Background. Epigenetic changes associated with etiology and pathogenesis are currently being researched as disease biomarkers in cancer and neurodegenerative diseases (NDs). Wastewater-based epidemiology (WBE) is an untapped resource to survey for epigenetic biomarkers associated with diseases to inform public health experts at a regional level. Urine and fecal liquid biopsy sampling is currently being used to identify and monitor epigenetic biomarkers of gastric and urinary cancers but not NDs. Methods. We conducted four PRISMA systematic literature reviews in Scopus from December 2021 to January 2022 for publications reporting disease biomarkers found in wastewater (n=313), epigenetic biomarkers shed in urine or feces (n=231), epigenetic biomarkers associated with NDs (n=420), and factors or comorbidities associated with epigenetic changes in AD, PD, or ALS (n=213). Results. Studies of wastewater biomarkers, urine and fecal liquid biopsy epigenetic factors, and factor exposure epigenetics in AD, PD and ALS are primarily confined to the U.S., Europe, and southeastern Asia. The most common bioindicator organisms of disease found in wastewater are bacteria. Individual biomarkers from liquid biopsy with the highest sensitivity and specificity within multiple panels, tested primarily for methylation, include RUNX3, SOX1, IRF8, and DAPK. Of the epigenetic biomarkers found in brain or blood specimens of ND patients, global hyper or hypomethylation was reported compared to controls. Epigenetic marks associated with factors driving AD, PD, or ALS are primarily DNA methylation and histone modification. While heavy metals are quantified in wastewater to inform human risk of disease, AD is associated with air pollution (increased active marks) and lead (hypoacetylation) in H3K9me3 and H3K9me2 and PD is associated with paraquat (differential acetylation), manganese (hypoacetylation), and dieldrin (hyperacetylation). Discussion. Known epigenetic biomarkers associated with NDs may be identifiable in cells or cell-free DNA shed into liquid biopsy and wastewater. Improved geospatial tagging of epigenetic biomarkers and factor exposure studies will lead to earlier interventions through epigenetic biomarker detection using WBE methodology.

Epigenetic biomarkers of neurodegenerative disease in wastewater: Lessons from liquid biopsy of cancer

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ACS Fall 2022

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