Gut Microbiome and Its Immune Modulation in Locally Advanced Rectal Cancer

Inclusion Criteria:

1. Age \> 19 years
2. Locally advanced rectal cancer, histologically confirmed; clinically T3/4, clinically N+, enlarged lateral lymph nodes, extramural vascular invasion (+), or mesorectal fascia (+)
3. Patients who schedule to receive total neoadjuvant therapy, including short-course radiotherapy (25 Gy in 5 fractions), followed by FOLFOX chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin)
4. Patients with ability to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorprtion
5. Patients with ability to collect their blood and stool samples

Exclusion Criteria:

1. Rectal cancer, other histologic type than adenocarcinoma (such as squamous cell carcinoma)
2. Patients who schedule to receive concurrent chemoradiotherapy or short-course radiotherapy alone followed by surgery and adjuvant chemotherapy
3. Patients who need emergent surgery or colostomy due to obstruction or bleeding
4. Prior use of proton pump inhibitors or H2 blockers, probiotics, immunosuppressive agents, and antibiotics within 4 weeks
5. Patients have concurrent medication that may interact with fluoropyrimidine or oxaliplatin (i.e. flucytosine, phenytoin, or warfarin)
6. Known prior history of severe adverse events during fluoropyrimidine or deficiency of dihydropyrimidine dehydrogenase (DPD)
7. Known prior severe hypersensitivity to platinum
8. Patients who have an active infection requiring antibiotics, antifungal, or antiviral agents
9. Prior solid organ or allogenic stem cell transplantation

11\. Patients who have clinically significant medical disease

* Cardiovascular disease \<6 months prior to enrollment (myocardial infarction, unstable angina, coronary artery bypass surgery or percutaneous coronary intervention)
* Cerebral vascular accident/stroke (\<6 months prior to enrollment)
* Congestive heart failure (≥New York Heart Association (NYHA) Classification Class II)
* Uncontrolled hypertension by standard therapy: systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg
* Serious cardiac arrhythmia requiring medication 12. Pregnant women 13. Patients who have psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements