Bariatric Surgery and Gut Microbiota Changes Over Time

Obesity is a complex and multifactorial condition associated with metabolic, inflammatory, and gastrointestinal alterations. In recent years, the gut microbiota has emerged as a key factor involved in energy balance, metabolic regulation, and systemic inflammation. Alterations in gut microbial composition and function have been consistently observed in individuals with obesity and are thought to contribute to metabolic dysfunction.

Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is one of the most effective treatments for severe obesity and its related comorbidities. Beyond weight loss, this procedure induces profound changes in gastrointestinal anatomy and nutrient flow, which may significantly influence the gut microbiota and the metabolites it produces. However, the timing, persistence, and clinical relevance of these microbial and metabolic changes over the long term are not yet fully understood.

This prospective observational study is designed to evaluate longitudinal changes in gut microbiota composition and fecal metabolome following bariatric surgery and to explore their association with clinical and metabolic outcomes. Participants undergoing bariatric surgery will be followed over a 12-month period and compared with individuals with obesity receiving dietary treatment and with healthy normal-weight individuals. This comparative approach allows the identification of changes specifically related to surgery rather than to weight loss alone or to normal temporal variability.

Gut microbiota will be analyzed using DNA-based sequencing approaches, while fecal metabolites will be assessed to capture functional changes in microbial activity. These biological data will be integrated with clinical and laboratory parameters to explore relationships between gut-related changes and outcomes such as weight loss, metabolic improvement, inflammation, and intestinal barrier function.

By providing a longitudinal and integrated view of gut microbiota and metabolome remodeling after bariatric surgery, this study aims to improve understanding of the biological mechanisms underlying surgical outcomes and to support the identification of potential biomarkers that may help predict individual responses and guide more personalized approaches to obesity management.

Inclusion criteria

(RYGB Group):

• Age between 18 and 65 years.
• Adults with a body mass index (BMI) ≥ 35 kg/m² with related comorbidities, or BMI ≥ 40 kg/m², who are candidates for Roux-en-Y gastric bypass (RYGB) surgery only.

Exclusion criteria

(RYGB Group):

• Treatment with antibiotics within the last 3 weeks, or probiotics/prebiotics within the last 4-6 weeks, or systemic corticosteroids within the 8 weeks prior to baseline (T0).
• Participation in dietary regimens or calorie restriction programs in the weeks prior to enrollment.
• Chronic inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis), ongoing enteric infections, or active neoplasms.
• Previous organ transplant or ongoing systemic immunosuppressive therapy.
• Pregnancy or breastfeeding.
• Previous major gastrointestinal surgery.
• Chronic alcohol consumption above moderate levels or substance use disorder.

Inclusion criteria

(Obese Control Group):

• Age between 18 and 65 years.
• Adults with BMI ≥ 30 kg/m² who are candidates for structured dietary treatment.

Inclusion criteria

(Healthy Control Group):

• Age between 18 and 65 years.
• Normal weight (BMI between 18.5 and 24.9 kg/m²).
• Normal metabolic function: fasting glucose below threshold, normal ALT/AST, no diagnosis of diabetes or metabolic syndrome.
• No chronic gastrointestinal diseases or conditions that could alter the gut microbiota.

Exclusion criteria

(Obese Control and Healthy Control Group):

• Use of antibiotics within the last 3 weeks or probiotics/prebiotics within the last 4-6 weeks.
• Recent gastrointestinal surgery.
• Pregnancy or breastfeeding.
• Extreme diets or recent dietary changes.
• Recent international travel that could have affected the gut microbiota.
• Medications known to influence the gut microbiota (e.g., PPIs, metformin, steroids).
• Active smoking or excessive alcohol consumption.
• Significant gastrointestinal symptoms (chronic diarrhea or constipation).