Non-Invasive, MultiOmic and MultiCompartmental Biomarkers of Reflux Disease: A Systematic Review

ABSTRACT Background and Aims Gastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). Our group has identified predictive biomarkers of GERD in particulate exposed 1 st responders with OAD. Additionally, GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD. Methods A systematic review of PubMed and EMBASE was performed on February 22, 2022 utilizing keywords focusing on reflux disease and biomarkers. The study was registered with PROSPERO (2022-CRD42022301543). We included: original human studies in English, published after December 31, 2009 focusing on non-invasive biomarkers of GERD. Reflux related conditions included Nonerosive Reflux Disease (NERD) Laryngopharyngeal Disease (LPR), Erosive Esophagitis (EE) and Barretts Esophagus (BE). Predictive measures were synthesized and bias assessed. Results Primary search identified 241 studies. After removing duplicates and applying inclusion/exclusion criteria n=15 articles were identified. Salivary pepsin was the most studied biomarker (n=5) with a significant sensitivity and specificity for GERD and LPR detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest area under curve the receiver operator curve(ROC AUC ) 0.94(95% CI; 0.90-0.7). An oral microbiome model including Lautropia , Streptococcus and Bacteroidetes showed the greatest discrimination between BE and controls vs Lautropia alone; sensitivity of 96.9%, specificity of 88.2% and ROC AUC of 0.94(0.81-1.00). Conclusion Prior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability and accuracy of these biomarkers more studies are warranted. WHAT YOU NEED TO KNOW BACKGROUND Gastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD. FINDINGS Salivary pepsin was the most studied biomarker with a significant sensitivity and specificity for GERD detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest ROC AUC . An oral microbiome model including Lautropia, Streptococcus and Bacteroidetes showed the greatest discrimination between Barrette’s Esophagus and controls vs Lautropia alone. IMPLICATIONS FOR PATIENT CARE Prior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability, accuracy and clinical utility of these biomarkers more studies are warranted.