foods, and
           alcohol. The CR diet was comprised of ~50% calories of a normal-calorie diet (female,
           1000kcal/day; male, 1200kcal/day). It was designed with carbohydrate, fat, and protein
           as approximately 55%, 30% and 15% of the total energy intake respectively, according to
           the Dietary Guidelines for Chinese Residents (2016) and nutritionally balanced and a
           recent large nutritional study in China. Common foods in low-calorie diets such as rice,
           vegetables, eggs, pork, and beef were prepared in the investigators' study center to
           control experimental variables introduced by different foods and calorie estimation
           errors.

           Traditional Chinese cooking style - boiled, stir-fried and stewed, were applied for the
           foods. For each meal, digital scales were used to measure the nutritional and caloric
           values of different foods and total meal for males and females respectively.

        3. Sample and Data Collection

      BMI, blood and fecal samples of each volunteer were collected at the investigators' study
      center at baseline and after the 3-week CR intervention. BMI was measured via the clinic
      scale. The concentrations of 31 amino acids and derivatives in the fasting serum samples were
      measured by LC-MS/MS. The gut microbial composition was determined using shotgun metagenomics
      sequencing of fecal DNA.
    

Intervention name(s): Low Calorie Diet
Intervention type(s): Behavioral
Intervention description(s): Low Calorie Diet consisted of ~50% calories of a normal-calorie diet (female, 1000kcal/day; male, 1200kcal/day)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: gut microbiota; calorie restrition dietary intervention