This F31 application is to investigate the mechanism by which alcohol exposure perpetuates the adverse symptoms associated with Ulcerative Colitis (UC), one of the two most common forms of Inflammatory Bowel Disease (IBD). Over 1.4 million Americans have been diagnosed with IBD, and UC makes up approximately half of those diagnoses. UC is cyclical, life-long disease where patients undergo periods of disease remission and active disease flares, which are characterized by symptoms of intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Currently, patients obtain symptomatic relief from an UC flare post flare onset as the precise trigger of an active UC flare from that of asymptomatic UC remission is not fully understood. A recent study reported that alcohol consumption results in worsening of the clinical symptoms associated with IBD and therefore `Don't Drink Alcohol' is a widespread recommendation to patients who are diagnosed with IBD/UC. However, the exact mechanism of how alcohol consumption exacerbates an UC flare has yet to be elucidated. We developed a novel mouse model of binge alcohol consumption following an induced colitis flare to study how alcohol consumption perpetuates UC. We found alcohol induced increases in both weight loss and colon shortening, both of which are well-documented symptoms in mouse models of UC flare. Just as increased weight loss and colon shortening are characteristic of an UC flare, increases in levels of the cytokine IL-22 are characteristic of entrance into an UC remission period. Using this model of alcohol consumption following induced colitis, we observed that mice exposed to alcohol following induced colitis were unable to mount proper colonic IL-22 responses. Thus, leading us to hypothesize that alcohol consumption impairs intestinal host defense mechanisms exacerbating active UC flares. The hypothesis will be tested in 3 aims using a well-established model of DSS-induced colitis with the novel adaptation of a binge alcohol paradigm.
Aim 1 will characterize the IL-22 response to binge alcohol consumption after DSS-induced colitis.
Aim 2 will determine whether gut barrier breakdown in DSS-colitis is further impaired with alcohol exposure.
Aim 3 will determine whether IL-22 normalizes gut barrier after DSS-colitis and binge alcohol exposure. Overall, we expect this study to illuminate potential translational contributions to the treatment and/or prevention of an alcohol induced UC flare.

Public Health Relevance

Patients presenting with Inflammatory Bowel Disease (IBD) are commonly told to not drink alcohol as it has previously correlated with IBD flare periods. The proposed studies will examine the mechanisms behind which alcohol use results in IBD flare, and thus may help in developing therapeutic strategies to maintain gut barrier integrity and protect from exacerbating symptoms associated with IBD.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZAA1)
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Jung, Kathy
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Loyola University Chicago
Schools of Medicine
United States
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Cannon, Abigail R; Kuprys, Paulius V; Cobb, Adrienne N et al. (2018) Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis. J Leukoc Biol 104:543-555
Hammer, Adam M; Morris, Niya L; Cannon, Abigail R et al. (2017) Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury. Shock 48:657-665
Li, Xiaoling; Cannon, Abigail R; Hammer, Adam M et al. (2017) IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-? in a mouse model of alcohol and burn injury. J Leukoc Biol 102:915-923