Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis

Abstract

Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Interestingly, a widespread recommendation to IBD patients for avoidance of a flare period is "Don't Drink Alcohol" as recent work correlated alcohol consumption with increased GI symptoms in patients with IBD. Alcohol alone not only induces a systemic pro-inflammatory response, but can also be directly harmful to gut barrier integrity. However, how alcohol could result in the exacerbation of UC in both patients and murine models of colitis has yet to be elucidated. Therefore, we conducted a retrospective analysis of patients admitted for IBD with a documented history of alcohol use in conjunction with a newly developed mouse model of binge alcohol consumption following dextran sulfate sodium (DSS)-induced colitis. We found that alcohol negatively impacts clinical outcomes of patients with IBD, specifically increased intestinal infections, antibiotic injections, abdomen CT scans, and large intestine biopsies. Furthermore, in our mouse model of binge alcohol consumption following an induced colitis flare, we found alcohol exacerbates weight loss, clinical scores, colonic shortening and inflammation, and propensity to infection. These findings highlight alcohol's ability to potentiate symptoms and susceptibility to infection in UC and suggest alcohol as an underlying factor in perpetuating symptoms of IBD.

Alcohol decreases intestinal ratio of Lactobacillus to Enterobacteriaceae and induces hepatic immune tolerance in a murine model of DSS-colitis

“…Consistent with our previous observations, 9 mice gavaged with alcohol after DSS treatment shows more pronounced weight loss and shorter colon lengths ( Figure S1a-c). To assess intestinal bacterial changes, cecal contents, and colon contents were harvested from mice euthanized on experimental day seven, 3 h after final gavage.…”

“…These bacterial changes may in part explain our previously observed finding that ethanol exacerbates colitis flare. 9 Barrier function was similarly compromised between the mice receiving DSS+Vehicle and DSS+Ethanol, however, circulating endotoxin levels were higher in the DSS +Ethanol mice. The circulating endotoxin can initiate liver inflammation, which we observed as increased liver triglycerides, mononuclear cell infiltrate, and ALT levels in the DSS+Ethanol mice.…”

“…51 The limited effects of ethanol alone are further underscored by the limited changes in the mucins of this study and the intestinal pathology noted in this study and our previous study. 9 Due to the association of lactobacilli with gut health, numerous studies have turned to the reintroduction of these bacteria in the setting of colitis, [52][53][54][55] and alcohol consumption. 13,18,56,57 One beneficial effect of lactobacilli is their ability to limit the proliferative of Enterobacteriaceae and other pathogenic bacteria.…”

“…The mouse model used in this study was previously described. 9 Briefly, mice were randomly assigned to four experimental groups: Control+Vehicle (Ctrl+V), Control+Ethanol (Ctrl+E), Dextran sodium sulfate+Vehicle (DSS+V), Dextran sodium sulfate+Ethanol (DSS+E). Mice were administered either normal drinking water or a 2% (w/v) solution of DSS (36,000-50,000 molecular weight; MP Biomedicals) ad libitum, starting on day 0 and until day 5.…”

“…Studies examining IBD patients have found that alcohol consumption is associated with worsening of gastrointestinal symptoms, 6,7 induction of flare, 8 and increased intestinal infections. 9 These effects may arise from alcohol's ability to alter the intestinal microbiota, [10][11][12][13][14] which would negatively impact the already altered intestinal microbiome of IBD patients. [15][16][17] In particular, alcohol consumption and IBD are independently characterized by intestinal decreases of the Lactobacillus genus, 18,19 and increases of the Enterobacteriaceae family.…”