The Host Cellular Immune Response to Infection by Campylobacter Spp. and Its Role in Disease.

Campylobacter spp. are the leading cause of bacterium-derived gastroenteritis worldwide, impacting 96 million individuals annually. Unlike other bacterial pathogens of the gastrointestinal tract, Campylobacter spp. lack many of the classical virulence factors that are often associated with the ability to induce disease in humans, including an array of canonical secretion systems and toxins. Consequently, the clinical manifestations of human campylobacteriosis and its resulting gastrointestinal pathology are believed to be primarily due to the host immune response toward the bacterium. Further, while gastrointestinal infection is usually self-limiting, numerous postinfectious disorders can occur, including the development of Guillain-Barré syndrome, reactive arthritis, and irritable bowel syndrome. Because gastrointestinal disease likely results from the host immune response, the development of these postinfectious disorders may be due to dysregulation or misdirection of the same inflammatory response. As a result, it is becoming increasingly important to the Campylobacter field, and human health, that the cellular immune responses toward Campylobacter be better understood, including which immunological events are critical to the development of disease and the postinfectious disorders mentioned above. In this review, we collectively cover the cellular immune responses across susceptible hosts to Campylobacter jejuni infection, along with the tissue pathology and postinfectious disorders which may develop.

Immune-Mediated Aggravation of the Campylobacter concisus-Induced Epithelial Barrier Dysfunction.

Campylobacter concisus is a human-pathogenic bacterium of the gastrointestinal tract. This study aimed at the contribution of the mucosal immune system in the context of intestinal epithelial barrier dysfunction induced by C. concisus. As an experimental leaky gut model, we used in vitro co-cultures of colonic epithelial cell monolayers (HT-29/B6-GR/MR) with M1-macrophage-like THP-1 cells on the basal side. Forty-eight hours after C. concisus infection, the decrease in the transepithelial electrical resistance in cell monolayers was more pronounced in co-culture condition and 22 ± 2% (p < 0.001) higher than the monoculture condition without THP-1 cells. Concomitantly, we observed a reduction in the expression of the tight junction proteins occludin and tricellulin. We also detected a profound increase in 4 kDa FITC-dextran permeability in C. concisus-infected cell monolayers only in co-culture conditions. This is explained by loss of tricellulin from tricellular tight junctions (tTJs) after C. concisus infection. As an underlying mechanism, we observed an inflammatory response after C. concisus infection through pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) released from THP-1 cells in the co-culture condition. In conclusion, the activation of subepithelial immune cells exacerbates colonic epithelial barrier dysfunction by C. concisus through tricellulin disruption in tTJs, leading to increased antigen permeability (leaky gut concept).

Development of an enzyme-linked immunosorbent assay for detecting Campylobacter hepaticus specific antibodies in chicken sera - a key tool in Spotty Liver Disease screening and vaccine development.

Spotty Liver Disease (SLD) is an emerging disease of serious concern in the egg production industry, as it causes significant egg loss and mortality in layer hens. The causative agent is a newly identified Gram-negative bacterium, Campylobacter hepaticus, and knowledge about C. hepaticus pathogenesis and the potential for vaccine development is still in its infancy. Current detection methods for SLD, such as PCR and culturing, only detect an active infection and will not give any indication of a past infection from which the bacteria have been cleared. An immunological assay, on the other hand, can provide information on previous infections and therefore is crucial in vaccine development against SLD. In the present study, we have developed the first immunoassay capable of detecting C. hepaticus-specific antibodies present in the sera of infected birds. The assay uses C. hepaticus total protein extract (TPE) as the antigen coating on enzyme-linked immunosorbent assay (ELISA) plates. The cross reactivity of C. hepaticus antibodies with closely related C. jejuni and C. coli antigens was successfully overcome by pre-absorbing the sera using C. jejuni cell extracts. The assay was validated using sera samples from both naturally- and experimentally-infected birds, birds vaccinated with formalin-killed bacteria, and serum samples from SLD-negative birds (control group). The optimized ELISA assay had 95.5% specificity and 97.6% sensitivity. The immunoassay provides a useful tool for monitoring the exposure of poultry flocks to C. hepaticus infection and can be used to direct and support vaccine development. HIGHLIGHTS The first immunoassay developed for Spotty Liver Disease (SLD). A useful method for detecting C. hepaticus-specific antibodies in birds. Highly specific (95.5%) and sensitive (97.6%) assay. A key tool for use in epidemiological studies and vaccine development.

Campylobacter-derived ligands induce cytokine and chemokine expression in chicken macrophages and cecal tonsil mononuclear cells.

Campylobacter jejuni colonizes the chicken gut at a high density without causing disease. However, consumption of poultry products contaminated with this bacterium causes gastroenteritis in humans. Therefore, it is critically important to reduce the Campylobacter burden in poultry products to prevent transmission to humans. Evidence indicates that enhancing intestinal mucosal immune responses is of paramount importance for preventing or reducing Campylobacter colonization in chickens. In view of this, the present study was undertaken to evaluate host responses to different C. jejuni-derived ligands, including lipooligosaccharide (LOS), outer membrane proteins (OMPs), and genomic DNA, with the ultimate goal of identifying a ligand with potent immunostimulatory capacity to serve as a mucosal vaccine adjuvant against enteric infections in chickens. The results revealed that C. jejuni pathogen-associated molecular patterns (PAMPs) varied in their ability to induce the expression of cytokines and chemokines in chicken macrophages and cecal tonsil mononuclear cells and nitric oxide production in macrophages. In addition, C. jejuni OMPs demonstrated superior activity over LOS and DNA ligands in eliciting cytokine expression associated with T helper (Th)1 and Th2 responses (interferon [IFN]-γ and interleukin [IL]-13, respectively), in addition to expression of pro-inflammatory cytokines (IL-1ß), chemokine (CXCLi2), and regulatory cytokines (IL-10 and TGFß1/4) in cecal tonsil cells. Importantly, in addition to their ability to induce innate responses, OMPs could also function as antigens to elicit C. jejuni-specific antibody responses and thereby confer dual protection against C. jejuni infection. Further studies are required to assess the protective efficacy of C. jejuni OMPs against C. jejuni infection in chickens.

Campylobacter bacteriophage DA10: an excised temperate bacteriophage targeted by CRISPR-cas.

BACKGROUND: Lytic bacteriophages that infect Campylobacter spp. have been utilized to develop therapeutic/decontamination techniques. However, the association of Campylobacter spp. and bacteriophages has been the focus of several strands of research aimed at understanding the complex relationships that have developed between predators and prey over evolutionary time. The activities of endogenous temperate bacteriophages have been used to evaluate genomic rearrangements and differential protein expression in host cells, and mechanisms of resistance to bacteriophage infection in campylobacters such as phase variation and CRISPR-mediated immunity. RESULTS: Temperate bacteriophage DA10 represents a novel excised and infective virus capable of replication in a restricted set of C. jejuni and C. coli hosts. Whole genome sequencing reveals that DA10 (35,379 bp) forms part of a novel group of temperate bacteriophages that have limited distribution among database host genome sequences. Analysis of potential host genomes reveals a robust response against DA10 and DA10-like bacteriophages is driven by CRISPR-mediated immunity with 75% of DA10 ORFs represented as ~ 30 bp spacer sequences in numerous Campylobacter Type II-C CRISPR arrays. Several DA10-like homologues have been identified in a small sub-set of C. jejuni and C. coli genome sequences (ranging from near complete integrated prophage sequences to fragments recognisable in the sequence read archive). CONCLUSIONS: A complete intact DA10-like prophage in C. jejuni CJ677CC520 provides evidence that the associations between host and DA10-like bacteriophages are long-standing in evolutionary timescales. Extensive nucleotide substitution and loss can be observed in the integrated DA10-like prophage of CJ677CC520 compared to other relatives as observed through pairwise genome comparisons. Examining factors that have limited the population expansion of the prophage, while others appear to have thrived and prospered (Mu-like, CJIE-like, and lytic Campylobacter bacteriophages) will assist in identifying the underlying evolutionary processes in the natural environment.

Occupational risk of salmonellosis and campylobacteriosis: a nationwide population-based registry study.

OBJECTIVES: Occupational exposure to animals and foods thereof is a poorly characterised risk factor for salmonellosis and campylobacteriosis, the main causes of bacterial gastroenteritis in the Western world. We performed a population-based registry study in the Netherlands to assess whether differences exist in the incidence of reported salmonellosis and campylobacteriosis cases among occupational groups, and whether they can be explained by differences in the magnitude of exposure to these pathogens, as defined by serology. METHODS: Person-level occupational data for all Dutch residents were linked to lab-confirmed salmonellosis and campylobacteriosis data, and to serological data from a previous national serosurvey. SIRs for salmonellosis and campylobacteriosis among occupational sectors and specific high-risk occupations were calculated based on the total employed population. Moreover, Salmonella and Campylobacter seroincidence rates were compared among sectors and high-risk occupations. RESULTS: Occupational exposure to live animals or manure and working in the sale of animal-derived food products were associated with significantly increased risks of salmonellosis (SIR 1.55-1.82) and campylobacteriosis (SIR 1.36-1.65). Moreover, incidences were significantly higher in specific industrial sectors, as well as healthcare and social work sectors. Mean seroincidence rates ranged from 1.28 to 2.30 infections/person-year for Campylobacter, and from 0.36 to 0.99 for Salmonella, with only slightly higher rates for people in high-risk occupations. CONCLUSIONS: Significant differences in reported salmonellosis and campylobacteriosis incidence exist among occupational sectors, with the highest incidence in those persons occupationally exposed to live animals. These differences are only partially reflected in the serology.

In planta expression of nanobody-based designer chicken antibodies targeting Campylobacter.

Campylobacteriosis is a widespread infectious disease, leading to a major health and economic burden. Chickens are considered as the most common infection source for humans. Campylobacter mainly multiplies in the mucus layer of their caeca. No effective control measures are currently available, but passive immunisation of chickens with pathogen-specific maternal IgY antibodies, present in egg yolk of immunised chickens, reduces Campylobacter colonisation. To explore this strategy further, anti-Campylobacter nanobodies, directed against the flagella and major outer membrane proteins, were fused to the constant domains of chicken IgA and IgY, combining the benefits of nanobodies and the effector functions of the Fc-domains. The designer chimeric antibodies were effectively produced in leaves of Nicotiana benthamiana and seeds of Arabidopsis thaliana. Stable expression of the chimeric antibodies in seeds resulted in production levels between 1% and 8% of the total soluble protein. These in planta produced antibodies do not only bind to their purified antigens but also to Campylobacter bacterial cells. In addition, the anti-flagellin chimeric antibodies are reducing the motility of Campylobacter bacteria. These antibody-containing Arabidopsis seeds can be tested for oral passive immunisation of chickens and, if effective, the chimeric antibodies can be produced in crop seeds.

Immune response-eliciting exposure to Campylobacter vastly exceeds the incidence of clinically overt campylobacteriosis but is associated with similar risk factors: A nationwide serosurvey in the Netherlands.

BACKGROUND: We aimed to estimate population-level exposure to Campylobacter and associated risk factors, using three approaches for serological data analysis. METHODS: Nationwide, population-based serosurvey in the Netherlands (Feb 2006-Jun 2007). Anti-Campylobacter IgG, IgM and IgA were measured using ELISA, and analysed via: a) seroincidence estimation, using reference values of antibody peak levels and decay rates over-time after Campylobacter exposure; b) two normal distributions of true positives/negatives fitted to the IgG distribution to derive seroprevalence and individual probability of being positive/negative; and c) IgG levels. Risk factors were analysed using multiple linear regressions. RESULTS: From 1559 respondents, seroincidence was estimated at 1.61 infections/person-year (95%CI:1.58-1.64) and seroprevalence at 68.1% (65.4-70.9). The three approaches identified similar risk factors, although seroincidence had higher power and results were interpretable as risk: seroincidence was higher in females [exp(b) = 1.07(1.04-1.11)], older ages [vs. 15-34 years; for < 5, 5-14, 35-54 and 55-70 years: 0.60(0.58-0.63), 0.74(0.71-0.78), 1.08(1.03-1.13) and 1.08(1.01-1.16), respectively], non-Dutch background [Moroccan/Turkish: 1.25(1.14-1.37); Caribbean: 1.14(1.03-1.25)], low socioeconomic status [1.05(1.01-1.10)], traveling outside Europe [1.05(1.01-1.09)], and eating undercooked meat [1.04(1.01-1.08)]. CONCLUSION: Campylobacter exposure is much higher than clinical infection rates, but risk factors are similar to those previously described.Seroincidence is a powerful measure to study Campylobacter epidemiology, and is preferred over other methods.

Evaluation of the Diagnostic Accuracy of Two Immunochromatographic Tests Detecting Campylobacter in Stools and Their Role in Campylobacter Infection Diagnosis.

The detection of campylobacters in stools is performed essentially by culture, but this technique has a low sensitivity. New detection methods are now available. Among them, immunochromatography tests (ICTs) are very attractive in that they offer a result within 15 min. However, previous studies suggest that these tests have a relatively low specificity. The objective of this study was to evaluate the performance of these tests. During the study period, all patients who consulted the emergency units and had a stool culture were included. Their stool samples were tested with two ICTs, Ridaquick Campylobacter and ImmunoCard STAT! Campy. Stools were also tested by a home-made PCR and two commercially available enzyme-linked immunosorbent assays (ELISAs) when one of the ICTs was positive. The composite reference standard (CRS) was defined as positive if the culture was positive or, in case of a negative culture, if the PCR and one of the ELISAs were positive simultaneously. Three hundred and five patients were included. Among the 50 positive specimens with Ridaquick Campylobacter, 47 were considered true positives by the CRS, corresponding to a positive predictive value (PPV) of 94.0%. Among the 52 positive specimens with ImmunoCard STAT! Campy, 44 were considered true positives by the CRS, corresponding to a PPV of 84.6%. The negative predictive values were estimated at 94.9 and 92.4% for the Ridaquick Campylobacter and ImmunoCard STAT! Campy tests, respectively. ICTs appear to be very efficient and allow a very rapid detection of campylobacters, which is important for treating early campylobacter infections with an adapted antibiotherapy.

Evaluation of recombinant Salmonella vaccines to provide cross-serovar and cross-serogroup protection.

Historically, Salmonella vaccines have been either live attenuated or killed bacterin vaccines that fail to offer cross-serogroup protection, which limits risk mitigation and protection of consumers. Subunit recombinant vaccines which possess highly conserved antigens offer potential to provide cross-serogroup protection, and the ability to express immune-enhancing molecules that promote recognition by the immune system. Six Salmonella subunit vaccine candidates were developed in either attenuated S. Enteritidis (SE) or S. Typhimurium (ST) that cell-surface express antigenic epitopes of high mobility group box 1 immune-enhancing sequence (H), peptidoglycan associated lipoprotein (P), and Omp18 protein Cj0113 (C) in different pattern arrangements for evaluation against S. Heidelberg (SH) challenge in broilers. In exp. 1, chicks were orally vaccinated with SE-CPH, SE-HCP, SE-CHP, ST-CPH, ST-HCP, or ST-CHP at 1 × 107 cfu/chick, or saline on d 1 and d 14. On d 17 all birds were challenged with 6 × 106 cfu/chick SH, and ceca collected on d 23 and d 28. On d 23 only SE-CPH reduced (P < 0.05) SH recovery at 0.34 ± 0.23 log10 cfu when compared to control at 1.19 ± 0.26 log10 cfu. On d 28, SE-CPH and ST-HCP reduced SH recovery at 0.40 ± 0.40 and 0.51 ± 0.26 log10 cfu, respectively in comparison to control at 1.36 ± 0.23 log10 cfu. For exp. 2, chicks were orally vaccinated with 1 × 108 cfu/chick SE-CPH, SE-HCP, SE-CHP or saline on d 1. At d 7 all chicks were orally challenged with 7 × 106 cfu/chick SH and ceca collected on d 28 and d 35. SE-CPH reduced (P < 0.05) SH recovery on d 28 when compared to control (6.16 ± 0.13 vs. 4.71 ± 0.55 log10 cfu). In exp 3, chicks were vaccinated by spray in a commercial vaccination cabinet with SE-CPH vaccination, 1.6 × 107 cfu/chick, or saline. Birds were challenged on d 14 with 3 × 107 cfu/chick SH and ceca collected on d 18 and d 25. SE-CPH reduced SH recovery (P < 0.05) on d 18, 2.75 ± 0.05 log10 cfu, and d 25, 1.89 ± 0.43 log10 cfu, as compared to control chickens at 5.6 ± 0.37 (d 18) and 3.98 ± 0.5 log10 cfu (d 25). The results of these experiments suggest that cross-serogroup protection is possible using these SE and ST-vectored subunit vaccines.

Promising new vaccine candidates against Campylobacter in broilers.

Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1) significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

[Evaluation of a Newly Developed Campylobacter Antigen Detection Kit for Patients with Enteritis].

The newly developed rapid diagnostic test (RDT, DK14-CA1, Denka Seiken Co., Ltd.) to detect Campylobacter antigen was evaluated using fecal specimens of patients with enteritis. The RDT is an immunochromatographic assay using colored latex and can detect Campylobacter antigen (C. jejuni and C. coli) from patients' stool samples within 15 minutes. A total of 227 stool samples obtained from patients with enteritis were examined and the results were compared with conventional culture methods. Overall sensitivity, specificity, accuracy and positive predictive value (PPV) were 75.6%, 98.6%, 89.9% and 97.0% respectively. Among 53 severe cases defined with their clinical findings, sensitivity, specificity, accuracy and PPV were 82.1%, 100%, 90.6% and 100% respectively. Mean time to obtain the result with the RDT was 7 minutes whereas the culture method took 2.2 days. This study revealed the usefulness of the newly developed RDT as a rapid detection tool for Campylobacter antigen. Although the RDT has a little lower sensitivity compared with culture method, the simple and rapid test can contribute to treatment decisions for patients with enteritis and can be used at the patient's bedside and in outpatient clinics.

Immunologic characteristics of human gingival fibroblasts in response to oral bacteria.

BACKGROUND AND OBJECTIVE: There is ample evidence that gingival fibroblasts (GFs) participate in the immune response to oral bacteria and serve as immune-regulatory cells. The objective of this study was to investigate the innate immune response of GFs to oral bacteria. MATERIAL AND METHODS: Human GFs were cocultured with relatively less-pathogenic (Leptotrichia wadei, Fusobacterium nucleatum and Campylobacter gracilis) and pathogenic red-complex bacteria. The expression of mRNA for antimicrobial peptides [AMPs; namely human beta defensins (HBDs)], chemokines with antimicrobial activity [chemokine C-X-C motif (CXCL)10, CXCL11 and chemokine C-C motif ligand 20 (CCL20)] and proinflammatory mediators [interleukin (IL)6 and IL8] and the levels of CXCL11, CCL20, IL-6 and IL-8 accumulated in supernatants were analyzed using real-time PCR and ELISA, respectively. The proteolytic activities of CXCL11, CCL20, IL-6 and IL-8 produced by six species of bacteria were also determined. RESULTS: The relatively less-pathogenic bacteria strongly up-regulated the expression of antimicrobial chemokines and proinflammatory mediators, whereas the red-complex bacteria stimulated low levels, or often suppressed, expression of these factors. Regarding the regulation of AMPs, the inhibition of HBD3, HBD106 and HBD107 mRNAs by Porphyromonas gingivalis was noticeable; however, differences between the two bacterial groups were not conspicuous. Differential degradation of proteins by the six bacterial species was observed: P. gingivalis and Treponema denticola degraded proteins well, whereas the other species degraded proteins to a relatively lower degree. CONCLUSION: The invasion of red-complex bacteria into gingival connective tissue can suppress the immune response of GFs and can be a source of persistent infection in connective tissue.

Development of a monoclonal antibody-based colony blot immunoassay for detection of thermotolerant Campylobacter species.

Campylobacter species, particularly thermotolerant Campylobacter spp., such as C. jejuni, are major human foodborne pathogens. Culture methods have been routinely used for the detection of this organism in various types of samples. An alternative, simple and rapid confirmation test(s) without further tedious biochemical tests would be useful. Meanwhile, Campylobacter-like colonies can be difficult to identify on agar plates overgrown with competitive bacteria, which can lead to false-negative results. This study was to develop a simple colony blot immunoassay using a new monoclonal antibody (Mab) produced in the present study for rapid screening, confirmation and quantification of campylobacters on culture agar plates. The procedure developed in this study was able to specifically detect thermotolerant Campylobacter spp., but not other non-thermotolerant Campylobacter and non-Campylobacter reference strains tested. This assay could detect 105 cells in a single dot. This assay showed 100% correlation with the culture method for the blotted membranes from 21 either chicken meat or vegetable samples experimentally inoculated with thermotolerant campylobacters. Among 101 natural samples of chicken meat (n=44), chicken feces (n=20) and vegetables (n=37), this assay also showed positive for 23 chicken meat and 14 fecal samples that were positive for thermotolerant campylobacters by culture method, and identified four additional suspects that were culture negative. Membranes stored at 4°C for at least 4years could also be used for this assay. The assay developed in this study can be used in quantitative study for immediate or archival usage, and for diagnostic test to preliminarily confirm the presence of thermotolerant Campylobacter on agar plates.

Oxidative and nitrosative stress defences of Helicobacter and Campylobacter species that counteract mammalian immunity.

Helicobacter and Campylobacter species are Gram-negative microaerophilic host-associated heterotrophic bacteria that invade the digestive tract of humans and animals. Campylobacter jejuni is the major worldwide cause of foodborne gastroenteritis in humans, while Helicobacter pylori is ubiquitous in over half of the world's population causing gastric and duodenal ulcers. The colonisation of the gastrointestinal system by Helicobacter and Campylobacter relies on numerous cellular defences to sense the host environment and respond to adverse conditions, including those imposed by the host immunity. An important antimicrobial tool of the mammalian innate immune system is the generation of harmful oxidative and nitrosative stresses to which pathogens are exposed during phagocytosis. This review summarises the regulators, detoxifying enzymes and subversion mechanisms of Helicobacter and Campylobacter that ultimately promote the successful infection of humans.

Immunoglobulin G response in patients with Campylobacter concisus diarrhea.

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.

Was the increase in culture-confirmed Campylobacter infections in Denmark during the 1990s a surveillance artefact?

In 1991, 1999 and 2006, randomly selected individuals from the Danish Central Personal Register provided a serum sample. From individuals aged 30 years and above, 500 samples from each year were analysed for Campylobacter IgG, IgA and IgM antibodies using a direct ELISA method. We applied a seroincidence calculator available from the European Centre for Disease Prevention and Control to perform a mathematical back-calculation to estimate the annual Campylobacter seroincidence in the Danish population. The estimated Campylobacter seroincidence did not differ significantly between the 1991, 1999 and 2006 studies although the reported number of culture-confirmed cases of Campylobacter infection increased 2.5 fold from 1993 to 1999 among individuals aged 30 years and above. This suggests that Campylobacter was widely present in the Danish population before the increase in poultry-associated clinical Campylobacter infections observed from 1993 to 2001 among individuals of this age groups.

Immunological Biomarkers in Postinfectious Irritable Bowel Syndrome.

BACKGROUND: There is a recognized need for biological markers to facilitate diagnoses of irritable bowel syndrome (IBS) and to distinguish it from other functional and organic disorders. As postinfectious IBS (PI-IBS) is believed to account for as many as one third of all IBS cases, here we sought to identify differences in specific cytokines and serologic responses across patients with idiopathic IBS and PI-IBS and healthy controls. METHODS: At total of 120 US military personnel were identified from the Defense Medical Surveillance System-based International Classification of Diseases, 9th Revision, Clinical Modification (ICD9-CM) codes recorded during medical encounters and were grouped based on infectious gastroenteritis (IGE) episode (Shigella, Campylobacter, Salmonella, or an unspecified pathogen) followed by IBS, IBS without antecedent IGE, or IGE without subsequent IBS within 2 years of the IGE exposure. Sera from subjects were assayed for cytokine levels and antibodies against a panel of microbiome antigens. RESULTS: In total, 10 of 118 markers considered were shown to differ between IBS patients and healthy controls, including cytokines interleukin-6 (IL-6), IL-8, IL-1ß, and macrophage inflammatory protein-1ß (MIP-1ß), as well as antibody responses to microbial antigens. Antimicrobial antibody response profiles also differed between PI-IBS cases compared with IBS cases without an antecedent episode of acute IGE. Comparisons also suggest that immunoglobulin A (IgA) and IgG profiles may point to pathogen-specific origins among PI-IBS cases. CONCLUSION: Taken together, these results provide further evidence as to the molecular distinctness of classes of IBS cases and that serum biomarkers may prove useful in elucidating their pathobiological pathways.