Pilot Study of Salivary Bile Acids and Pepsin as Predictive Biomarkers of Reflux Disease After Sleeve Gastrectomy (ABSORB)

May 19, 2026 updated by: Esther Mans, MD, Hospital de Mataró

Prospective Pilot Study of Salivary Bile Acids and Pepsin as Predictive Biomarkers of Reflux Disease and Esophageal Injury After Sleeve Gastrectomy

The goal of this observational study is to learn whether bile acids and pepsin in saliva can help identify adults at higher risk of developing reflux-related esophageal disease after sleeve gastrectomy, including Los Angeles grade B-D erosive esophagitis and Barrett's esophagus. The study will include adults undergoing sleeve gastrectomy as part of their regular clinical care. Participants will be evaluated before and after surgery and will serve as their own comparison group over time.

The main questions it aims to answer are:

Are saliva bile acids and pepsin linked to Los Angeles grade B-D erosive esophagitis or Barrett's esophagus after sleeve gastrectomy? How do saliva bile acids and pepsin change before and after sleeve gastrectomy? Can saliva bile acids and pepsin become useful biomarkers for detecting reflux-related esophageal disease after sleeve gastrectomy? Are saliva biomarker levels linked to reflux symptoms and endoscopy results after surgery?

Researchers will compare saliva biomarker levels before and after surgery and between participants with and without reflux-related esophageal disease.

Participants will:

Provide saliva samples before surgery and at 12 and 36 months after surgery Provide fasting and post-meal saliva samples Undergo routine postoperative clinical follow-up and upper gastrointestinal endoscopy Complete reflux symptom questionnaires during follow-up

The study will also explore whether saliva biomarkers could help select participants for follow-up endoscopy after sleeve gastrectomy.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

The ABSORB study is a multicenter, prospective, observational pilot study designed to explore whether salivary bile acids and pepsin may serve as noninvasive biomarkers of reflux-related esophageal disease after sleeve gastrectomy. The study focuses on adults undergoing sleeve gastrectomy as part of routine clinical care and without previous conclusive reflux-related esophageal disease on preoperative upper gastrointestinal endoscopy.

Sleeve gastrectomy is currently one of the most commonly performed bariatric procedures worldwide because of its effectiveness for weight loss and improvement of obesity-related diseases. However, increasing evidence suggests that sleeve gastrectomy may also increase the risk of gastroesophageal reflux disease and reflux-related esophageal injury during long-term follow-up. Recent systematic reviews and meta-analyses have reported substantial rates of postoperative reflux symptoms, erosive esophagitis, proton pump inhibitor use, and de novo Barrett's esophagus after sleeve gastrectomy. Importantly, clinically significant esophageal disease may develop also in participants with mild symptoms or in those without typical reflux complaints.

Recent international guidelines and position statements from the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) recommend upper gastrointestinal endoscopic evaluation and postoperative surveillance after sleeve gastrectomy because of the risk of reflux-related esophageal disease, including erosive esophagitis and Barrett's esophagus.

However, systematic endoscopic surveillance after sleeve gastrectomy may be difficult to implement in all participants because upper gastrointestinal endoscopy is invasive, resource-intensive, and not always well tolerated. In addition, reflux symptoms alone may not reliably identify participants with clinically significant esophageal disease. For this reason, there is increasing interest in developing noninvasive biomarkers capable of identifying participants at increased risk of reflux-related esophageal injury after sleeve gastrectomy.

The mechanisms responsible for reflux after sleeve gastrectomy are likely multifactorial. Sleeve gastrectomy produces major anatomical and physiological changes in the upper gastrointestinal tract that may favor reflux of gastric and duodenal contents into the esophagus. Proposed mechanisms include increased intragastric pressure due to reduced gastric volume and compliance, disruption of the angle of His, altered esophagogastric junction anatomy, possible impairment of lower esophageal sphincter function, delayed gastric emptying in some participants, and the development or progression of hiatal hernia. Together, these changes may promote both acid reflux and duodenogastroesophageal reflux.

In addition to gastric acid exposure, reflux after sleeve gastrectomy may contain bile acids originating from the duodenum. Several studies have shown that mixed reflux containing gastric and biliary contents may produce greater esophageal mucosal injury than acid reflux alone. Bile acids remain biologically active in weakly acidic environments and may therefore contribute to esophageal injury even when acid exposure is partially controlled.

Experimental and translational studies have demonstrated that bile acids may play an important role in the pathophysiology of reflux-related esophageal disease. Hydrophobic bile acids such as deoxycholic acid and chenodeoxycholic acid have been associated with oxidative stress, DNA damage, epithelial barrier dysfunction, inflammatory signaling activation, and cellular changes related to Barrett's metaplasia. Exposure to bile acids may impair epithelial integrity by altering intercellular junctions and increasing mucosal permeability. Chronic exposure to mixed acid and bile reflux has also been linked to molecular pathways involved in Barrett's esophagus and esophageal adenocarcinoma development.

Because reflux-related esophageal injury may be asymptomatic, saliva has emerged as a promising biological fluid for reflux biomarker research. Reflux components may reach the oral cavity and be measured using sensitive laboratory techniques. Previous studies have demonstrated that bile acids can be identified and quantified in saliva using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry methods. Salivary bile acid concentrations have been reported to be higher in participants with reflux disease and Barrett's esophagus compared with controls. Specific bile acid profiles, particularly conjugated bile acids, have also been associated with more severe reflux-related disease.

Salivary pepsin has also been investigated as a noninvasive marker of reflux disease. Several studies have shown associations between salivary pepsin concentration and erosive esophagitis, reflux symptoms, and Barrett's esophagus. A prospective studiy performed after sleeve gastrectomy suggested that pepsin levels may be higher in participants with endoscopic erosive esophagitis.

Despite these findings, the role of salivary bile acids and pepsin as biomarkers of reflux-related esophageal disease after sleeve gastrectomy remains insufficiently studied. The ABSORB study was designed as a pilot proof-of-concept study to evaluate whether salivary biomarkers may help identify participants at increased risk of clinically significant postoperative esophageal disease, particularly Los Angeles grade B-D erosive esophagitis and Barrett's esophagus. The long-term objective of this research approach is to explore whether salivary bile acids and pepsin could eventually contribute to a noninvasive risk-stratification strategy capable of reducing the need for systematic postoperative endoscopic surveillance in lower-risk participants.

Participants will be evaluated before surgery and during postoperative follow-up at 12 and 36 months. Participants will therefore serve as their own comparison group over time. At each time point, fasting and post-meal saliva samples will be collected using a standardized collection protocol.

Upper gastrointestinal endoscopy is not performed as an experimental intervention in this study. Preoperative and postoperative endoscopies are part of the usual clinical follow-up protocol for people undergoing sleeve gastrectomy at the participating centers. Histologic samples will only be obtained when clinically indicated according to endoscopic findings.

Saliva samples will be processed and stored under controlled conditions. Bile acids will be analyzed using chromatography-mass spectrometry methods, and pepsin will be analyzed using immunologic methods. The study will evaluate total bile acid concentration, selected individual bile acids, pepsin concentration, and their changes over time.

Clinical, endoscopic, symptom, treatment, and laboratory data will be recorded in a secure electronic database using coded participant identifiers. The study will use standardized procedures for participant recruitment, saliva collection, sample labeling, sample storage, transport to the reference laboratory, and data entry. Data quality procedures will include predefined validation rules, review of missing or inconsistent data, and verification of key variables against clinical source records when needed.

This pilot study is intended to generate preliminary evidence on the potential role of salivary bile acids and pepsin as biomarkers of reflux-related esophageal disease after sleeve gastrectomy. The results may help define candidate biomarker thresholds, support future multicenter validation studies, and contribute to the development of noninvasive postoperative surveillance strategies after sleeve gastrectomy.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Esther Mans Muntwyler, MD, PhD
  • Phone Number: 1772 +34 937417700
  • Email: emans@csdm.cat

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Adults with severe obesity undergoing primary sleeve gastrectomy as part of routine clinical care at participating bariatric centers, without previous conclusive reflux-related esophageal disease on preoperative upper gastrointestinal endoscopy. Participants will be prospectively evaluated before and after surgery with saliva biomarker analysis, reflux symptom assessment, and routine postoperative endoscopic follow-up.

Description

Inclusion Criteria:

  • Adults aged 18 years or older undergoing sleeve gastrectomy at a participating center.
  • Indication for obesity treatment with sleeve gastrectomy according to the 2022 ASMBS-IFSO consensus criteria, with a maximum body mass index (BMI) of 50 kg/m².
  • Approved for sleeve gastrectomy by the obesity multidisciplinary committee.
  • Ability and willingness to provide informed consent for biological sample collection and analysis.
  • Ability to understand and comply with scheduled follow-up visits.

Exclusion Criteria:

  • According to Lyon 2.0 criteria, participants with previous evidence of conclusive reflux disease, including Los Angeles grade B, C, or D esophagitis, peptic stricture, or Barrett's esophagus diagnosed before surgery.
  • Bariatric procedures other than sleeve gastrectomy, including Roux-en-Y gastric bypass or revisional bariatric surgery.
  • History of other preexisting esophageal diseases.
  • Previous esophageal surgery.
  • Active cholestatic hepatobiliary disease or treatment with bile acid sequestrants, ursodeoxycholic acid, or medications that significantly alter bile acid metabolism at the time of saliva sampling or within one month before sample collection.
  • Acute infection or systemic antibiotic treatment within four weeks before saliva sample collection.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Sleeve gastrectomy cohort
Adults undergoing sleeve gastrectomy as part of routine clinical care who are prospectively evaluated before and after surgery with salivary biomarker analysis, symptom assessment, and routine postoperative endoscopic follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between salivary bile acid and pepsin concentrations and reflux-related esophageal disease after sleeve gastrectomy
Time Frame: 12 and 36 months after sleeve gastrectomy
Association between total and specific salivary bile acid concentrations as well as pepsin and the presence of Los Angeles grade B-D erosive esophagitis and/or Barrett's esophagus detected on upper gastrointestinal endoscopy.
12 and 36 months after sleeve gastrectomy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total salivary bile acid concentration before and after sleeve gastrectomy
Time Frame: Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy
Total salivary bile acid and pepsin concentrations measured in fasting and 1-hour post-meal saliva samples, recorded as continuous quantitative variables.
Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Profile of individual salivary bile acids and pepsin before and after sleeve gastrectomy
Time Frame: Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy
Concentration of individual salivary bile acids and pepsin measured in fasting and 1-hour post-meal saliva samples.
Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy
Endoscopic reflux-related esophageal disease after sleeve gastrectomy
Time Frame: 12 and 36 months after sleeve gastrectomy
Presence of Los Angeles grade B-D erosive esophagitis and/or Barrett's esophagus on upper gastrointestinal endoscopy.
12 and 36 months after sleeve gastrectomy
Severity of gastroesophageal reflux symptoms after sleeve gastrectomy
Time Frame: 12 and 36 months after sleeve gastrectomy
Presence and severity of gastroesophageal reflux symptoms assessed using reflux questionnaires.
12 and 36 months after sleeve gastrectomy
Association between salivary bile acid and pepsin concentrations and reflux symptoms
Time Frame: 12 and 36 months after sleeve gastrectomy
Association between total and specific salivary bile acid and pepsin concentrations and gastroesophageal reflux symptom severity assessed using reflux questionnaires.
12 and 36 months after sleeve gastrectomy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Mataró

Investigators

  • Principal Investigator: Esther Mans Muntwyler, MD, PhD, Hospital Universitari de Mataró, Consorci Sanitari del Maresme

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2026

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

May 19, 2026

First Submitted That Met QC Criteria

May 19, 2026

First Posted (Actual)

May 26, 2026

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 86/25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data may contain sensitive clinical and biomarker information collected as part of a multicenter observational study. Data sharing plans are currently under evaluation and will be subject to institutional policies, participant consent, and applicable data protection regulations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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