Identification/Characterization of Changes in Microscopic Colitis

Microscopic colitis (MC) is a chronic relapsing disease of the colon, characterized by watery
non-bloody diarrhea, usually normal colonoscopic findings, and typical histology findings. It
is frequently accompanied by abdominal pain, nocturnal diarrhea, and mild weight loss. The
incidence of MC has increased significantly over recent years with a 2010 study reporting
U.S. incidence for MC as 19.7 per 100,000 person-years. MC comprises two major histological
subtypes: collagenous colitis (CC), characterized by a distinctive thickened band of
subepithelial collagen (>10-20um), and lymphocytic colitis (LC), with an increased number of
intraepithelial lymphocytes (>20 lymphocytes per 100 epithelial cells).

Although the exact etiology of MC remains largely unknown, a few observational studies have
suggested associations with autoimmune disorders (e.g. celiac disease, and thyroid
disorders), cigarette smoking status, and medications such as non-steroidal anti-inflammatory
drugs (NSAIDS), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors
(SSRI), and statins. In addition to environmental factors, recently studies indicate that
genetics and specific infectious organisms may also play a role in development of the
disease. A recent study revealed a seasonal incidence pattern of lymphocytic colitis,
suggesting a potential link to an infectious or allergic component. Further, one study
demonstrated an association between collagenous colitis and persistent colonic C. difficile
infection. Additionally, while familial occurrence of MC has been reported, suggesting a
genetic predisposition, the roles of specific genetic factors have not been described.
Finally, recent studies demonstrate an association between MC and various autoimmune
disorders including celiac disease, autoimmune thyroid disease, and Sjören's syndrome,
indicating that MC may be part of a broader spectrum of autoimmune disorders. Despite these
findings, few studies have investigated the role of genetic, infectious, and immunological
factors in the development and progression of MC.

Budesonide is the only treatment for MC that appeared to be effective in randomized
controlled trials, with remission rates of 80%. However, recurrence of clinical symptoms
following withdrawal of treatment is not uncommon. Thus, further investigation of the
molecular mechanisms underlying MC is needed in order to obtain targeted and sustainable
treatment.

Analysis of clinical specimens obtained by colonoscopy from individuals affected with MC over
the course of their treatment offers a promising method by which to improve our understanding
of MC. Profiling of genetic and molecular characteristics such as changes in gut flora,
colonic mucosal immune profiles, and genetic factors over the course of treatment would
provide powerful insight into the role of these factors in the pathophysiology of the disease
which may ultimately lead to better treatments. Additionally, identification of disease
biomarkers can aid in developing disease monitoring and surveillance strategies.

Here, we propose to establish a cohort of individuals with suspected microscopic colitis
undergoing diagnostic colonoscopy at the Massachusetts General Hospital (MGH) to identify
genetic and molecular characteristics associated with the progression of this disease. This
study will elaborate on findings from a medical record review of patients with microscopic
colitis treated at MGH from 2002 to 2014. In addition to medical records, genetic and
molecular characteristics of colonic samples will be examined to determine their influence on
treatment response and outcomes.

Inclusion Criteria:

- Ability to give informed consent

- Ability and willingness to comply with all patient visits and study-related procedures

- Ability to understand and complete all study-related materials and questionnaires

- Patients ages 18 or older with suspected microscopic colitis

- Patients that have been previously treated for microscopic colitis that are being seen
for possible relapse will also be included

Exclusion Criteria:

- Inability to provide informed consent

- Inability or unwillingness to comply with all patient visits and study-related
procedures

- Inability to understand and complete all study-related materials and questionnaires

- Patients with a known diagnosis of Inflammatory Bowel Disease or colorectal cancer

- Patients with a known bleeding disorder, acute disease, or those that are awaiting
transplantation

- Patients who have taken antibiotics in the last two weeks

- Female subjects who are pregnant or nursing