The aim of this study is to better understand how tenapanor affects the metagenomics and metabolomics of patients with irritable bowel syndrome with constipation (IBS-C). Tenapanor is the newest FDA-approved agent for IBS-C. It is a small molecule that inhibits the NHE3 receptor, leading to impaired sodium and water absorption in the intestine. Previous clinical trials comparing tenapanor to placebo showed that a 50 mg dose of tenapanor led to increased bowel movements and decreased abdominal pain. This study consists of an 8-week treatment period in which subjects will ingest one capsule of tenapanor (50 mg per dose), twice daily, and send in stool samples following 4 weeks and 8 weeks of treatment.

Inclusion Criteria:

1. Ages 18-75 years old
2. BMI >18.5 and <35 kg/m2
3. Rome IV criteria for IBS-C for at least 6 months
4. Compliant with baseline stool submission prior to initiation of medication
5. Ability to follow verbal and written instructions
6. Ability to record daily bowel habits, including frequency, stool consistency (BSFS), and symptom severity
7. Willingness to avoid major dietary changes and use of probiotics during the study period
8. Informed consent form signed by the subjects

Exclusion Criteria:

1. History of loose stools

2. History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel syndrome (IBS-M)

3. Non-compliance with baseline stool submission

4. Previous use of tenapanor

5. GI motility obstruction or GI tract structural abnormality

6. Current use of prescribed or illicit opioids

7. History of pelvic floor dysfunction

8. Need for manual maneuvers in order to achieve a BM

9. History of GI lumen surgery at any time or other GI or abdominal operations within 60 days prior to entry into the study

10. History of high-dose stimulative or cathartic laxative abuse as judged by investigator team

11. Severe IBS-C as judged by the investigator

12. Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study

13. Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis

14. BMI of <18.5 or >35 kg/m2

15. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) or lactation

16. Absence of contraception in females of childbearing potential

17. History of allergic reaction to tenapanor

18. Administration of other FDA-approved agents for the treatment of IBS-C within 1 month prior to Screening Visit:

    • Linaclotide
    • Lubiprostone
    • Plecanatide

19. If treated with any of the following medications, dosing (or approximate frequency of 'as needed' use) must be stable for at least 30 days prior to Screening Visit and the subject must agree to maintain the same dose (or approximate frequency of 'as needed' use) or a decreased dose of medication throughout the study:

    • Probiotics
    • Bulk laxatives, fiber, and stool softeners

20. Exclusion of colonic inertia with symptoms of < 1 BM per 2 weeks

21. Subjects anticipating surgical intervention during the study

22. Known history of diabetes (type 1 or 2)

23. Subjects with recent antibiotic use (last 3 months) or anticipated antibiotic use during the study period

24. History of inflammatory bowel disease

25. Supine SBP > 160 mm Hg and/or supine DBP > 95 mm Hg (mean of two consecutive readings)

26. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit

27. History of swallowing disorders

28. History of gastric bypass or any other gastric surgery

29. History of small bowel resection (except if related to appendectomy)

30. History of gastric or duodenal ulcer

31. History of gastroparesis

32. History of abdominal radiation treatment

33. History of pancreatitis

34. History of intestinal stricture (e.g., Crohn's disease)

35. History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions

36. History of malabsorption

37. History of hepatitis B or C

38. History of human immunodeficiency virus

39. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)

40. Any other clinically significant disease interfering with the assessments of tenapanor, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)

41. HbA1c > 8.5% (> 69 mmol/mol)

43. Any relevant biochemical abnormality interfering with the assessments of tenapanor, according to the Investigator 44. Antidiabetic medications within 1 month prior to Screening Visit (except stable dose of metformin, ≤ 1500 mg/day, for at least 1 month in subjects with type 2 diabetes) 45. Medications requiring mandatory administration twice per day with meals