Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn’s disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.

The main environmental risk factor associated with the development of Crohn's disease (CD) is cigarette smoking. Although the mechanism is still unknown, some studies have shown that cigarette exposure affects the intestinal barrier of the small bowel. Among the factors that may be involved in this process are Paneth cells. These specialized epithelial cells are located into the small intestine, and they are able to secrete antimicrobial peptides, having an essential role in the control of the growth of microorganisms. Alterations in its function are associated with inflammatory processes, such as CD. To study how cigarette components impact ileum homeostasis and Paneth cells integrity, we used intragastric administration of cigarette smoke condensate (CSC) in mice. Our results showed that inflammation was triggered after mucosal exposure of CSC, which induced particular alterations in Paneth cells granules, antimicrobial peptide production, and a reduction of bactericidal capacity. In fact, exposure to CSC generated an imbalance in the fecal bacterial population and increased the susceptibility of mice to develop ileal damage in response to bacterial infection. Moreover, our results obtained in mice unable to produce interleukin 10 (IL-10^−/− mice) suggest that CSC treatment can induce a symptomatic enterocolitis with a pathological inflammation in genetically susceptible individuals.

Clostridium difficile infection (CDI) are the leading cause of world-wide nosocomial acquired diarrhea. The current main clinical challenge in CDI is the elevated rate of infection recurrence that may reach up to 30% of the patients, which has been associated to the formation of dormant spores during the infection. We sought to characterize the effects of oral administration of specific anti-spore IgY in mouse models of CDI and recurrent CDI. The specificity of anti-spore IgY was evaluated in vitro. In both, initiation mouse model and recurrence mouse model, we evaluated the prophylactic and therapeutic effect of anti-spore IgY, respectively. Our results demonstrate that anti-spore IgY exhibited high specificity and titers against C. difficile spores and reduced spore adherence to intestinal cells in vitro. Administration of anti-spore IgY to C57BL/6 mice prior and during CDI delayed the appearance of the diarrhea by 1.5 day, and spore adherence to the colonic mucosa by 90%. Notably, in the recurrence model, co-administration of anti-spore IgY coupled with vancomycin delayed the appearance of recurrent diarrhea by a median of 2 days. Collectively, these observations suggest that anti-spore IgY antibodies may be used as a novel prophylactic treatment for CDI, or in combination with antibiotics to treat CDI and prevent recurrence of the infection.

SUMMARY: In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.

Infectious diarrhea can be caused by a large number of microorganisms including bacteria virus and parasites. The clinical syndromic approach has been traditionally used to guide therapy. The aim of this study was to characterize the etiology of acute diarrhea by the FilmArray GI panel and to correlate it with its clinical presentation in an adult population presenting to the emergency room in a developing country. Material and Methods: Adult patients attending the ER due to acute diarrhea were selected. All patients included had a FilmArray GI panel performed and the clinical characteristics were recorded. Results: One hundred and ninety-nine patients were included. One hundred and eighteen (59.3%) were females. The mean age was 43 years old. Thirty three percent of the patients presented dysentery, 36.7% fever, 54.8% referred nauseas and 35.7% vomiting. Sixty three percent of the patients presented some degree of dehydration. In total, 221 microorganisms were detected of which 71.5% corresponded to bacteria (158/221), 19.9% to virus (44/221) and 8.6% to parasites (19/221). In 133 (67.0%) of 199 patients at least one microorganism was identified. Infections with more than one microorganism were detected in 27.1% of the patients. Polimicrobial infections were associated with a higher frequency of nausea (50.0% vs 32.0%, p 0.046), abdominal pain (87.0% vs 44.0%, p<0.0001) and travel history (20.0% vs 5.0%, p 0.0102). Bacterial infections occurred without a seasonal distribution with the exception of Salmonella sp whereas viral infections predominated during the autumn–winter months. Diarreicogenic E. coli were present in the context of a co-infection in more than 80.0% of the cases. Discussion: The use of multiplex panels has given us invaluable information regarding the epidemiology of acute diarrhea in adult. It highlighted the importance of polimicrobial infections and the frequency of diarreicogenic E. coli infections. Nevertheless, the lack of severity compared to monomicrobial infections and the usual association with other microorganisms in the latter make their clinical importance debatable.

Paneth cells (PCs) are specialized epithelial cells of the small bowel that contain multiple secretory granules filled with antimicrobial peptides and trophic factors, which are essential for the control of the microorganisms growth and maintaining intestinal integrity. Alterations in their function are associated with an imbalance of the normal microbiota, gastrointestinal infections and inflammatory processes, such as Crohn’s disease (CD). One of the most common murine models for studying CD is IL-10^-/- mouse. IL-10^-/- mice when housed in conventional conditions and take contact with commensal microorganisms develop an acute enterocolitis mediated by a Th1 immune response. Even though, alterations in PCs function are related to CD, they had not been characterized yet in this mouse model. Here we show that in specific pathogen free conditions IL-10^-/- mice have aberrant granules and a large number of immature PCs at the bottom of the crypt in the ileum of IL-10^-/- mice before developing intestinal inflammation, along with a reduced expression of Indian Hedgehog. In addition, IL-10^-/- Paneth cells presented a reduced expression of cryptidin-4, and a heterogeneous distribution of lysozyme+ granules. The alterations in the maturation of the PCs at the bottom of the crypt were not modified after the colonization by the conventional microbiota. On the other hand, depletion of microbiota altered the phenotype, but did not normalize PCs. Our results suggest that IL-10 could be necessary for the integrity of PCs. Moreover, our results help to explain why IL-10^-/- mice develop enterocolitis in response to microorganisms.