Phenotyping IBS: Perceptions and Modulations of Visceral Sensations

Despite recent breakthroughs in research, irritable bowel syndrome (IBS) lacks a comprehensive mechanistic characterization. While the symptoms of this gastroenterological disorder have been described, the overall assessment of IBS has not led to sufficient treatment and management plans. By moving away from an over-reliance on a symptom-based approach and shifting towards a mechanism-based approach, investigators will be more knowledgeable as they attempt to address the disease. In order to accomplish this, the investigators will work with different patient subgroups, specifically IBS subjects, healthy controls (HCs), and disease control groups such as ulcerative colitis (UC). This will allow for the comparison of significant genetic, social, biological, and neurological findings between subgroups, which will help investigators grasp the differences present in people who suffer from IBS.

The investigators will approach the study in a couple different ways to characterize IBS in the best possible manner. Blood samples and MRI brain images will be collected so that the genetic and neurological factors associated with IBS can be explored. Given the highly interactive nature of the biological systems within the body, the investigators plan to explore the interaction between the brain and the immune system as well as the brain and the gut. In doing so, specific genes that contribute to IBS, as well as changes in the brain that contribute to or result from IBS, can be further scrutinized.Additionally, the immune system's influence on the brain in IBS patients can be compared to healthy controls or UC. All of this information will contribute to therapeutic studies in the future as investigators continue to develop both diagnostic tools and treatments for IBS patients.

Conducting this study necessitates the use of human subjects for research purposes. In total, the investigators will recruit 120 IBS subjects, 70 age-matched HCs, and 100 UC subjects. During the initial screening visit, the subject will complete a physical examination, a short psychological evaluation (MINI+), a pressure & heat sensitivity test, a quick blood draw, and a set of questionnaires. In total, this baseline visit will take roughly two hours.

On the second visit, the subject will return to complete more questionnaires and have their brains scanned by an MRI machine. The subject will then be disclosed of MRI safety procedures and once they are cleared, they will undergo a 60 minute scanning session with a certified MRI technician. Once this has been complete, the subject will have completed the study.

IBS female subjects that have indicated they would like to be part of the longitudinal study will return at 3 months, 6 months, 9 months, and 12 months for the same MRI procedure described above, with MR-Spectroscopy being an additional modality. They will also complete a 5 minute online survey every month for 9 months to assess their symptoms.

The Neuroimaging Core at the Center for Neurobiology of Stress will be responsible for all brain imaging analyses in years 4-5. Gene expression profiling assays and all microbiome related studies will occur at the Neuroscience Genomics Core Laboratory and the UCLA Center for Systems Biomedicine in years 4-5 as well.

Inclusion criteria

for all IBS subjects:

• Meet Rome III criteria for IBS
• No red flag signs (i.e., weight loss, bloody stool, fever, anemia)

Inclusion criteria

for all UC subjects:

• Must have UC diagnosis that is clinically & histologically confirmed

Inclusion criteria

for all subjects:

• If woman of childbearing potential, must be willing to use contraception to avoid pregnancy during the course of the study
• If female, negative urine pregnancy tests at Screening & MRI Visit
• Willingness to participate in this study as evidenced by signed informed consent form
• ambulatory outpatient (does not depend on wheelchair for mobility)
• English is primary oral and written language

Exclusion criteria

for all subjects:

• Major medical intervention occurring in the next 6 months or in the past 6 months
• Presence of significant and ongoing medical problem interfering with participation
• Presence of major psychiatric diagnosis such as schizophrenia, bipolar disorder, PTSD, or Obsessive Compulsive disorder.
• Use of centrally acting medications that will interfere with neuroimaging testing (opiate analgesics, antidepressants).
• Left handed due to importance of laterality in neuroimaging
• Pregnancy or nursing
• Claustrophobia, Ferromagnetic Implants, or other problematic issues preventing subject participation in MRI
• Current or past history of chronic pain syndrome other than IBS in the IBS group
• History of gastrointestinal surgery other than uncomplicated appendectomy or cholecystectomy
• Use of investigational drugs, products, or devices within 28 days prior to screen and through study participation
• use of steroids in the last 6 months