Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease.

Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

BACKGROUND: The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS: This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS: One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS: HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.

Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.

A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.

Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients.

BACKGROUND: Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS: We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS: FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS: Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.

Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission.

BACKGROUND: Consensus regarding the cutoff value of fecal calprotectin (FC) for predicting histological healing (HH) in ulcerative colitis (UC) is lacking. This study aimed to determine an optimal FC cutoff value for predicting HH in patients with UC with clinical and endoscopic remission. Furthermore, FC's predictability for prolonged clinical remission (CR) was investigated. METHODS: Patients with UC in clinical and endoscopic remission, defined as a partial Mayo score (PMS) ≤ 2 points and a Mayo endoscopic subscore 0-1, were prospectively enrolled. Biopsy samples were evaluated by Geboes score (GS), with HH defined as a GS < 2.0. Patients were followed for 2 years or until relapse, defined as a PMS > 2 or medication escalation. RESULTS: Seventy-six patients with UC were included. The median FC value in patients with HH (n = 40) was 56.2 µg/g, significantly lower than that in those with histological activity (118.1 µg/g; P < .01). The area under the curve (AUC) in a receiver operating characteristic (ROC) curve analysis to predict HH for FC was 0.71 (95% confidence interval [CI], 0.59-0.83), with an optimal cutoff value of 82.7 µg/g (73% sensitivity; 64% specificity; P < .01). Of 74 patients observed for 2 years, 54 (73%) had prolonged CR. In the ROC curve analysis, the AUC to predict prolonged CR for FC was 0.79 (95% CI, 0.68-0.90), equivalent to that for HH (0.73; 95% CI, 0.64-0.86; P = .40). The optimal FC cutoff value to predict prolonged CR was 84.6 µg/g (72% sensitivity; 85% specificity; P < .01). CONCLUSIONS: Fecal calprotectin < 82 µg/g predicts HH in patients with UC with clinical and endoscopic remission. Low FC leads to prolonged CR, equivalent to HH.

Fecal calprotectin (FC) levels < 82 µg/g predict histological healing in ulcerative colitis patients with clinical and endoscopic remission. Low FC leads to prolonged clinical remission for up to 2 years in those with clinical and endoscopic remission, equivalent to histological healing.

KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients.

Along with a recent remarkable decrease in Helicobacter pylori-infected individuals, reports of gastric neoplasms such as sporadic foveolar-type gastric adenoma (FGA) in H. pylori-naive patients have been increasing. This tumor, with its raspberry-like appearance, is common in H. pylori-naive gastric mucosa. The current study investigated the genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori-naive patients were subjected to whole genome analysis using a next-generation sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial cells, along with plasmid transfection of candidate variants, were examined. A mean of 6.65 × 108 total reads were obtained for each sample. Common genetic abnormalities in well-known proliferation driver genes of conventional gastric dysplasia/cancer were not found. However, a common single-nucleotide variation (SNV) was noted within the DNA-binding domain of the tumor suppressor gene KLF4. This novel SNV was located in the zinc finger 2 region. Additional experiments showed that it significantly suppressed proliferation of gastric epithelial cells compared with wild-type KLF4 plasmid-transfected cells, although suppression was reduced in early apoptotic phase-related genes. A novel SNV in the KLF4 zinc finger 2 region was commonly found in sporadic FGA tissue samples, which may explain the slow-growing properties of this neoplasm.

Mucosal metabolites fuel the growth and virulence of E. coli linked to Crohn's disease.

Elucidating how resident enteric bacteria interact with their hosts to promote health or inflammation is of central importance to diarrheal and inflammatory bowel diseases across species. Here, we integrated the microbial and chemical microenvironment of a patient's ileal mucosa with their clinical phenotype and genotype to identify factors favoring the growth and virulence of adherent and invasive E. coli (AIEC) linked to Crohn's disease. We determined that the ileal niche of AIEC was characterized by inflammation, dysbiosis, coculture of Enterococcus, and oxidative stress. We discovered that mucosal metabolites supported general growth of ileal E. coli, with a selective effect of ethanolamine on AIEC that was augmented by cometabolism of ileitis-associated amino acids and glutathione and by symbiosis-associated fucose. This metabolic plasticity was facilitated by the eut and pdu microcompartments, amino acid metabolism, γ-glutamyl-cycle, and pleiotropic stress responses. We linked metabolism to virulence and found that ethanolamine and glutamine enhanced AIEC motility, infectivity, and proinflammatory responses in vitro. We connected use of ethanolamine to intestinal inflammation and L-fuculose phosphate aldolase (fucA) to symbiosis in AIEC monoassociated IL10-/- mice. Collectively, we established that AIEC were pathoadapted to utilize mucosal metabolites associated with health and inflammation for growth and virulence, enabling the transition from symbiont to pathogen in a susceptible host.

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

A New Dawn for the Use of Artificial Intelligence in Gastroenterology, Hepatology and Pancreatology.

Artificial intelligence (AI) is rapidly becoming an essential tool in the medical field as well as in daily life. Recent developments in deep learning, a subfield of AI, have brought remarkable advances in image recognition, which facilitates improvement in the early detection of cancer by endoscopy, ultrasonography, and computed tomography. In addition, AI-assisted big data analysis represents a great step forward for precision medicine. This review provides an overview of AI technology, particularly for gastroenterology, hepatology, and pancreatology, to help clinicians utilize AI in the near future.

Primary Extragastrointestinal Stromal Tumor of Greater Omentum with Intraperitoneal Bleeding.

Gastrointestinal stromal tumors (GISTs) develop in the digestive tract, mainly in the stomach, small intestine, colon, or esophagus. However, primary tumors with the same pathologic features as GISTs have been reported to occur outside of the digestive tract and are called extragastrointestinal stromal tumor (EGIST). We herein report a rare case of EGIST arising from the greater omentum in a patient with abdominal pain caused by intraperitoneal bleeding from the tumor.

Detection and Quantification of Transforming Growth Factor-ß1 Produced by Murine B Cells: Pros and Cons of Different Techniques.

Transforming growth factor (TGF)-ß1 is one of the regulatory cytokines produced by B cells and has a pivotal role in intestinal homeostasis. TGF-ß1 can determine the fate of naive T cells, such as differentiation, proliferation, and apoptosis, which are relevant to the pathogenesis of autoimmunity, infection, inflammation, allergy, and cancer. Here, we describe detailed methods for detection and quantification of TGF-ß1 secreted by B cells using ELISA, flow cytometry, and real-time PCR.

Intermittent Purpura Development Associated with Leukocytoclastic Vasculitis Induced by Infliximab for Crohn's Disease.

Anti-tumor necrosis factor (TNF) α agents, widely used for the treatment of Crohn's disease (CD), can sometimes induce skin-associated adverse events, which mainly include psoriasis-like eruptions, eczema, and cutaneous infections. In contrast, purpura caused by vasculitis is rarely seen. We herein report a unique case of leukocytoclastic vasculitis induced by infliximab administered for CD in which intermittent purpura development was noted. Fluorescent immunostaining showed no immunoglobulin A deposition on the vessel walls. No purpura was initially seen after starting infliximab, but it appeared approximately 10 months later; however, administration did not have to be discontinued, and the condition was later resolved. The present findings provide important details regarding vasculitis induced by anti-tumor necrosis factor-α agent administration.

Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.

Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.

Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type.

Fecal calprotectin level in ulcerative colitis patients is correlated with endoscopic findings. However, its association with various ulcerative colitis disease types has not been elucidated. In the present study, we investigated the correlation of fecal calprotectin level with endoscopic findings as compared to blood biomarkers according to ulcerative colitis disease type. Fecal calprotectin as well as the blood biomarkers: C-reactive protein (CRP), white blood count (WBC), erythrocyte sedimentation rate (ESR), hemoglobin, platelet count (PLT), and serum albumin (Alb) were measured in patients who underwent a complete colonoscopy. Disease type was divided into proctitis, left-sided colitis, and extensive colitis. Correlations of fecal calprotectin and blood biomarker levels with Mayo endoscopic subscore were analyzed. A total of 186 colonoscopy examinations were performed in 124 patients with ulcerative colitis. Fecal calprotectin level showed a significant correlation with Mayo endoscopic subscore regardless of disease type (proctitis, r = 0.54, p<0.01; left-sided colitis, r = 0.75, p<0.01; extensive colitis, r = 0.78, p<0.01), and clearly discriminated inactive (Mayo endoscopic subscore 0) from active stages (Mayo endoscopic subscore 1-3). On the other hand, none of the examined blood biomarkers showed a correlation with Mayo endoscopic subscore in the proctitis group, while weak correlations of several biomarkers (CRP, WBC, ESR, PLT and Alb) with Mayo endoscopic subscore were found in left-sided colitis and extensive colitis cases. This is the first report to elucidate the capabilities of fecal calprotectin and blood biomarkers as endoscopic surrogate markers according to ulcerative colitis disease type.

Serum amyloid A level correlated with endoscopic findings in patients with Crohn's disease-Possible biomarker for evaluating mucosal healing.

BACKGROUND: Mucosal healing (MH) has been proposed as an essential therapeutic goal for treatment of Crohn's disease (CD) patients. The utility of serum amyloid A (SAA) for prediction of MH in CD patients is lacking. AIMS: This study was conducted to evaluate the correlation of SAA with CD-related endoscopic disease activity. METHODS: SAA levels in serum samples obtained from CD patients as well as endoscopic findings based on a simple endoscopic score for CD (SES-CD) were assessed in relation to CD activity index (CDAI). The diagnostic ability of MH in correlation with SAA level was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-five patients with CD were enrolled. Mean SAA level was significantly higher in clinical and endoscopic active phases as compared to an inactive phase. SAA level was also significantly correlated with SES-CD (r = 0.64, p < 0.01) and CDAI (r = 0.42, p < 0.01). The area under the ROC curve for SAA level was 0.77 and the optimal cut-off value for SAA to predict MH was 5.9 µg/dl. SAA level was shown to be associated with MH, with a sensitivity of 68% and specificity of 83%. CONCLUSIONS: SAA may be a possible biomarker for evaluating MH in CD patients.

Celiac disease in non-clinical populations of Japan.

BACKGROUND: Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease. METHODS: Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests. RESULTS: Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings. CONCLUSION: The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms.

Fecal Calprotectin More Accurately Predicts Endoscopic Remission of Crohn's Disease than Serological Biomarkers Evaluated Using Balloon-assisted Enteroscopy.

BACKGROUND: Fecal calprotectin (FC) has emerged as a reliable surrogate marker of endoscopic remission in Crohn's disease (CD), which has been mainly evaluated using ileocolonoscopy. We conducted this study to clarify the predictability of FC level for predicting endoscopic remission using balloon-assisted enteroscopy (BAE) findings in patients with CD and compare with that of conventional serological biomarkers. METHODS: Patients with CD scheduled to undergo BAE were prospectively enrolled, and fecal and blood samples collected before the procedures. We used a modified simple endoscopic score for CD, in which the parameter "presence of narrowing" was removed from conventional simple endoscopic score for CD. Endoscopic remission was defined as modified simple endoscopic score for CD 0 to 2. RESULTS: Seventy BAE procedures were performed in 53 patients with CD and evaluated. The area under the curve in receiver operating characteristic curve analysis of FC to predict endoscopic remission was 0.93, with an optimal cut-off value of 252.9 µg/g, and 96% sensitivity and 83% specificity, which was higher than that for C-reactive protein, albumin, white blood cell count, and platelet count (0.76, 0.66, 0.39, and 0.65, respectively). The area under the curve of FC for predicting endoscopic remission was high in patients with ileal and ileocolonic disease location (0.86 and 0.96, cut-off values 204.2 and 253.7 µg/g, respectively), and also higher than the area under the curve values of serological markers. CONCLUSIONS: BAE findings showed that FC was more accurate for predicting endoscopic remission in CD than C-reactive protein, albumin, white blood cell count, and platelet count. Even in small-bowel CD, FC may be a more reliable surrogate marker of endoscopic remission than serological biomarkers.

Fecal calprotectin level correlated with both endoscopic severity and disease extent in ulcerative colitis.

BACKGROUND: The relationship between fecal calprotectin (FC) and disease extent in ulcerative colitis (UC) has not been fully elucidated. The aim of this study was to clarify the correlation of FC with disease extent and severity in UC patients. METHODS: UC patients scheduled to undergo an ileocolonoscopy were enrolled and fecal samples for FC measurement were collected prior to the procedure. A Mayo endoscopic subscore (MES) was determined for each of 5 colonic segments. To evaluate the association of FC with extent of affected mucosa as well as disease severity, we assessed the correlation of FC level with the sum of MES (S-MES) for the 5 colonic segments as compared to the maximum score of MES (M-MES). RESULTS: FC measurements in conjunction with findings from 136 complete colonoscopies in 102 UC patients were evaluated. FC level showed a stronger correlation with S-MES (correlation coefficient r = 0.86, p < 0.001) as compared to M-MES (r = 0.79, p < 0.001). In patients with an M-MES of 1, 2, and 3, FC level showed a significant correlation with S-MES (r = 0.67, p < 0.001; r = 0.70, p < 0.001; r = 0.47, p = 0.04, respectively). Our findings indicate that FC level is elevated in patients with greater areas of affected mucosa even in those with the same M-MES value. CONCLUSIONS: FC level was shown to be correlated with the extent of affected mucosa as well as severity in UC patients, thus it is useful for precise assessment of mucosal inflammation.

Primary Pancreatic Malignant Lymphoma Diagnosed from Endoscopic Ultrasound-guided Fine-needle Aspiration Findings.

A 60-year-old woman was admitted to our hospital with upper abdominal pain and jaundice. Computed tomography showed a 9-cm mass that was penetrated by the common hepatic artery in the pancreatic head area. Endoscopic retrograde pancreatography revealed no stenosis or obstruction of the main pancreatic duct, and a cytologic examination of the patient's pancreatic juice was negative. Next, endoscopic ultrasound-guided fine needle aspiration was performed. The immunohistological findings of the specimen revealed a diffuse large B-cell lymphoma. The size of the tumor was significantly reduced after 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone).

Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

BACKGROUND: CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood. METHODS: We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with acute or chronic dextran sulfate sodium (DSS)-induced colonic injury were examined, and the frequency of colonic LP CD5+ B cells in those was assessed by flow cytometry. RESULTS: The expression level of TLR9 was higher in colonic LP CD5+ B cells as compared to CD5- B cells. Colonic LP CD5+ B cells produced greater amounts of IL-10 following stimulation with TLR ligands, especially TLR9, as compared with the LP CD5- B cells. Acute intestinal inflammation transiently decreased the frequency of colonic LP CD5+ B cells, while chronic inflammation induced a persistent decrease in colonic LP CD5+ B cells and led to a CD5- B cell-dominant condition. CONCLUSION: A persistent altered mucosal B cell population caused by chronic gut inflammation may be involved in the pathogenesis of inflammatory bowel diseases.