Etiology Of Inflammatory Bowel Disease Research Articles

Tonsillectomy and the risk of inflammatory bowel disease: A systematic review and meta-analysis.

Tonsillectomy remains a controversial environmental factor in the etiology of inflammatory bowel disease (IBD). This meta-analysis aims to elucidate a more defined role of tonsillectomy in the development of IBD. Four databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science, were searched for studies exploring the association between tonsillectomy and the risk of IBD. The pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was assessed using chi-squared and I(2) statistical analysis. A funnel plot was performed to assess publication bias. A total of 23 observational studies involving 19 569 patients were included in our meta-analysis. Of these, 17 studies investigated the association between tonsillectomy and Crohn's disease (CD), and 22 studies explored its relationship with ulcerative colitis (UC). Overall, a positive relationship between tonsillectomy and development of CD (OR 1.37, 95% CI: 1.16-1.62) was observed, while there was no association between tonsillectomy and UC (OR 0.94, 95% CI: 0.84-1.05). When ORs were adjusted for smoking, the pooled OR for CD increased to 1.66 (95% CI: 1.03-2.68) and, for UC, changed to 1.03 (95% CI: 0.74-1.44). This meta-analysis demonstrates that tonsillectomy is associated with an increased risk of developing CD. We found no evidence to suggest that tonsillectomy exerts a protective effect on the development of UC, as is the case with appendectomy. Further prospective studies are required to confirm the validity of these observations.

Microbiome profiling of drinking water in relation to incidence of inflammatory bowel disease.

The etiology of inflammatory bowel disease (IBD) is unknown; current research is focused on determining environmental factors. One consideration is drinking water: water systems harbour considerable microbial diversity, with bacterial concentrations estimated at 10(6)-10(8) cells/L. Perhaps differences in microbial ecology of water sources may impact differential incidence rates of IBD. Regions of Manitoba were geographically mapped according to incidence rates of IBD and identified as high (HIA) or low (LIA) incidence areas. Bulk water, filter material, and pipe wall samples were collected from public buildings in different jurisdictions and their population structure analyzed using 16S rDNA sequencing. At the phylum level, Proteobacteria were observed significantly less frequently (P = 0.02) in HIA versus LIA. The abundance of Proteobacteria was also found to vary according to water treatment distribution networks. Gammaproteobacteria was the most abundant class of bacteria and was observed more frequently (P = 0.006) in LIA. At the genus level, microbes found to associate with HIA include Bradyrhizobium (P = 0.02) and Pseudomonas (P = 0.02). Particular microbes were found to associate with LIA or HIA, based on sample location and (or) type. This work lays out a basis for further studies exploring water as a potential environmental source for IBD triggers.

Current Understanding of Dysbiosis in Disease in Human and Animal Models.

Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases.

Whole Egg Consumption Increases Serum 25‐hydroxyvitamin D Concentrations in Rats with DSS‐Induced Colitis

The etiology of inflammatory bowel disease (IBD) is multifactorial. Some studies suggest that vitamin D deficiency has a role in both the development of IBD and disease severity. Moreover, it has also been shown that IBD results in a vitamin D deficient condition. Thus, the goal of this study was to evaluate the ability of a diet containing whole egg to maintain vitamin D balance in rats with dextran sodium sulfate (DSS)‐induced colitis. We hypothesized that because eggs are an excellent source of vitamin D, particularly 25‐(OH)‐vitamin D (25D), they represent a viable dietary strategy to maintain vitamin D balance during colitis development. In an initial dose response study, 5‐wk old Sprague‐Dawley rats (N=24) were randomly assigned to 4 groups (n=6 per group) of DSS‐treated drinking water (%, w/v): 0, 3, 4, and 5%. All rats were maintained on an AIN93 casein‐based diet for 5 wk. DSS‐treated drinking water replaced tap water for the final 7 d of the study period. Food and water were provided ad libitum. Prior to sacrifice, animals were placed in metabolism cages for 12 h for the collection of urine and to ensure they were in a fasted state. Urinary creatinine, 25D, and vitamin D binding protein (DBP), as well as serum 25D, were analyzed. Mean values were compared using a one‐way ANOVA (P< 0.05). Although urinary creatinine and 25D concentrations were not different across DSS groups, urinary DBP was significantly higher in the 3, 4 and 5% DSS groups compared to the 0% control (P= 0.025). Serum 25D concentrations exhibited a dose‐response with respect to DSS concentration and were significantly lower in the 4 and 5% DSS groups as compared to the 0 and 3% DSS‐treated rats. In a follow‐up study, rats (N=36) were randomly assigned to three diet groups (n=12 per group): a control AIN93 casein‐based diet, the same diet containing whole egg in place of casein, or a casein‐based diet with supplemented cholecalciferol (i.e., vitamin D3) at the same concentration (12.6 μg/kg diet) provided by the whole egg‐based diet. All diets were formulated to provide 20% (w/w) protein; thus, corn oil was added to the casein‐based diets to achieve the same total lipid content as the whole egg‐based diet. For the final 7 d of the 6 wk study, half of the rats in each diet group received 3.5% DSS drinking water. Control and DSS‐treated rats fed the whole egg‐based diet had serum 25D concentrations that were 61% higher than rats fed the casein‐based diets (P<0.001). Control casein‐fed rats supplemented with cholecalciferol had serum 25D concentrations that were 20% higher than control rats not receiving cholecalciferol supplementation (P= 0.009); however, cholecalciferol supplementation was without effect on serum 25D concentrations in DSS‐treated rats. These data strongly suggest that dietary consumption of whole egg results in: (1) an increase in serum 25D concentrations in control and IBD rats; and (2) increased serum 25D concentrations that were greater than an equivalent amount of supplemental cholecalciferol. Taken together, these results may support new dietary recommendations regarding whole egg consumption as a viable strategy for the management and/or prevention of vitamin D deficiency in IBD.Support or Funding InformationEgg Nutrition Center, Park Ridge, IL.

Is insulin-like growth factor 1 (IGF-1) system an attractive target inflammatory bowel diseases? Benefits and limitation of potential therapy.

Inflammatory bowel diseases (IBD) are chronic gastrointestinal disorders with unknown etiology, whose incidence dramatically increased over the past 50 years. Currently available strategies for IBD treatment, such as biological therapies, corticosteroids, and immunosuppressive agents are effective, but their side effects and economic costs cannot be ignored. Better understanding of IBD etiology and new therapeutics are thus needed. The aim of this paper is to briefly discuss IGF-1 dependent functions, with particular focus on IGF-1 use in IBD therapy. Data collection was based on records found in medical literature. Data analysis included records published between 1984 and 2014. The IGF-1 system is involved in major physiological functions, such as cell proliferation and metabolism, and growth promotion. Most importantly IGF-1 has anti-inflammatory properties and its use in IBD treatment can be recommended. However, potential IGF-1 therapy has some limitations, which include aggravation of fibrosis in Crohn's patients and facilitated transformation to malignancy. Taken into consideration their possible side effects, IGF-1 analogs and recombinants are nonetheless a promising target for IBD therapy for a specific group of patients. Further studies, at the clinical level are thus recommended.

Microbiome-Epigenome Interactions and the Environmental Origins of Inflammatory Bowel Diseases.

The incidence of pediatric inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, has risen alarmingly in the Western and developing world in recent decades. Epidemiologic (including monozygotic twin and migrant) studies highlight the substantial role of environment and nutrition in IBD etiology. Here we review the literature supporting the developmental and environmental origins hypothesis of IBD. We also provide a detailed exploration of how the human microbiome and epigenome (primarily through DNA methylation) may be important elements in the developmental origins of IBD in both children and adults.

Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease

The aetiology of inflammatory bowel disease (IBD) remains poorly understood. Recent evidence suggests an important role of gut microbial dysbiosis in IBD, and this may be associated with changes in faecal volatile organic metabolites (VOMs). To describe the changes in the faecal VOMs of patients with IBD and establish their diagnostic potential as non-invasive biomarkers. Faecal samples were obtained from 117 people with Crohn's disease (CD), 100 with ulcerative colitis (UC), and 109 healthy controls. Faecal VOMs were extracted using solid-phase micro-extraction and analysed by gas chromatography mass spectrometry. Data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profiles. The PLS-DA model showed clear separation of active CD from inactive disease and healthy controls (P < 0.001). Heptanal, 1-octen-3-ol, 2-piperidinone and 6-methyl-2-heptanone were up-regulated in the active CD group [variable important in projection (VIP) score 2.8, 2.7, 2.6 and 2.4, respectively], while methanethiol, 3-methyl-phenol, short-chain fatty acids and ester derivatives were found to be less abundant (VIP score of 3.5, 2.6, 1.5 and 1.2, respectively). The PLS-DA model also separated patients with small bowel CD from healthy controls and those with colonic CD from UC (P < 0.001). In contrast, less distinct separation was observed between active UC, inactive UC and healthy controls. Analysis of faecal volatile organic metabolites can provide an understanding of gut metabolomic changes in IBD. It has the potential to provide a non-invasive means of diagnosing IBD, and can differentiate between UC and CD.

The relationship between the immune system and oral manifestations of inflammatory bowel disease: a review

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory diseases characterized by exacerbations and remissions of the gastrointestinal tract, clinically manifested as Crohn’s disease and ulcerative colitis. The etiology of IBDs is considered to be multi factorial, comprising environmental, immune, microbial and genetic factors. Clinical signs may include abdominal pain, frequent bloody diarrheas, mucorrhea, vomiting, fever, fatigue or weight loss. Changes in the oral cavity often precede intestinal symptoms. Inflammatory bowel disease leads to a significant deterioration of oral health, which indicates that cooperation between the dentist and the gastroenterologist is necessary when considering patients’ welfare. Patients with IBD have an altered immune response, but microorganisms of the oral cavity may also be responsible for its modification.This review paper discusses the correlation between the immune system and inflammatory bowel disease manifestations in the oral cavity.

Application of computational methods in genetic study of inflammatory bowel disease.

Genetic factors play an important role in the etiology of inflammatory bowel disease (IBD). The launch of genome-wide association study (GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.

The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient's immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.

Changing epidemiological trends of inflammatory bowel disease in Asia.

Inflammatory bowel disease (IBD) has become more common in Asia over the past few decades. The rate of increase in prevalence of the disease varies greatly in Asia, with several countries in East Asia experiencing a more than doubled increase in IBD prevalence over the past decade. Historically, ulcerative colitis (UC) is more common than Crohn's disease (CD) in Asia. However, a reverse trend is beginning to appear in more developed countries in Asia such as Japan, Korea, and Hong Kong. While Asian IBD patients share many similarities with their Western counterparts, there are important differences with significant clinical implications. In Asia, there are more men with CD, more ileo-colonic involvement in CD, less familial aggregation, fewer extra-intestinal manifestations and worse clinical outcomes for older-onset patients with UC. These differences are likely related to the different genetic makeup and environmental exposures in different regions. Evaluation of the differences and rates in epidemiologic trends may help researchers and clinicians estimate disease burden and understand the reasons behind these differences, which may hold the key to unravel the etiology of IBD.

Mechanisms of Microbe-Host Interaction in Crohn's Disease: Dysbiosis vs. Pathobiont Selection.

Crohn’s disease (CD) is a systemic chronic inflammatory condition mainly characterized by discontinuous transmural pathology of the gastrointestinal tract and frequent extraintestinal manifestations with intermittent episodes of remission and relapse. Genome-wide association studies identified a number of risk loci that, catalyzed by environmental triggers, result in the loss of tolerance toward commensal bacteria based on dysregulated innate effector functions and antimicrobial defense, leading to exacerbated adaptive immune responses responsible for chronic immune-mediated tissue damage. In this review, we discuss the inter-related role of changes in the intestinal microbiota, epithelial barrier integrity, and immune cell functions on the pathogenesis of CD, describing the current approaches available to investigate the molecular mechanisms underlying the disease. Substantial effort has been dedicated to define disease-associated changes in the intestinal microbiota (dysbiosis) and to link pathobionts to the etiology of inflammatory bowel diseases. A cogent definition of dysbiosis is lacking, as well as an agreement of whether pathobionts or complex shifts in the microbiota trigger inflammation in the host. Among the rarely available animal models, SAMP/Yit and TNFdeltaARE mice are the best known displaying a transmural CD-like phenotype. New hypothesis-driven mouse models, e.g., epithelial-specific Caspase8−/−, ATG16L1−/−, and XBP1−/− mice, validate pathway-focused function of specific CD-associated risk genes highlighting the role of Paneth cells in antimicrobial defense. To study the causal role of bacteria in initiating inflammation in the host, the use of germ-free mouse models is indispensable. Unraveling the interactions of genes, immune cells and microbes constitute a criterion for the development of safe, reliable, and effective treatment options for CD.

Enterohepatic Helicobacter Species as a Potential Causative Factor in Inflammatory Bowel Disease: A Meta-Analysis.

The Helicobacter species in the gut microbiota comprise Helicobacter pylori (H pylori) and enterohepatic Helicobacter species (EHS), which can colonize the intestinal mucosa. However, it is unclear whether EHS are associated with inflammatory bowel disease (IBD). Therefore, we conducted this meta-analysis to examine the association between EHS and IBD.PubMed, Scopus, Cochrane Library, and Web of Science databases, as well as abstracts from conference proceedings were searched to identify studies that used polymerase chain reaction to detect Helicobacter species in intestinal samples from patients with IBD.After screening, we carefully reviewed 20 of the 2955 identified studies, and performed a meta-analysis of the findings from 14 studies (11 adult studies and 3 pediatric studies) using STATA v12.0. These studies evaluated 1407 individuals, including 433 patients with Crohn's disease, 306 patients with ulcerative colitis, and 668 controls. The prevalence of Helicobacter species was higher among the patients with IBD, compared to that among the controls, which corresponded to a pooled risk ratio (RR) of 1.59 (95% confidence interval [CI]: 1.12–2.27). The RRs for adult and pediatric patients with IBD were 1.61 (95% CI: 1.03–2.52) and 1.76 (95% CI: 1.17–2.64), respectively. Compared to the controls, the patients with IBD tended to have a higher prevalence of EHS in the intestinal mucosa (RR: 2.01, 95% CI: 1.36–2.98), although the prevalence of H pylori was not significantly higher (RR: 1.22, 95% CI: 0.77–1.95). Compared to the controls, the RRs for EHS in patients with Crohn's disease and ulcerative colitis were 1.72 (95% CI: 1.20–2.47) and 3.27 (95% CI: 0.93–11.44), respectively.It appears that EHS was associated with IBD, while intestinal H pylori infection was not significantly associated with IBD. Further studies are needed to determine the involvement of EHS in the microbiological etiology of IBD.

The Contribution of CD40/CD40L Axis in Inflammatory Bowel Disease: An Update.

Inflammatory bowel disease (IBD) is a chronic and multifactorial disease of the gastrointestinal tract. The exact etiology of IBD remains complex and unclear involving an inadequately defined relationship between microbial insult, genetic predisposition, altered intestinal barrier permeability, oxidative stress components and abnormal immune responses. The role of the co-stimulatory system made up of cluster of differentiation 40 protein (CD40) and its ligand (CD40L) in the response of the immune system to pathogens is now widely accepted. The implication of CD40/CD40L axis in immune system disorders due to its important role as signal transduction pathway among immune cells is well documented. Several studies have suggested that CD40/CD40L interactions regulate oxidative stress; this can affect various signaling pathways leading to IBD development. Hence, CD40/CD40L signaling pathway may become a new target for IBD treatment. This review will cover the general contribution of the CD40/CD40L dyad in the development of IBD in order to facilitate future approaches aiming to elucidate the immunological mechanisms that control gut inflammation.

Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease.

The diagnosis of inflammatory bowel disease (IBD) still remains a clinical challenge and the most accurate diagnostic procedure is a combination of clinical tests including invasive endoscopy. In this study we evaluated whether systematic miRNA expression profiling, in conjunction with machine learning techniques, is suitable as a non-invasive test for the major IBD phenotypes (Crohn's disease (CD) and ulcerative colitis (UC)). Based on microarray technology, expression levels of 863 miRNAs were determined for whole blood samples from 40 CD and 36 UC patients and compared to data from 38 healthy controls (HC). To further discriminate between disease-specific and general inflammation we included miRNA expression data from other inflammatory diseases (inflammation controls (IC): 24 chronic obstructive pulmonary disease (COPD), 23 multiple sclerosis, 38 pancreatitis and 45 sarcoidosis cases) as well as 70 healthy controls from previous studies. Classification problems considering 2, 3 or 4 groups were solved using different types of penalized support vector machines (SVMs). The resulting models were assessed regarding sparsity and performance and a subset was selected for further investigation. Measured by the area under the ROC curve (AUC) the corresponding median holdout-validated accuracy was estimated as ranging from 0.75 to 1.00 (including IC) and 0.89 to 0.98 (excluding IC), respectively. In combination, the corresponding models provide tools for the distinction of CD and UC as well as CD, UC and HC with expected classification error rates of 3.1 and 3.3%, respectively. These results were obtained by incorporating not more than 16 distinct miRNAs. Validated target genes of these miRNAs have been previously described as being related to IBD. For others we observed significant enrichment for IBD susceptibility loci identified in earlier GWAS. These results suggest that the proposed miRNA signature is of relevance for the etiology of IBD. Its diagnostic value, however, should be further evaluated in large, independent, clinically well characterized cohorts.

Epidemiología, seguimiento, monitorización y otros aspectos de la enfermedad inflamatoria intestinal

There are no important new data on the aetiology of inflammatory bowel disease. However, some new data were presented on the possible importance of certain nutrients or drugs in the genesis of the disease, as well as other data related to genetic features and their relationship with the microbiota. A highly interesting study suggested the strong potential of serological studies in predicting the course of Crohn's disease. The value of magnetic resonance imaging and the potential of low-radiation-dose tomography were reaffirmed in the monitoring and follow-up of patients and their treatments. Studies also confirmed the utility confirmed of new (and more comfortable) methods of home measurement of faecal calprotectin levels. In individualized therapy, attempts are being made to increase the practical application of new results on anti-TNF levels and their antibodies, for example, by identifying the utility of non-trough levels. We believe that the results presented on the impact of the disease on patients themselves were especially important, from their own perspective and in diverse setting. This impact is important both for patients (not only because of the repercussions of the disease on their quality of life but also on their mental health, disability, stress, and financial situation, etc.) and for their families. Finally, interesting results were presented of well-performed studies on colorectal cancer prevention in inflammatory bowel disease. These results confirm chromoendoscopy as a key technique but suggest that technological advances could change this situation, thus simplifying prevention.

The Enteric Virome in Inflammatory Bowel Disease

The Enteric Virome in Inflammatory Bowel Disease

Beneficial Effects of Probiotics, Prebiotics, Synbiotics, and Psychobiotics in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of diseases characterized by inflammation of the small and large intestine and primarily includes ulcerative colitis and Crohn's disease. Although the etiology of IBD is not fully understood, it is believed to result from the interaction of genetic, immunological, and environmental factors, including gut microbiota. Recent studies have shown a correlation between changes in the composition of the intestinal microbiota and IBD. Moreover, it has been suggested that probiotics and prebiotics influence the balance of beneficial and detrimental bacterial species, and thereby determine homeostasis versus inflammatory conditions. In this review, we focus on recent advances in the understanding of the role of prebiotics, probiotics, and synbiotics in functions of the gastrointestinal tract and the induction and maintenance of IBD remission. We also discuss the role of psychobiotics, which constitute a novel class of psychotropic agents that affect the central nervous system by influencing gut microbiota.

Lipidomic Profiling in Inflammatory Bowel Disease: Comparison Between Ulcerative Colitis and Crohn's Disease.

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is believed to be caused by abnormal host immune responses to the intestinal microbiome. However, the precise etiology of IBD remains unknown. Lipid metabolism and signaling are suggested to play important roles in inflammation with significant implications for IBD. In this study, we aimed to characterize lipidomic profiles in IBD with comparison between healthy controls, UC, and CD. Patients with IBD (n = 40, UC: 16 and CD: 24) and age- and gender-matched healthy volunteers (n = 84) were recruited. Plasma lipid profiles containing 333 lipid species were measured using electrospray ionization-tandem mass spectrometry. A total of 86 individual lipid species were significantly changed in CD compared with controls (78 decreased while 8 increased), with the majority belonging to the ether lipids including the alkylphospholipids (alkylphosphatidylcholine and alkylphosphatidylethanolamine) and plasmalogens (alkenylphosphatidylcholine and alkenylphosphatidylethanolamine). Of these 86 lipid species, 33 remained significantly and negatively associated with CD after adjusting for age, sex, waist circumference, current smoking, and diastolic blood pressure in logistic regression. In contrast, only 5 lipid species significantly differed between UC and controls. We demonstrate that a number of ether lipids (alkylphospholipid and plasmalogens) are significantly and negatively associated with CD. These alterations of lipid profiles particularly plasmalogens may contribute to the pathogenesis of IBD.

Luminal-GABA promotes inflammation in mouse models of colitis (MUC5P.756)

Abstract Background: Inflammatory bowel disease (IBD) results from a dysregulated immune response towards commensal microbiota. Although the etiology of IBD is unclear, there is considerable interest in the role of commensals and their metabolites in regulating pathology. Gamma-aminobutyric acid (GABA) is one metabolite produced by several commensal species that has been reported to have anti-inflammatory effects which could impact severity of IBD. Objective: To determine the physiological role of GABA on intestinal inflammation. Methods &amp; Results: C57BL/6 mice were administered GABA (2mg/ml) in their drinking water 3 days before induction of colitis (3% DSS or Clostridium difficile infection) and for another week thereafter. Intestinal tissue was collected and examined for histopathology, gene expression and cellular responses. In both models, administration of GABA exacerbated intestinal inflammation and damage, whereas inhibition of GABA with the receptor antagonist picrotoxin reduced disease severity. Damage was associated with increased expression of proinflammatory cytokines (IL-6 and IL-1β) and chemokines (CXCL1 and CXCL2) and alterations in macrophages and neutrophils. Conclusion: GABA increases host sensitivity to epithelial damage and inflammation. Identifying the effects of GABA on host immune defenses may reveal new approaches to treating and preventing IBD.