Background:

Inflammatory bowel disease (IBD) is a term used to describe disorders that cause long-term inflammation in the digestive tract. Symptoms include stomach pain, diarrhea, and bleeding. Crohn's disease and ulcerative colitis are the 2 main types of IBD. Researchers want to conduct a natural history study to learn more about whether genetic factors can cause IBD; how immune cells contribute to IBD; and how diet, drugs, and disease affect those cells.

Objective:

To better understand IBD over time.

Eligibility:

Adults aged 18 to 85 years with Crohn's disease, ulcerative colitis, or another IBD. Their healthy relatives are also needed.

Design:

Affected participants will have clinic visits every 6 months for 3 years.

Once a year, they will have these procedures:

A physical exam with blood and stool samples.

Ultrasound of the abdomen. A wand will be rolled over the skin. It uses sound waves to capture images of the intestines.

Magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Magnetic fields will capture images of the intestines.

Colonoscopy. A long, flexible tube with a video camera will be inserted into the rectum to view the entire colon. Up to 12 tissue samples may be taken.

Upper endoscopy, for those with Crohn's disease. A long, thin tube with a camera will be inserted through the mouth and into the first part of the small intestine. Up to 12 small tissue samples may be taken.

Questionnaires. Participants will answer questions about their disease and their diet.

Midyear visits will include a physical exam, blood and stool collection, ultrasound, and questionnaires

Healthy relatives will have 1 blood draw for genetic tests.

Study Description:

This is a single-site, hypothesis-generating natural history study aiming to follow participants with inflammatory bowel disease. Participants will be followed long-term with a focus on immunophenotyping their conditions. Adult family members of participants will also be invited to enroll to provide blood samples for immune and genetic analyses.

Objectives:

Primary Objective: To collect longitudinal clinical data and specimens, with the goal of identifying novel biomarkers correlating with disease activity or response to therapy

Secondary Objectives:

1. To identify the dynamic molecular and immunological changes associated with chronic GI inflammation and mechanisms of response to FDA approved (biologic and small molecule inhibitors) therapies for IBD
2. To study the molecular genetics underlying chronic GI inflammation
3. To longitudinally quantify and characterize the nutritional status, food components, and overall diet of patients with IBD

Endpoints:

Primary Endpoint:

1. Longitudinal collection of clinical data, biospecimens, and disease assessments at 6-month intervals over at least 3 years

Secondary Endpoints:

1.A) Mean change over baseline of immune cell populations, cellular transcript and protein expression, and cytokine levels in peripheral blood and mucosal tissue across at least 3 study visits during a two-year period.

1.B) Assessment of disease activity (endoscopic evaluation, and histopathology) at each endoscopy and evaluation of progression of disease activity across at least 3 endoscopies during a two-year period. If a treatment is implemented, then disease activity will be assessed and compared over consecutive endoscopies.

1. C) Identification of molecular patterns or immune signatures that correlate with disease activity and response to treatment
2. A) Quantification of gene expression data and its trajectory over the course of disease and after therapy

2.B) Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype

3.A) To establish positive or negative correlations between specific food components and nutrient amounts with disease activity obtained from questionnaires over 12 months

3.B) to establish correlations with nutritional data and the microbiome over 12 months

• INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Affected Participant cohort:

1. Adults 18 - 85 years of age

2. History of:

   1. a verifiable diagnosis of Crohn's disease, ulcerative colitis, or IBD known to be associated with a co-existing condition (such as CTLA4 deficiency or common variable immune deficiency) and which is supported by characteristic clinical features, radiographic or endoscopic findings, or consistent histopathologic mucosal changes related to chronic inflammation; and/or
   2. a defined genetic syndrome/mutation linked to inflammatory bowel disease risk with or without symptoms or findings consistent with IBD

3. Presence of a referring community physician who would be able to manage care outside of NIH

Unaffected family member of participant:

Immediate relative to the enrolled participant (mother, father, sibling, or adult child) may be recruited and enrolled to improve interpretation of genetic results or expand the phenotype of the IBD

1. Adults 18 - 99 years of age
2. In good general health
3. No medical diagnosis of IBD

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Unable or unwilling to provide informed consent
2. Evidence of significant medical illnesses that the investigators feel may interfere with study evaluations and procedures

Patients with known or suspected inflammatory bowl disease