Bariatric Surgery and Gut Microbiota Changes Over Time

Official title

Longitudinal Evaluation of Gut Microbiota and Fecal Metabolome Following Roux-en-Y Gastric Bypass: Clinical Implications and Identification of Predictive Biomarkers

Overview

The goal of this observational study is to learn how bariatric surgery affects gut bacteria and gut-related metabolic products over time in adults with obesity. The study includes adults aged 18 to 65 years who are undergoing Roux-en-Y gastric bypass (RYGB) surgery, as well as adults with obesity treated with diet alone and healthy normal-weight adults. The main questions it aims to answer are: How does bariatric surgery change the composition and diversity of gut bacteria over time? How are these changes related to weight loss and improvement of obesity-related health conditions? Researchers will compare people undergoing bariatric surgery with people with obesity treated with diet alone and with healthy normal-weight individuals to see if surgery leads to specific changes in gut bacteria and stool metabolites that are linked to better clinical outcomes. Participants will: Provide stool samples at scheduled time points over 12 months Provide blood samples and undergo routine clinical assessments Take part in follow-up visits to monitor weight, metabolic health, and gastrointestinal symptoms

Detailed description

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.

Primary outcome measures

• Long-Term Changes in Gut Microbiota After Bariatric Surgery [Time frame: from enrollment up to 12 months of follow-up]

Secondary outcome measures (3)

• Comparison of Short- and Long-Read 16S Sequencing [Time frame: from enrollment up to 12 months of follow-up]
• Fecal Metabolome Changes and Predictive Microbe-Metabolite Signatures After Bariatric Surgery [Time frame: from enrollment up to 12 months of follow-up]
• Association Between Gut Microbiota and Clinical Outcomes [Time frame: from enrollment up to 12 months of follow-up]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Italy · 1 center

• Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis — Castellana Grotte

Publications

• Zhang T, Li H, Ma S, Cao J, Liao H, Huang Q, Chen W. The newest Oxford Nanopore R10.4.1 full-length 16S rRNA sequencing enables the accurate resolution of species-level microbial community profiling. Appl Environ Microbiol. 2023 Oct 31;89(10):e0060523. doi: 10.1128/aem.00605-23. Epub 2023 Oct 6. PMID 37800969
• Oehler JB, Wright H, Stark Z, Mallett AJ, Schmitz U. The application of long-read sequencing in clinical settings. Hum Genomics. 2023 Aug 8;17(1):73. doi: 10.1186/s40246-023-00522-3. PMID 37553611
• Salazar N, Ponce-Alonso M, Garriga M, Sanchez-Carrillo S, Hernandez-Barranco AM, Redruello B, Fernandez M, Botella-Carretero JI, Vega-Pinero B, Galeano J, Zamora J, Ferrer M, de Los Reyes-Gavilan CG, Del Campo R. Fecal Metabolome and Bacterial Composition in Severe Obesity: Impact of Diet and Bariatric Surgery. Gut Microbes. 2022 Jan-Dec;14(1):2106102. doi: 10.1080/19490976.2022.2106102. PMID 35903014
• Palleja A, Kashani A, Allin KH, Nielsen T, Zhang C, Li Y, Brach T, Liang S, Feng Q, Jorgensen NB, Bojsen-Moller KN, Dirksen C, Burgdorf KS, Holst JJ, Madsbad S, Wang J, Pedersen O, Hansen T, Arumugam M; New Collective Author. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Genome Med. 2016 Jun 15;8(1):67. doi: 10.11 PMID 27306058
• De Luca M, Shikora S, Eisenberg D, Angrisani L, Parmar C, Alqahtani A, Aminian A, Aarts E, Brown W, Cohen RV, Di Lorenzo N, Faria SL, Goodpaster KPS, Haddad A, Herrera M, Rosenthal R, Himpens J, Iossa A, Kermansaravi M, Kow L, Kurian M, Chiappetta S, LaMasters T, Mahawar K, Merola G, Nimeri A, O'Kane M, Papasavas P, Piatto G, Ponce J, Prager G, Pratt JSA, Rogers AM, Salminen P, Steele KE, Suter M, PMID 39320627

Identifiers

NCT: NCT07381140 · RC2026-30

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗