Noninvasive, MultiOmic, and Multicompartmental Biomarkers of Reflux Disease: A Systematic Review

Muhammad S Farooqi; Sanjiti Podury; George Crowley; Urooj Javed; Yiwei Li; Mengling Liu; Sophia Kwon; Gabriele Grunig; Abraham R Khan; Fritz Francois; Anna Nolan

doi:10.1016/j.gastha.2023.01.014

Noninvasive, MultiOmic, and Multicompartmental Biomarkers of Reflux Disease: A Systematic Review

Gastro Hep Adv. 2023;2(4):608-620. doi: 10.1016/j.gastha.2023.01.014. Epub 2023 Jan 21.

Authors

Muhammad S Farooqi¹, Sanjiti Podury¹, George Crowley¹, Urooj Javed¹, Yiwei Li², Mengling Liu², Sophia Kwon¹, Gabriele Grunig³, Abraham R Khan^{4

5}, Fritz Francois⁵, Anna Nolan^{1

3}

Affiliations

¹ Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine (NYUGSoM), New York, New York.
² Department of Population Health, Division of Biostatistics, NYUGSoM, New York, New York.
³ Department of Environmental Medicine, NYUGSoM, New York, New York.
⁴ Department of Medicine, Center for Esophageal Health, NYUGSoM, New York, New York.
⁵ Department of Medicine, Division of Gastroenterology, NYUGSoM, New York, New York.

Abstract

Background and aims: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has identified predictive biomarkers of GERD in particulate exposed first responders with obstructive airway disease. In addition, GERD diagnosis and treatment is costly and invasive. In light of these clinical concerns, we aimed to systematically review studies identifying noninvasive, multiOmic, and multicompartmental biomarkers of GERD.

Methods: A systematic review of PubMed and Embase was performed using keywords focusing on reflux disease and biomarkers and registered with PROSPERO. We included original human studies in English, articles focusing on noninvasive biomarkers of GERD published after December 31, 2009. GERD subtypes (non-erosive reflux disease and erosive esophagitis) and related conditions (Barrett's Esophagus [BE] and Esophageal Adenocarcinoma). Predictive measures were synthesized and risk of bias assessed (Newcastle-Ottawa Scale).

Results: Initial search identified n = 238 studies andn 13 articles remained after applying inclusion/exclusion criteria. Salivary pepsin was the most studied biomarker with significant sensitivity and specificity for GERD. Serum assessment showed elevated levels of Tumor Necrosis Factor-alpha in both GERD and Barrett's. Exhaled breath volatile sulfur compounds and acetic acid were associated with GERD. Oral Microbiome: Models with Lautropia, Streptococcus, and Bacteroidetes showed the greatest discrimination between BE and controls vs Lautropia; ROC_AUC 0.94 (95% confidence interval; 0.85-1.00).

Conclusion: Prior studies identified significant multiOmic, multicompartmental noninvasive biomarker risks for GERD and BE. However, studies have a high risk of bias and the reliability and accuracy of the biomarkers identified are greatly limited, which further highlights the need to discover and validate clinically relevant noninvasive biomarkers of GERD.

Keywords: Barrett’s esophagus; Biomarkers; GERD; Reflux Disease; Systematic Review.

Abstract

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