Medical nutritional weight loss was effective in reducing body weight and waist circumference and improving a range of cardiovascular disease risk factors in obese patients, with an average effective weight loss of 11.1 kg (about 13%) over 4 months in obese adults. However, it was found through the follow-up visit that these subjects had lost only 5.8kg from baseline and regained about half of their weight (5.1 kg, 48%) after 21 months of weight-loss intervention. In this study, intestinal flora analysis was proposed to identify the causes of individual repeated weight loss failure, structure changes of weight cycling and the advantage species of flora, and explore different intestinal microbiota（microbial genomics） in ending weight loss, obesity-related genetic characteristics (SNPs loci and RNA seq), metabolite（metabolomics）and potential interaction between appetite-related hormones and weight cycling triggers. This study aimed to provide new insights for implementing personalized weight loss programs to improve the success rate of weight loss. The obese patients who failed to lose weight repeatedly were recruited from Peking Union Medical College Hospital.

Research Contents:(1) Comparison of anthropometric, biochemical, energy consumption, and intestinal microbiota related indicators between groups; (2) Genotyping to screen out differential SNPs loci;(3) Analysis of the interaction between genes and environmental factors in different metabolic types of obesity. (4) A group of healthy volunteers with normal weight as the healthy control group.

Inclusion Criteria:

• Normal weight (18.5 ≤ BMI < 24 kg/m2) or obese (28 ≤ BMI < 35 kg/m2);
• Aged 18 to 50 years old;
• Han nationality;
• Able to follow the weight-loss prescription;
• Able to sign consent independently;
• Definition of Weight cycling: Loss weight more than once in the past 3 years, and weight regain exceeds 5% or more of the baseline weight of losing weight.

Exclusion Criteria:

• Bodyweight has changed more than ±10% in the past year;
• Taking drugs known to affect body weight (orlistat, GLP-1 receptor agonists, etc.);
• Taking drugs known to affect glucolipid metabolism (such as sulfonylureas, biguanides, acarbose, or insulin) have been taken in the past 6 months or at present; Lipid-lowering drugs such as statins, bate, niacin, and ezetimibe; Diuretics, β -blockers and other antihypertensive drugs; Glucocorticoid, thyroid hormone, etc.);
• Women who are currently pregnant or nearly 3 months breastfeeding;
• With serious eating disorders or vigorous exercise to lose weight;
• Hard physical workers;
• History of serious cardiovascular disease;
• Acute, chronic, or active gastrointestinal diseases;
• Serious systemic diseases;
• History of serious mental disorders;
• Cancer or active tumor;
• Secondary obesity or drug obesity patients: including hypothalamic obesity, pituitary obesity, hypercortisolism, and hypogonadism obesity;
• Severe liver dysfunction (ALT, AST, ALP, and TBil > the upper limit of 2.5 times reference value);
• Chronic kidney disease (eGFR < 60 mL/min/1.73 m2 or eGFR < 90 mL/min/1.73 m2 with proteinuria);
• Those who are considered by the researcher to be poor compliance or unable to complete this research well.

Exposure group: Obese individuals with a history of weight cycling and successful weight loss with the nutritional intervention program after enrollment Control group: obese people with a history of previous weight cycle and failure to lose weight with nutritional intervention programs after enrollment Healthy control group: healthy volunteers of normal weight as a control population