Inclusion Criteria:  Scheduled for clinically indicated esophagogastroduodenoscopy (EGD) for diagnosis of possible non-duodenal malignancies, for surveillance of Barrett's esophagus, or for reflux, abdominal pain, or unexplained nausea/vomiting Age >= 18 years of age. Note: Because no dosing or adverse event (AE) data are currently available on the use of plecanatide or linaclotide in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable Willing to provide mandatory biospecimens as specified in the protocol Eastern Cooperative Oncology Group (ECOG) performance status =< 1 Not pregnant or breastfeeding, as determined by clinical administration of pregnancy test prior to EGD procedure. Note: The effects of plecanatide and linaclotide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 2 weeks after discontinuing study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Breastfeeding should be discontinued if the mother is treated with plecanatide or linaclotide Ability to understand and the willingness to sign a written informed consent document  Exclusion Criteria:  Prior treatment in the past week with plecanatide, linaclotide, or other agent whose primary mechanism of action is that of a GCC agonist History of allergic reactions attributed to compounds of similar chemical or biologic composition of plecanatide or linaclotide Use of any other investigational agents =< 12 weeks prior to registration Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of gastric bypass, gastric sleeve, or bariatric surgery