• Epigenetic
• Inflammatory bowel disease (IBD)
• N6-methyladenosine (m(6)A)

• Animals
• Humans
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/pathology
• Epigenesis, Genetic
• Genetic Predisposition to Disease
• Immune System
• Methylation
• Mammals

• Crohn’s disease
• Enterohepatic circulation
• FXR
• GPBAR1
• Gut barrier
• Gut microbiota
• Nuclear receptors
• Ulcerative colitis

• Humans
• Bile Acids and Salts/metabolism
• Liver/pathology
• Inflammation
• Inflammatory Bowel Diseases/etiology
• Microbiota

• 722619 Horizon 2020
• 734719 Horizon 2020
• H99C20000340002 Regione Puglia
• EUROSEEDS Uniba - S56 Universita degli Studi di Bari Aldo Moro
• Università degli Studi di Bari Aldo Moro

• brain
• central and enteral nervous systems
• inflammatory bowel disease
• oxidative and nitrosative stress in inflammatory bowel disease

• Crohn’s disease
• Functional variants
• Genes
• Inflammatory bowel disease
• Mutations

• Computational Biology
• Crohn Disease/diagnosis
• Genome-Wide Association Study
• Humans
• Inflammatory Bowel Diseases

The small intestine is a digestive organ that has a complex and dynamic ecosystem, which is vulnerable to the risk of pathogen infections and disorders or imbalances. Many studies have focused attention on intestinal mechanisms, such as host–microbiome interactions and pathways, which are associated with its healthy and diseased conditions. This review highlights the intestine models currently used for simulating such normal and diseased states. We introduce the typical models used to simulate the intestine along with its cell composition, structure, cellular functions, and external environment and review the current state of the art for in vitro cell-based models of the small intestine system to replace animal models, including ex vivo, 2D culture, organoid, lab-on-a-chip, and 3D culture models. These models are described in terms of their structure, composition, and co-culture availability with microbiomes. Furthermore, we discuss the potential application for the aforementioned techniques to these in vitro models. The review concludes with a summary of intestine models from the viewpoint of current techniques as well as their main features, highlighting potential future developments and applications.

• 3D culture
• disease model
• ex vivo model
• host-microbiome interaction
• in vitro model
• intestinal glycans
• small intestine

• Crohn's disease
• enteric infection
• inflammatory bowel disease
• meta-analysis
• ulcerative colitis

Cigarette smoke (CS) has adverse effects in patients with Crohn’s disease (CD), an inflammatory bowel disease (IBD) that has been associated with microbial infection, immuno-dysregulation, and mucosal dysfunction. However, CS seems to provide relief and protection to patients with another IBD known as ulcerative colitis (UC). These two subsets are featured as M1- and M2-mediated responses, respectively. Nicotine is the most active, addictive, and studied ingredient in CS. The mechanism of how nicotine and/or other CS ingredients induce pro-inflammatory or anti-inflammatory phenotypes in IBD patients remains under investigation. Our most recent in vitro nicotine study provided significant insights toward understanding the contradictory effects of nicotine on IBD patients, and it elucidated the mechanistic role of α7nAChR in modulation of macrophages in tobacco smokers. Shifting the beneficial effect of nicotine to a harmful outcome in CD patients was linked to a nicotine-microbe interaction that supports a microbial etiology in CD pathogenesis. Among the most debated pathogens in CD etiology is Mycobacterium avium subspecies paratuberculosis (MAP). Other studies associated nicotine with upregulation of miR-124 expression in macrophages, which led to anti-inflammatory response. This review discusses published work on the role of nicotine in modulation of the innate immune response and subsequent signaling in macrophages in IBD subsets.

• Crohn’s disease
• MAP
• macrophage
• miR-124
• nicotine
• ulcerative colitis
• α7nAChR

Inflammatory bowel disease (IBD) has become a global disease with accelerating incidence worldwide in the 21st century while its accurate etiology remains unclear. In the past decade, gut microbiota dysbiosis has consistently been associated with IBD. Although many IBD-associated dysbiosis have not been proven to be a cause or an effect of IBD, it is often hypothesized that at least some of alteration in microbiome is protective or causative. In this article, we selectively reviewed the hypothesis supported by both association studies in human and pathogenesis studies in biological models. Specifically, we reviewed the potential protective bacterial pathways and species against IBD, as well as the potential causative bacterial pathways and species of IBD. We also reviewed the potential roles of some members of mycobiome and virome in IBD. Lastly, we covered the current status of therapeutic approaches targeting microbiome, which is a promising strategy to alleviate and cure this inflammatory disease.

• dysbiosis
• etiology
• inflammatory bowel disease
• microbiome
• pathogenesis
• therapy

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that promote ligand-dependent transcription of target genes that regulate energy production, lipid metabolism, and inflammation. The PPAR superfamily comprises three subtypes, PPARα, PPARγ, and PPARβ/δ, with differential tissue distributions. In addition to their different roles in the regulation of energy balance and carbohydrate and lipid metabolism, an emerging function of PPARs includes normal homeostasis of intestinal tissue. PPARα activation represses NF-κB signaling, which decreases the inflammatory cytokine production by different cell types, while PPARγ ligands can inhibit activation of macrophages and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Il-1β. In this regard, the anti-inflammatory responses induced by PPAR activation might restore physiopathological imbalances associated with inflammatory bowel diseases (IBD). Thus, PPARs and their ligands have important therapeutic potential. This review briefly discusses the roles of PPARs in the physiopathology and therapies of the most important IBDs, ulcerative colitis (UC), and Crohn's disease (CD), as well some new experimental compounds with PPAR activity as promising drugs for IBD treatment.

• Crohn's disease
• PPARα
• PPARβ/δ
• PPARγ
• inflammatory bowel diseases
• ulcerative colitis

There are various etiologies of colonic injury and inflammation. The most commonly described colitides in clinical practice are associated with infection, inflammatory bowel disease, ischemia, radiation and medications. The colonic wall has a limited set of responses to different types of injury; therefore, there is overlap between many of these disorders. Focal active colitis is characterized by isolated neutrophilic cryptitis with the background mucosa displaying normal crypt architecture. This inflammatory pattern can be easily unnoticed by pathologists because on low-power examination the mucosa may have almost normal appearance. General practitioners also may not be familiar with this term, underlying etiologies, associated risk factors, course, available therapies and follow up. 

We present a case of an 82-year-old female with chronic diarrhea and weight loss. She had a negative infectious workup and normal radiology series. She subsequently underwent endoscopic evaluation in lieu of persistent and debilitating symptoms which revealed nonspecific macroscopic findings with pathology noting focal active colitis. She was empirically treated with a 14-day course of Xifaxan and responded well to management with almost complete resolution of her symptoms and no recurrence on six-month follow-up.

• chronic diarrhea
• cryptitis
• focal active colitis
• infectious colitis
• inflammatory bowel disease.
• irritable bowel syndrome
• xifaxan

• Animals
• Colitis/chemically induced
• Colitis/drug therapy
• Colitis/pathology
• Colon/drug effects
• Colon/pathology
• Colon/physiology
• Dextran Sulfate/toxicity
• Down-Regulation/drug effects
• Female
• Heme Oxygenase-1/genetics
• Heme Oxygenase-1/metabolism
• Imidazolidines/pharmacology
• Interleukin-10/blood
• Interleukin-10/genetics
• Interleukin-10/metabolism
• Kelch-Like ECH-Associated Protein 1/metabolism
• Larva/chemistry
• Larva/metabolism
• Lipopolysaccharides/toxicity
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2/antagonists & inhibitors
• NF-E2-Related Factor 2/metabolism
• Oxidative Stress/drug effects
• Plant Extracts/chemistry
• Plant Extracts/pharmacology
• RAW 264.7 Cells
• Spiro Compounds/pharmacology
• Superoxide Dismutase/metabolism
• Tumor Necrosis Factor-alpha/blood
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism

• Crohn’s disease
• endoscopic recurrence
• metronidazole

• Adult
• Anastomosis, Surgical
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/therapeutic use
• Case-Control Studies
• Crohn Disease/drug therapy
• Crohn Disease/prevention & control
• Crohn Disease/surgery
• Crohn Disease/therapy
• Female
• Humans
• Ileum/surgery
• Male
• Metronidazole/administration & dosage
• Metronidazole/therapeutic use
• Middle Aged
• Recurrence
• Retrospective Studies
• Risk Factors
• Secondary Prevention/methods
• Young Adult

• P30 DK042086 NIDDK NIH HHS

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

• fecal microbiota transplantation (FMT)
• gut microbiota
• inflammatory bowel disease
• pathogenesis
• prebiotics
• probiotics
• synbiotics

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.

• Salmonella enterica serovar Typhimurium
• colitis
• dextran sulfate sodium
• inflammatory bowel disease
• interleukin-10
• persistence

• Johne's disease
• Mycobacterium avium subsp. paratuberculosis
• disease
• food
• pathogen
• public health
• review
• zoonotic

• Adolescent
• Age Factors
• Case-Control Studies
• Child
• Child, Preschool
• Crohn Disease/epidemiology
• Crohn Disease/etiology
• Environmental Exposure
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Risk Factors
• South Africa/epidemiology

• P30 DK097948 NIDDK NIH HHS
• T32 DK083251 NIDDK NIH HHS

• Bacteria/pathogenicity
• Crohn Disease/microbiology
• Crohn Disease/pathology
• Dysbiosis
• Host-Pathogen Interactions
• Humans

• Crohn’s disease
• Escherichia coli
• Faecalibacterium prausnitzii
• Psoriasis
• gastrointestinal microbiome
• hidradenitis suppurativa
• inflammatory bowel diseases
• microbiota
• skin diseases
• skin manifestations
• ulcerative colitis

• clostridium difficile infection
• crohn’s disease
• chronic antibiotic

• Endoscopy
• Inflammatory bowel disease
• Serologic markers

• Antibodies, Antineutrophil Cytoplasmic/metabolism
• Antibodies, Bacterial/metabolism
• Biomarkers/metabolism
• Endoscopy, Gastrointestinal
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/metabolism

• Adherent-invasive Escherichia coli (AIEC)
• IS900, fimH gene
• Inflammatory bowel disease
• Mycobacterium avium subsp. paratuberculosis (MAP)

• Adult
• Aged
• Bacteremia
• Coinfection
• DNA, Bacterial
• Escherichia coli/genetics
• Escherichia coli Infections/complications
• Escherichia coli Infections/epidemiology
• Female
• Genes, Bacterial
• Humans
• Inflammatory Bowel Diseases/complications
• Male
• Middle Aged
• Mycobacterium avium subsp. paratuberculosis/genetics
• Paratuberculosis/complications
• Paratuberculosis/epidemiology
• Prevalence
• Prospective Studies
• Young Adult

• BACTERIAL TRANSLOCATION
• CROHN'S DISEASE
• MOLECULAR BIOLOGY
• RIBOSOMAL RNA
• SURGICAL RESECTION

• autoimmunity
• gastrointestinal immune response
• infectious disease
• inflammatory bowel disease

• Adult
• Aged
• Antigens, Viral/analysis
• Case-Control Studies
• Colitis, Ulcerative/immunology
• Computational Biology
• Crohn Disease/immunology
• Diagnosis, Differential
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Measles virus/immunology
• Middle Aged

• Colitis
• Helminth-derived molecules
• Helminths
• Inflammatory bowel disease
• Innate and adaptive immunity
• Therapy

• Animals
• Clinical Trials as Topic
• Disease Models, Animal
• Humans
• Immune System Diseases/immunology
• Immune System Diseases/therapy
• Immunomodulation/immunology
• Inflammation Mediators/metabolism
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/therapy
• Therapy with Helminths/methods

AIM: To study the association between exposure to Salmonella enterica (SE) and Crohn’s disease (CD) and its clinical implications in Chilean patients.

METHODS: Ninety-four unrelated Chilean CD patients from CAREI (Active Cohort Registry of Inflammatory Bowel Disease) presenting to a single inflammatory bowel disease (IBD) unit of a University Hospital were prospectively included in this study. A complete clinical evaluation, including smoking history, was performed at the initial visit, and all the important data of clinical evolution of CD were obtained. Blood samples from these CD patients and 88 healthy sex- and age-matched control subjects were analyzed for exposure to SE and for their NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide antibodies [immunoglobulin-G type (IgG)] and polymerase chain reaction (PCR), respectively. We also evaluated exposure to SE in 90 sex- and age-matched patients without CD, but with known smoking status (30 smokers, 30 non-smokers, and 30 former smokers).

RESULTS: CD patients comprised 54 females and 40 males, aged 35.5 ± 15.2 years at diagnosis with a mean follow-up of 9.0 ± 6.8 years. CD was inflammatory in 59 patients (62.7%), stricturing in 24 (25.5%) and penetrating in 15 (15.5%). Thirty cases (31.9%) had lesions in the ileum, 29 (30.8%) had ileocolonic lesions, 32 (34.0%) had colonic lesions and 23 (24.4%) had perianal disease. Sixteen CD patients (17%) were exposed to SE compared to 15 (17%) of 88 healthy control subjects (P = 0.8). Thirty-one CD patients (32.9%) were smokers, and 7 (7.4%) were former smokers at diagnosis. In the group exposed to SE, 10 of 16 patients (62.5%) were active smokers compared to 21 of 78 patients (26.9%) in the unexposed group (P = 0.01). On the other hand, 10 of 31 smoking patients (32%) were exposed to SE compared to 5 of 56 nonsmoking patients (9%), and one of the seven former smokers (14%) (P = 0.01). In the group of 90 patients without CD, but whose smoking status was known, there was no difference in exposure to SE [3 of 30 smokers (10%), 5 of 30 non-smokers (16%), and 5 of 30 former smokers (16%); P = 0.6]. There were no differences in disease severity between CD patients with and those without anti-SE IgG antibodies, estimated as the appearance of stricturing [2 (12.5%) vs 22 (28.2%); P = 0.2] or penetrating lesions [2 (12.5%) vs 13 (16.6%); P = 1.0]; or the need for immunosuppressants [11 (68.7%) vs 55 (70.5%); P = 1.0], anti-tumor necrosis factor therapy [1 (6.2%) vs 7 (8.9%); P = 1.0], hospitalization [13 (81.2%) vs 58 (74.3%); P = 0.7], or surgery [3 (18.7%) vs 12 (15.3%); P = 0.3), respectively]. No other factors were associated with SE, including NOD2/CARD15 gene status. Seventeen CD patients (18%) had at least one mutation of the NOD2/CARD15 gene.

CONCLUSION: Our study found no association between exposure to SE and CD. We observed a positive correlation between SE exposure and cigarette smoking in Chilean patients with CD, but not with disease severity.

• Crohn’s disease
• Salmonella
• Infection
• Tobacco
• Smoking
• Environmental factors

• Adult
• Antibodies, Bacterial/blood
• Biomarkers/blood
• Case-Control Studies
• Chile/epidemiology
• Crohn Disease/diagnosis
• Crohn Disease/epidemiology
• Crohn Disease/genetics
• Crohn Disease/microbiology
• Female
• Humans
• Male
• Middle Aged
• Nod2 Signaling Adaptor Protein/genetics
• Registries
• Risk Factors
• Salmonella Infections/diagnosis
• Salmonella Infections/epidemiology
• Salmonella Infections/microbiology
• Salmonella Infections/therapy
• Salmonella enterica/immunology
• Salmonella enterica/pathogenicity
• Severity of Illness Index
• Smoking/adverse effects
• Smoking/epidemiology
• Young Adult

• Bilophila/isolation & purification
• Clostridium/physiology
• Crohn Disease/microbiology
• Female
• Gastrointestinal Tract/microbiology
• Humans
• Male
• Metagenome

Many data coming from animal models and clinical observations support an involvement of intestinal microbiota in the pathogenesis of Crohn’s disease (CD). It is hypothesized in fact, that the development of chronic intestinal inflammation is caused by an abnormal immune response to normal flora in genetically susceptible hosts. The involvement of bacteria in CD inflammation has provided the rationale for including antibiotics in the therapeutic armamentarium. However, randomized controlled trials have failed to demonstrate an efficacy of these drugs in patients with active uncomplicated CD, even if a subgroup of patients with colonic location seems to get benefit from antibiotics. Nitroimidazole compounds have been shown to be efficacious in decreasing CD recurrence rates in operated patients, and the use of metronidazole and ciprofloxacin is recommended in perianal disease. However, the appearance of systemic side effects limits antibiotic long-term employment necessary for treating a chronic relapsing disease. Rifaximin, characterized by an excellent safety profile, has provided promising results in inducing remission of CD.

• Antibiotics
• Crohn’s disease
• Gut microbiota
• Mycobacteria

• inflammatory bowel disease
• crohn’s disease (cd)
• ulcerative colitis (uc)
• anti-glycan
• serological biomarkers
• meta-analysis
• systemic review
• disease complication
• surgery for ibd

• Humans
• Antibodies, Anti-Idiotypic/blood
• Biomarkers/blood
• Case-Control Studies
• Disease Progression
• Inflammatory Bowel Diseases/blood
• Inflammatory Bowel Diseases/diagnosis
• Polysaccharides/antagonists & inhibitors
• Polysaccharides/immunology
• Prognosis

• R21 DK077064 NIDDK NIH HHS
• R21 DK077064-02 NIDDK NIH HHS
• R21 DK077064-02S1 NIDDK NIH HHS
• R21 DK077064-02S2 NIDDK NIH HHS

• Adult
• Antigen-Antibody Reactions
• Bacterial Proteins/chemistry
• Bacterial Proteins/immunology
• Connexins/blood
• Connexins/chemistry
• Connexins/immunology
• Crohn Disease/blood
• Crohn Disease/immunology
• Crohn Disease/microbiology
• Enterovirus B, Human/chemistry
• Enterovirus C, Human/chemistry
• Female
• Humans
• Lactococcus lactis/chemistry
• Male
• Middle Aged
• Molecular Mimicry/immunology
• Sequence Homology, Amino Acid
• Viral Proteins/chemistry
• Viral Proteins/immunology
• Gap Junction alpha-4 Protein

• deformation
• migration
• enterocyte
• signaling

• Animals
• Cell Line
• Focal Adhesion Protein-Tyrosine Kinases/genetics
• Focal Adhesion Protein-Tyrosine Kinases/metabolism
• Humans
• Intestinal Mucosa/enzymology
• Mutation
• Myosin Light Chains/metabolism
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors/metabolism
• Protein Serine-Threonine Kinases/antagonists & inhibitors
• Protein Serine-Threonine Kinases/physiology
• Proto-Oncogene Proteins c-akt/metabolism
• Pyrimidines/administration & dosage
• RNA, Small Interfering/physiology
• Rats
• Wound Healing
• src-Family Kinases/antagonists & inhibitors

• R01 DK067257 NIDDK NIH HHS
• R01 DK-067257 NIDDK NIH HHS

Crohn's disease (CD) is a high morbidity chronic inflammatory disorder of unknown aetiology. Adherent-invasive Escherichia coli (AIEC) has been recently implicated in the origin and perpetuation of CD. Because bacterial biofilms in the gut mucosa are suspected to play a role in CD and biofilm formation is a feature of certain pathogenic E. coli strains, we compared the biofilm formation capacity of 27 AIEC and 38 non-AIEC strains isolated from the intestinal mucosa. Biofilm formation capacity was then contrasted with the AIEC phenotype, the serotype, the phylotype, and the presence of virulence genes.

Specific biofilm formation (SBF) indices were higher amongst AIEC than non-AIEC strains (P = 0.012). In addition, 65.4% of moderate to strong biofilms producers were AIEC, whereas 74.4% of weak biofilm producers were non-AIEC (P = 0.002). These data indicate that AIEC strains were more efficient biofilm producers than non-AIEC strains. Moreover, adhesion (P = 0.009) and invasion (P = 0.003) indices correlated positively with higher SBF indices. Additionally, motility (100%, P < 0.001), H1 type flagellin (53.8%, P < 0.001), serogroups O83 (19.2%, P = 0.008) and O22 (26.9%, P = 0.001), the presence of virulence genes such as sfa/focDE (38.5%, P = 0.003) and ibeA (26.9%, P = 0.017), and B2 phylotype (80.8%, P < 0.001) were frequent characteristics amongst biofilm producers.

The principal contribution of the present work is the finding that biofilm formation capacity is a novel, complementary pathogenic feature of the recently described AIEC pathovar. Characterization of AIEC specific genetic determinants, and the regulatory pathways, involved in biofilm formation will likely bring new insights into AIEC pathogenesis.

Recent studies suggest potential roles of the endocannabinoid system in gastrointestinal inflammation. Although cannabinoid CB₂ receptor expression is increased in inflammatory disorders, the presence and function of the remaining proteins of the endocannabinoid system in the colonic tissue is not well characterized.

Cannabinoid CB₁ and CB₂ receptors, the enzymes for endocannabinoid biosynthesis DAGLα, DAGLβ and NAPE-PLD, and the endocannabinoid-degradating enzymes FAAH and MAGL were analysed in both acute untreated active ulcerative pancolitis and treated quiescent patients in comparison with healthy human colonic tissue by immunocytochemistry. Analyses were carried out according to clinical criteria, taking into account the severity at onset and treatment received.

Western blot and immunocytochemistry indicated that the endocannabinoid system is present in the colonic tissue, but it shows a differential distribution in epithelium, lamina propria, smooth muscle and enteric plexi. Quantification of epithelial immunoreactivity showed an increase of CB₂ receptor, DAGLα and MAGL expression, mainly in mild and moderate pancolitis patients. In contrast, NAPE-PLD expression decreased in moderate and severe pancolitis patients. During quiescent pancolitis, CB₁, CB₂ and DAGLα expression dropped, while NAPE-PLD expression rose, mainly in patients treated with 5-ASA or 5-ASA+corticosteroids. The number of immune cells containing MAGL and FAAH in the lamina propria increased in acute pancolitis patients, but dropped after treatment.

Endocannabinoids signaling pathway, through CB₂ receptor, may reduce colitis-associated inflammation suggesting a potential drugable target for the treatment of inflammatory bowel diseases.

• strain
• pressure
• gastrointestinal
• signaling
• tensegrity
• integrins

• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Gastrointestinal Neoplasms/metabolism
• Gastrointestinal Neoplasms/pathology
• Humans
• Integrins/metabolism
• Intestinal Mucosa/metabolism
• Mechanotransduction, Cellular
• Stress, Mechanical

• R01 DK060771 NIDDK NIH HHS
• R01 DK067257 NIDDK NIH HHS
• T32 GM008420 NIGMS NIH HHS
• 2 T32 GM008420 NIGMS NIH HHS