Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study.

Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

¿Ha disminuido la colectomía por crisis de colitis ulcerosa?

Background: Treatment for moderate-severe active ulcerative colitis (UC) includes steroids, biologic therapy and total colectomy. Aim: To describe the features of patients with moderate to severe active UC, their hospital evolution and need for colectomy. Material and Methods: Non-concurrent cohort study of all patients admitted to our institution with a diagnosis of moderate or severe UC crisis between January 2008 and May 2019. Truelove Witts (TW) criteria were used to categorize disease severity. Twelve-month colectomy-free survival was estimated with Kaplan-Meier survival analysis. Results: One hundred-twenty patients aged 16 to 89 (median 35) years had 160 admissions for acute moderate to severe UC. Median admission per patient was 1 (1-3), and median hospital stay was six days (1-49). Cytomegalovirus and Clostridioides difficile were found in 17.5 and 14.2% of crises, respectively. Corticosteroids were used in all crises and biologic therapy in 6.9% of them. Emergency or elective colectomies were performed in 18.3 and 6.7% of patients, respectively. The need for emergency total colectomy decreased from 24.6 to 7.8% (Risk ratio 3.16, p < 0.01) between de first and second half of the study period. Kaplan-Meier analysis for long term colectomy-free survival in both periods confirmed this decrease (p < 0.01). Conclusions: Medical treatment for moderate to severe UC crises had a 86.3% success and a small percentage required emergency total colectomy. Emergency surgery decreased in the last decade.

Ethnicity influences phenotype and clinical outcomes: Comparing a South American with a North American inflammatory bowel disease cohort.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), has emerged as a global disease with an increasing incidence in developing and newly industrialized regions such as South America. This global rise offers the opportunity to explore the differences and similarities in disease presentation and outcomes across different genetic backgrounds and geographic locations. Our study includes 265 IBD patients. We performed an exploratory analysis of the databases of Chilean and North American IBD patients to compare the clinical phenotypes between the cohorts. We employed an unsupervised machine-learning approach using principal component analysis, uniform manifold approximation, and projection, among others, for each disease. Finally, we predicted the cohort (North American vs Chilean) using a random forest. Several unsupervised machine learning methods have separated the 2 main groups, supporting the differences between North American and Chilean patients with each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to the therapies and disease extension/location at diagnosis. Our random forest models were trained for cohort classification based on clinical characteristics, obtaining high accuracy (0.86 = UC; 0.79 = CD). Similarly, variables related to therapy and disease extension/location had a high Gini index. Similarly, univariate analysis showed a later CD age at diagnosis in Chilean IBD patients (37 vs 24; P = .005). Our study suggests a clinical difference between North American and Chilean IBD patients: later CD age at diagnosis with a predominantly less aggressive phenotype (39% vs 54% B1) and more limited disease, despite fewer biological therapies being used in Chile for both diseases.

Limited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection.

An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.

Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.

Origin, genomic diversity and microevolution of the Clostridium difficile B1/NAP1/RT027/ST01 strain in Costa Rica, Chile, Honduras and Mexico.

Clostridium difficile B1/NAP1/RT027/ST01 has been responsible for outbreaks of antibiotic-associated diarrhoea in clinical settings worldwide and is associated with severe disease presentations and increased mortality rates. Two fluoroquinolone-resistant (FQR) lineages of the epidemic B1/NAP1/RT027/ST01 strain emerged in the USA in the early 1990s and disseminated trans continentally (FQR1 and FQR2). However, it is unclear when and from where they entered Latin America (LA) and whether isolates from LA exhibit unique genomic features when compared to B1/NAP1/RT027/ST01 isolates from other regions of the world. To answer the first issue we compared whole-genome sequences (WGS) of 25 clinical isolates typed as NAP1, RT027 or ST01 in Costa Rica (n=16), Chile (n=5), Honduras (n=3) and Mexico (n=1) to WGS of 129 global isolates from the same genotype using Bayesian phylogenomics. The second question was addressed through a detailed analysis of the number and type of mutations of the LA isolates and their mobile resistome. All but two B1/NAP1/RT027/ST01 isolates from LA belong to the FQR2 lineage (n=23, 92 %), confirming its widespread distribution. As indicated by analysis of a dataset composed of 154 WGS, the B1/NAP1/RT027/ST01 strain was introduced into the four LA countries analysed between 1998 and 2005 from North America (twice) and Europe (at least four times). These events occurred soon after the emergence of the FQR lineages and more than one decade before the first report of the detection of the B1/NAP1/RT027/ST01 in LA. A total of 552 SNPs were identified across all genomes examined (3.8-4.3 Mb) in pairwise comparisons to the R20291 reference genome. Moreover, pairwise SNP distances were among the smallest distances determined in this species so far (0 to 55). Despite this high level of genomic conservation, 39 unique SNPs (7 %) in genes that play roles in the infection process (i.e. slpA) or antibiotic resistance (i.e. rpoB, fusA) distinguished the LA isolates. In addition, isolates from Chile, Honduras and Mexico had twice as many antibiotic resistance genes (ARGs, n=4) than related isolates from other regions. Their unique set of ARGs includes a cfr-like gene and tetM, which were found as part of putative mobile genetic elements whose sequences resemble undescribed integrative and conjugative elements. These results show multiple, independent introductions of B1/NAP1/RT027/ST01 isolates from the FQR1 and FQR2 lineages from different geographical sources into LA and a rather rapid accumulation of distinct mutations and acquired ARG by the LA isolates.

Do Patients Older Than 60 Years With Inflammatory Bowel Disease Have More Vertebral Fractures Than Age-matched Controls? A Study Using Abdominal and Pelvic CT Scans With Sagittal Reformatting as Screening Tool.

INTRODUCTION: It is undetermined whether patients with inflammatory bowel diseases (IBDs) have increased prevalence of vertebral compression fractures (VCFs) since many VCFs are asymptomatic and radiographs may overlook them. We compared the prevalence of VCFs in patients older than 60 years with and without IBDs. METHODS: We studied 55 patients with IBDs and 165 controls who underwent CT scans for nonspinal conditions. We evaluated the presence of VCFs, fracture severity using the Genant score, and we determined whether age, sex, diagnosis of IBD, treatment, and time since diagnosis were associated with VCFs. Using logistic regression analysis, we assessed the independent effect of each variable. RESULTS: Mean age was 72.7 years; 165 patients (75%) were women. Thirty-five patients (16%) had at least one VCF (16.4% IBD; 15.8% controls, P = 0.92); both groups exhibited similar fracture severity. Patients with VCFs were older than patients without VCFs (79.8 versus 70.2, P < 0.01 IBD; 76.4 versus 72.4, P = 0.02 controls). No other clinical variables were different in patients with and without VCFs in either cohort. Only age was independently associated with VCFs in both cohorts. DISCUSSION: VCFs were not more frequent or severe in patients older than 60 years with IBD presented than in age-matched controls.

[Experience of continuing online education in gastroenterology for non specialist medical doctors]. / Experiencia de educación continua en línea en gastroenterología para médicos no especialistas.

BACKGROUND: Continuing education is essential for health professions and online courses can be a good way for professional development. AIM: To describe the experience with online courses for continuing education in hepatology and gastroenterology and to analyze their educational impact. MATERIAL AND METHODS: A three years' experience in courses on liver diseases and digestive tract is described. Their curricular design, methodology, and the educational impact was analyzed using the four levels of the Kirkpatrick's model. RESULTS: On average, there were 321 students per course (2015-2017). 94% were Chilean and 6% from abroad (20 countries). In the educational impact analysis, in level 1 "reaction": 93% said that the course fulfilled their expectations and 92% would recommend it. In level 2 "learning": 42% approved the courses. Level 3 "behavior" was not evaluated and level 4 "organizational change" highlighted that the traditional face-to-face continuing education model of Chilean Gastroenterology Society (SChG) changed to full distance model in these three courses, with 1284 students from South America, Asia and Europe, in a 3-years-period. Additionally, these programs were included in the Medical Society of Santiago (SMS) continuing education agenda. CONCLUSIONS: The alliance between the SMS and the SChG generated on line courses that meet the educational needs of physicians and medical students, with excellent results and student perception.

Mucosal Exposure to Cigarette Components Induces Intestinal Inflammation and Alters Antimicrobial Response in Mice.

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.

The absence of interleukin 10 affects the morphology, differentiation, granule content and the production of cryptidin-4 in Paneth cells in mice.

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.

Experiencia de educación continua en línea en gastroenterología para médicos no especialistas / Experience of continuing online education in gastroenterology for non specialist medical doctors

Background: Continuing education is essential for health professions and online courses can be a good way for professional development. Aim: To describe the experience with online courses for continuing education in hepatology and gastroenterology and to analyze their educational impact. Material and Methods: A three years' experience in courses on liver diseases and digestive tract is described. Their curricular design, methodology, and the educational impact was analyzed using the four levels of the Kirkpatrick's model. Results: On average, there were 321 students per course (2015-2017). 94% were Chilean and 6% from abroad (20 countries). In the educational impact analysis, in level 1 "reaction": 93% said that the course fulfilled their expectations and 92% would recommend it. In level 2 "learning": 42% approved the courses. Level 3 "behavior" was not evaluated and level 4 "organizational change" highlighted that the traditional face-to-face continuing education model of Chilean Gastroenterology Society (SChG) changed to full distance model in these three courses, with 1284 students from South America, Asia and Europe, in a 3-years-period. Additionally, these programs were included in the Medical Society of Santiago (SMS) continuing education agenda. Conclusions: The alliance between the SMS and the SChG generated on line courses that meet the educational needs of physicians and medical students, with excellent results and student perception.

Etiologic and clinical characterization of community acquired gastroenteritis in adult patients in a Chilean emergency room by the FilmArray GI panel.

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.

Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression.

Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

[Outcome of surgery for Crohn's colitis. Review of 28 cases]. / Colitis de Crohn: resultados del tratamiento quirúrgico y evolución alejada.

BACKGROUND: Exclusive involvement of the colon or rectum in Crohn's disease, called Crohn's colitis, (CC) occurs in about 25% of these patients. AIM: To analyze early surgical results and long-term outcomes of patients undergoing surgery for CC. MATERIAL AND METHODS: Review of a prospective database, identifying patients with Crohn's disease operated between 2003 and 2015 and excluding those with ileocecal disease. We analyzed demographic data, pre and postoperative pharmacological treatment, operations, morbidity and the need for a second bowel resection at follow-up. RESULTS: We reviewed data from 28 patients aged 17 to 72 years (15 men). Twenty-seven (96.4%) had previous pharmacological treatment, 11 received monoclonal antibodies. The most common indications for surgical treatment were failure of medical treatment in 15 cases, acute severe colitis in 12 and anemia/malnutrition in eight. Total colectomy was performed in 17 (61%) patients, proctocolectomy in 8 (29%) and segmental colectomies in 3 (11%). Sixteen (57%) were operated laparoscopically. Major postoperative complications were observed in 5 (18%). Four needed a reintervention. There was no operative mortality. During a 55 months median follow-up of 27 patients, seven (26%) required a second bowel resection, one of them for recurrence. Nineteen (70%) patients had an ostomy, which was permanent in 11. Fifteen patients are without medical treatment. CONCLUSIONS: Most of the reviewed patients required total colectomy for the control of the disease with a low surgical morbidity. Two-thirds required an ileostomy, which became permanent in half of them.

Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation.

Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium) infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS) and interleukin (IL)-10-/- mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10-/- mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2). Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10-/- mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

Impact of Cigarette Smoking on the Gastrointestinal Tract Inflammation: Opposing Effects in Crohn's Disease and Ulcerative Colitis.

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.