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The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (−55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction—both of which contribute to Na+ malabsorption and diarrhea. [ABSTRACT FROM AUTHOR]

Campylobacter concisus is an emerging pathogen associated with gastrointestinal disorders such as gastroenteritis and inflammatory bowel diseases ( IBD), but the species is also found in healthy subjects. The heterogeneous genome of C. concisus increases the likelihood of varying virulence between strains. Flagella motility is a crucial virulence factor for the well-recognized Campylobacter jejuni; therefore, this study aimed to analyze the motility of C. concisus isolated from saliva, gut biopsies, and feces of patients with IBD, gastroenteritis, and healthy subjects. The motility zones of 63 isolates from 52 patients were measured after microaerobic growth in soft-agar plates for 72 hours. The motility of C. concisus was significantly lower than that of Campylobacter jejuni and Campylobacter fetus subsp. fetus. The motility of C. concisus varied between isolates (4-22 mm), but there was no statistical significant difference between isolates from IBD patients and healthy subjects (p = 0.14). A tendency of a larger motility zones was observed for IBD gut mucosa isolates, although it did not reach statistical significance (p = 0.13), and no difference was found between oral or fecal isolates between groups. In conclusion, the varying motility of C. concisus could not be related to disease outcome or colonization sites. [ABSTRACT FROM AUTHOR]

The emerging enteric pathogen Campylobacter concisus is associated with prolonged diarrhea and inflammatory bowel disease. Previous studies have shown that C. concisus strains are very genetically diverse. Nevertheless, C. concisus strains have been divided into two genomospecies, where GS1 strains have been isolated predominantly from healthy individuals, while the GS2 cluster consists of isolates primarily from diarrheic individuals. The aim of the present study was to determine the genetic diversity of C. concisus isolates from Danish diarrheic patients. Multilocus sequence typing using the loci aspA, atpA, glnA, gltA, glyA, ilvD and pgm, as well as genomospecies based on specific differences in the 23S rRNA, was used to characterize 67 isolates (63 fecal and 4 oral), from 49 patients with different clinical presentations (29 with diarrhea, eight with bloody diarrhea, seven with collagenous colitis and five with Crohn's disease). MLST revealed a high diversity of C. concisus with 53 sequence types (STs), of which 52 were identified as 'new' STs. Allele sequences showed more than 90% similarity between isolates, with only four outliers. Dendrogram profiles of each allele showed a division into two groups, which more or less correlated with genomospecies A and genomospecies B. However, in contrary to previous results, this subgrouping had no association to the clinical severity of disease. [ABSTRACT FROM AUTHOR]

Background: Campylobacter concisus is a commensal of the human oral flora that has been linked to prolonged diarrhea and inflammatory bowel disease (IBD). It has been detected more often from intestinal biopsies in patients with IBD compared to healthy controls using PCR-based techniques, whereas the number of C. concisus culture-positive biopsies in previous studies has been very limited. Determining the rate of viable isolates present in the gut mucosa is of great importance when evaluating the role in different disease presentations. We therefore investigated a novel two-step cultivation procedure combining anaerobic and microaerobic incubation from several gut mucosal sites to improve isolate yield, and compared this to PCR results, from IBD patients and healthy controls. Results: Cultivation with the novel two-step procedure yielded a higher rate of C. concisus isolates from mucosal biopsies than previously reported by other methods. From 52 IBD patients, 52/245 (21%) biopsies were culture positive for C. concisus, while 121/245 (49%) of biopsies were PCR positive. For 26 healthy controls, the numbers were 23/182 (13%) and 66/182 (36%), respectively (p < 0.001). The rate of cultivation and PCR detection was higher for IBD patients compared to healthy controls (p = 0.021, p = 0.008, respectively). Conclusions: Patients with IBD had a higher prevalence of C. concisus than healthy controls, by both cultivation and PCR detection. We found a higher rate of C. concisus isolates from gut mucosal biopsies in both IBD patients and healthy controls than in preceding studies, indicating that colonization of C. concisus in the gastrointestinal tract is more extensive than previously assumed. [ABSTRACT FROM AUTHOR]

Limited information is available on the systemic immunoglobulin response in patients infected with the emerging pathogen Campylobacter concisus . The aim of the present study was to detect anti– C . concisus antibodies in serum of 88 patients with C . concisus gastroenteritis. Specific IgG antibodies to C . concisus were measured in serum using an in-house enzyme-linked immunosorbent assay, and pooled donor serum was used as a control. The mean optical density was 0.135 (SEM: 0.020) for the 88 adult patients and 0.100 (SEM: 0.011) in controls. When using an optical density value equal to the mean +3 SEM for the control serum, 22 (25%) C . concisus –positive patients had increased IgG antibodies. Patients with high IgG levels more often reported headache, and they had a trend toward more mucus in stools, whereas IgG levels were unrelated to age, duration of diarrhea, number of stools per day, and weight loss. [ABSTRACT FROM AUTHOR]

Campylobacter concisus is an emerging pathogen of the gastrointestinal tract that has been associated with Barrett's oesophagus, enteritis and inflammatory bowel disease. Despite having invasive potential in intestinal epithelial cells in-vitro, bacteraemic cases with C. concisus are extremely scarce, having only been reported once. Therefore, we conducted a serum resistance assay to investigate the bactericidal effects of human complement on C. concisus in comparison to some other Campylobacter species. In total, 22 Campylobacter strains were tested by incubation with normal human serum and subsequent cultivation in microaerobic conditions for 48 hours. Killing time was evaluated by decrease in total CFU over time for incubation with different serum concentrations. Faecal isolates of C. concisus showed inoculum reduction to less than 50% after 30 min. Campylobacter jejuni was sensitive to serum, but killing was delayed and a bacteraemic Campylobacter fetus subsp. fetus isolate was completely serum resistant. Interestingly, sensitivity of enteric C. concisus to human serum was not associated to different faecal-calprotectin levels. We find that faecal isolates of C. concisus are sensitive to the bactericidal effects of serum, which may explain why C. concisus is not associated to bacteraemia. [ABSTRACT FROM AUTHOR]

Objective. Gastroenteritis with Campylobacter concisus is an emerging infection, but the risk of irritable bowel syndrome (IBS) following it is unknown. Material and methods. In a prospective, community-based study of gastroenteritis with C. concisus and C. jejuni/coli, we invited adult patients to participate in a questionnaire study, including IBS symptoms and psychometric scores, at baseline and at 6 months. We estimated adjusted RR (RRadj) (for age, sex and comorbidity) for IBS as the primary outcome. Results. The development of IBS symptoms at 6 months was reported in 26/106 (25%) patients with C. concisus infection, and in 30/162 (19%) of C. jejuni/coli patients. The baseline predictors for IBS in C. concisus infection were high anxiety scores (RRadj 2.0; 95% CI 1.1-3.6, p < 0.05), chills (RRadj 1.9; 95% CI 1.0-3.6, p < 0.05), headache (RRadj 2.5; 95% CI 1.1-6.0, p < 0.05), dizziness (RRadj 2.6; 95% CI 1.2-5.8, p < 0.05) and muscle ache (RRadj 3.6; 95% CI 1.4-8.9, p < 0.01). For all Campylobacter patients ( n = 268), we confirmed previous reports of anxiety (RRadj 2.0; 95% CI 1.3-3.1), depression (RRadj 2.3; 95% CI 1.3-4.0) and high somatization scores (RRadj 3.0; 95% CI 1.5-6.0) as predictors for post-infectious IBS (PI-IBS). Conclusions. Gastroenteritis with C. concisus carries a 25% risk of IBS at 6-month follow-up. The risk factors for IBS are chills, headache, dizziness and muscle ache in the acute stage, as well as preexisting high psychometric scores for anxiety. Our findings suggest that psychological factors play a role in the development of PI-IBS. [ABSTRACT FROM AUTHOR]

Calprotectin (CP) is a calcium-binding cytosolic neutrophil protein and the concentration in feces reflects the migration of neutrophils into the gut lumen. Testing for fecal CP (f-CP) in patients with negative cultures for enteric pathogens is widely accepted as a useful screening tool for identifying patients who are most likely to benefit from endoscopy for suspected inflammatory bowel disease (IBD) with the assumption that a negative f-CP is compatible with a functional disorder. Campylobacter concisus has recently been reported to have a high incidence in the Danish population almost equal to Campylobacter jejuni and Campylobacter coli and has been reported to cause prolonged watery diarrhea. However, isolation of C. concisus from feces requires the filter method in a hydrogen-enriched microaerobic atmosphere, which is not commonly used in the laboratory, and the diagnosis may consequently be missed. The aim of this study was to evaluate the f-CP levels, as a marker for the intestinal inflammation in C. jejuni/coli- and C. concisus-infected patients. The authors found a high concentration of f-CP (median 631: IQR 221-1274) among 140 patients with C. jejuni/coli infection, whereas the f-CP level among 99 C. concisus-infected patients was significantly lower (median 53: IQR 20-169). The data correlate to the severe inflammatory gastroenteritis seen in patients infected with C. jejuni/coli, whereas C. concisus-infected patients have a much lower intestinal inflammation which could be compared with viral gastroenteritis. Nevertheless, clinicians should be aware of C. concisus infection, especially in patients with prolonged mild diarrhea, in the differential diagnosis to IBD. [ABSTRACT FROM AUTHOR]

A total of 5963 diarrheic stool samples were cultivated for Campylobacter spp. with use of modified charcoal cefoperazone deoxycholate agar (mCCDA) plates as well as a polycarbonate (PC) filter technique on blood agar plates. A total of 376 Campylobacter jejuni / coli were isolated from both PC and mCCDA. Six and three were isolated from PC and mCCDA only, respectively ( P = ns). The PC technique is noninferior to mCCDA for isolation of C. jejuni / coli . [ABSTRACT FROM AUTHOR]

Abstract: One thousand seven hundred ninety-one diarrheic stool samples were cultivated for Campylobacter spp. We found a high prevalence of Campylobacter concisus with use of a polycarbonate filter (n = 114) compared to a cellulose acetate filter (n = 79) (P < .0001). The polycarbonate filter is superior to the commonly used cellulose acetate filter for detection of C. concisus. [Copyright &y& Elsevier]