Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice.

Introduction: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored. Methods: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques. Results: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni. Discussion: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.

Protective effect of Lactiplantibacillus plantarum LP5 in a murine model of colonisation by Campylobacter coli DSPV458.

Thermotolerant Campylobacter species are the leading cause of foodborne bacterial diarrheal disease worldwide. Campylobacter coli, abundant in pigs and pork products, have been identified as a source of human infection. In this study, we propose the use of Lactiplantibacillus plantarum LP5 as a probiotic to reduce colonisation of this intestinal pathogen in a murine colonisation model of C. coli DSPV458. Six-week-old adult female Balb/cCmedc mice were housed in groups: Control, Campy and Pro-Campy. Control and Pro-Campy groups received antibiotics for 5 days and the Campy group for 12 days. Pro-Campy group was inoculated for 7 days with 8.78 log10 cfu total of L. plantarum LP5 suspended in De Man, Rogosa and Sharpe broth. All groups were inoculated with 6.72 log10 cfu of C. coli DSPV458 suspended in brain heart infusion broth. L. plantarum LP5 was recovered only in the Pro- Campy group. C. coli DSPV458 was recovered at higher levels in the Control and Campy groups. The differences with the Pro-Campy group were significant. As regards faeces, Control and Campy groups reached 7.41 and 7.84 log10 cfu/g, respectively, and the Pro-Campy group only 4.62 log10 cfu/g. In the caecum, Control and Campy groups reached 8.01 and 9.26 log10cfu/g, respectively, and the Pro-Campy group only 4.51 log10 cfu/g. In the ileum, Control and Campy groups reached 3.43 and 3.26 log10 cfu/g, respectively, and the Pro-Campy group did not show detectable levels. The reduction of C. coli DSPV458 in the Pro-Campy group compared to the Control group in faeces, caecum and ileum was 99.55, 99.98 and 100%, respectively. Animals were maintained under normal health conditions, and haematological parameters were within the standard values for Balb/cCmedc. The incorporation of a probiotic generated a protective effect in the mice colonisation model. The protective effect would also apply to intestinal colonisation by indigenous enterobacteria. Therefore, the strategy used in this study is of great importance to understand the protection mechanisms in a murine model, as well as its application in food-producing animals.

Bacteriophage Therapy to Reduce Colonization of Campylobacter jejuni in Broiler Chickens before Slaughter.

Campylobacteriosis is the most commonly reported gastrointestinal disease in humans. Campybacter jejuni is the main cause of the infection, and bacterial colonization in broiler chickens is widespread and difficult to prevent, leading to high risk of occurrence in broiler meat. Phage therapy represents an alternative strategy to control Campylobacter in poultry. The aim of this work was to assess the efficacy of two field-isolated bacteriophages against experimental infections with an anti-microbial resistant (AMR) Campylobacter jejuni strain. A two-step phage application was tested according to a specific combination between chickens' rearing time and specific multiplicities of infections (MOIs), in order to reduce the Campylobacter load in the animals at slaughtering and to limit the development of phage-resistant mutants. In particular, 75 broilers were divided into three groups (A, B and C), and phages were administered to animals of groups B and C at day 38 (Φ 16-izsam) and 39 (Φ 7-izsam) at MOI 0.1 (group B) and 1 (group C). All broilers were euthanized at day 40, and Campylobacter jejuni was enumerated in cecal contents. Reductions in Campylobacter counts were statistically significant in both group B (1 log10 colony forming units (cfu)/gram (gr)) and group C (2 log10 cfu/gr), compared to the control group. Our findings provide evidence about the ability of phage therapy to reduce the Campylobacter load in poultry before slaughtering, also associated with anti-microbial resistance pattern.

Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice.

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10-/- mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.

How does feedback from phage infections influence the evolution of phase variation in Campylobacter?

Campylobacter jejuni (C. jejuni) causes gastroenteritis following the consumption of contaminated poultry meat, resulting in a large health and economic burden worldwide. Phage therapy is a promising technique for eradicating C. jejuni from poultry flocks and chicken carcasses. However, C. jejuni can resist infections by some phages through stochastic, phase-variable ON/OFF switching of the phage receptors mediated by simple sequence repeats (SSR). While selection strength and exposure time influence the evolution of SSR-mediated phase variation (PV), phages offer a more complex evolutionary environment as phage replication depends on having a permissive host organism. Here, we build and explore several continuous culture bacteria-phage computational models, each analysing different phase-variable scenarios calibrated to the experimental SSR rates of C. jejuni loci and replication parameters for the F336 phage. We simulate the evolution of PV rates via the adaptive dynamics framework for varying levels of selective pressures that act on the phage-resistant state. Our results indicate that growth reducing counter-selection on a single PV locus results in the stable maintenance of the phage, while compensatory selection between bacterial states affects the evolutionary stable mutation rates (i.e. very high and very low mutation rates are evolutionarily disadvantageous), whereas, in the absence of either selective pressure the evolution of PV rates results in mutation rates below the basal values. Contrastingly, a biologically-relevant model with two phase-variable loci resulted in phage extinction and locking of the bacteria into a phage-resistant state suggesting that another counter-selective pressure is required, instance, the use of a distinct phage whose receptor is an F336-phage-resistant state. We conclude that a delicate balance between counter-selection and phage-attack can result in both the evolution of phase-variable phage receptors and persistence of PV-receptor-specific phage.

Campylobacter coli bacteraemia: how common is it?

Campylobacter species are known to cause enteritis. However, over the past 40-50 years, there have been reports of varying presentations, such as cellulitis, spondylodiscitis and bacteraemia. Of the Campylobacter species, Campylobacter jejuni is the most common culprit for causing bacteraemia, however, Campylobacter coli bacteraemia is becoming more prevalent. Here, we discuss an unusual case of C. coli bacteraemia in a patient with decompensated liver cirrhosis.

Campylobacter upsaliensis isolated from a giant hepatic cyst.

Campylobacter upsaliensis is an enteropathogenic bacterium in animals, and is also rarely isolated from humans, where it can cause enteritis and bacteremia. This report describes the first case of isolation of C. upsaliensis from an infected giant hepatic cyst. This bacterium could not be cultured from abscess punctuate in a usual Campylobacter-selection medium (charcoal cefoperazone deoxycholate agar medium), because of high concentration of cefoperazone as a selection agent. It could not identified by matrix-assisted laser desorption ionization-time of flight mass spectrum. Rather, it was identified as C. upsaliensis by whole genome sequencing, including by multilocus sequence typing.

Clinical features of campylobacter-associated benign convulsions with mild gastroenteritis compared with rotavirus convulsions.

PURPOSE: The aim of the present study was to compare the clinical features of campylobacter-associated benign convulsions with mild gastroenteritis (BCWG) with rotavirus-associated BCWG in China. METHODS: The medical records of BCWG patients admitted to Children's Hospital of Jiangxi Province in China between January 2015 and January 2017 were reviewed in this retrospective study. RESULTS: Ultimately, 318 patients were diagnosed with BCWG. Two hundred and two cases were tested for Campylobacter jejuni antigen, and seven (3.47%) were positive. A total of 248 cases were tested for rotavirus antigen, and 44 (17.74%) were positive. Campylobacter-associated BCWG occurred in summer and autumn. In contrast, rotavirus-associated BCWG mainly occurred in winter. In the campylobacter-associated BCWG group, five patients (71.43%) had two or more seizures. In one patient(14.29%), the seizure occurred on the first day of gastroenteritis; three patients (42.86%) had seizures on the second day, and three (42.86%) had seizures on the third day or later. Thirteen seizures were observed in the campylobacter-associated BCWG group; of these, 11 (84.62%) lasted less than 5 min, and 11 (84.62%) were generalized seizures. Phenobarbital (5 mg/kg/time) was effective in all 6 cases (100%) in which it was used. Other than the different seasonal distributions, the clinical features of campylobacter-associated BCWG and rotavirus-associated BCWG may be similar. CONCLUSIONS: Campylobacter is one of the pathogens responsible for BCWG, especially in summer and autumn. Other than the different seasonal distributions, the clinical features of campylobacter-associated BCWG and rotavirus-associated BCWG may be similar.

Spotlight on avian pathology: Campylobacter hepaticus, the cause of Spotty Liver Disease in layers.

Campylobacter hepaticus was recently identified as the aetiological agent of Spotty Liver Disease (SLD). SLD causes significant health and productivity losses in the Australian egg industry and the disease is present in other countries. Following the isolation and characterization of C. hepaticus, molecular tools and refined culturing methods have been developed to identify the pathogen. It is suspected that the application of these tools will lead to identification of the pathogen in many poultry production systems throughout the world. As C. hepaticus has only recently been identified, little is known about the mechanisms of pathogenesis and, hence, new research needs to be directed towards understanding SLD epidemiology and C. hepaticus virulence mechanisms to inform efforts to develop intervention strategies.

Mycotic aortic aneurysms treated by endovascular repair: initial experience in a single center.

INTRODUCTION: Mycotic aortic aneurysm (MAA) is an uncommon cause of aneurysmal aortic disease. However, it may have an aggressive presentation and a complicated early outcome. Endovascular aneurysm repair (EVAR) of MAA is emerging as an alternative to open repair (OR) for the treatment of these aneurysms, particularly in high-risk surgical patients. We report a single-center experience with the endovascular management of mycotic aortic aneurysms. MATERIAL AND METHODS: Two mycotic abdominal aortic aneurysms were treated with an endovascular stent graft at Centre Hospitalier Régional du Val de Sambre, Belgium. The mean follow-up was 15 months. Technical success was achieved in all two patients. CT-scan follow up showed shrinkage of the aneurysm sac, with no evidence of infection along the stent graft and no signs of endoleakage in all patients. One patient died during the follow-up period from a cause unrelated to the aneurysm. CONCLUSION: EVAR is an effective and safe option and might be a suitable alternative to OR in the absence of predictors of poor prognosis for the treatment of non-complicated forms of MAA.

Pathway based therapeutic targets identification and development of an interactive database CampyNIBase of Campylobacter jejuni RM1221 through non-redundant protein dataset.

The bacterial species Campylobacter jejuni RM1221 (CjR) is the primary cause of campylobacteriosis which poses a global threat for human health. Over the years the efficacy of antibiotic treatment is becoming more fruitless due to the development of multiple drug resistant strains. Therefore, identification of new drug targets is a valuable tool for the development of new treatments for affected patients and can be obtained by targeting essential protein(s) of CjR. We conducted this in silico study in order to identify therapeutic targets by subtractive CjR proteome analysis. The most important proteins of the CjR proteome, which includes chokepoint enzymes, plasmid, virulence and antibiotic resistant proteins were annotated and subjected to subtractive analyses to filter out the CjR essential proteins from duplicate or human homologous proteins. Through the subtractive and characterization analysis we have identified 38 eligible therapeutic targets including 1 potential vaccine target. Also, 12 potential targets were found in interactive network, 5 targets to be dealt with FDA approved drugs and one pathway as potential pathway based drug target. In addition, a comprehensive database 'CampyNIBase' has also been developed. Besides the results of this study, the database is enriched with other information such as 3D models of the identified targets, experimental structures and Expressed Sequence Tag (EST) sequences. This study, including the database might be exploited for future research and the identification of effective therapeutics against campylobacteriosis. URL: (http://nib.portal.gov.bd/site/page/4516e965-8935-4129-8c3f-df95e754c562#Banner).

Lactobacillus johnsonii ameliorates intestinal, extra-intestinal and systemic pro-inflammatory immune responses following murine Campylobacter jejuni infection.

Campylobacter jejuni infections are progressively increasing worldwide. Probiotic treatment might open novel therapeutic or even prophylactic approaches to combat campylobacteriosis. In the present study secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally reassociated with a commensal murine Lactobacillus johnsonii strain either 14 days before (i.e. prophylactic regimen) or 7 days after (i.e. therapeutic regimen) peroral C. jejuni strain 81-176 infection. Following peroral reassociation both C. jejuni and L. johnsonii were able to stably colonize the murine intestinal tract. Neither therapeutic nor prophylactic L. johnsonii application, however, could decrease intestinal C. jejuni burdens. Notably, C. jejuni induced colonic apoptosis could be ameliorated by prophylactic L. johnsonii treatment, whereas co-administration of L. johnsonii impacted adaptive (i.e. T and B lymphocytes, regulatory T cells), but not innate (i.e. macrophages and monocytes) immune cell responses in the intestinal tract. Strikingly, C. jejuni induced intestinal, extra-intestinal and systemic secretion of pro-inflammatory mediators (such as IL-6, MCP-1, TNF and nitric oxide) could be alleviated by peroral L. johnsonii challenge. In conclusion, immunomodulatory probiotic species might offer valuable strategies for prophylaxis and/or treatment of C. jejuni induced intestinal, extra-intestinal as well as systemic pro-inflammatory immune responses in vivo.

Administration of Lactobacillus johnsonii FI9785 to chickens affects colonisation by Campylobacter jejuni and the intestinal microbiota.

1. Campylobacter jejuni is the most common bacterial cause of human food-borne gastroenteritis in the world. A major source of human infection is the consumption of contaminated meat, particularly poultry. New control measures to reduce or eliminate this pathogen from the animal gastrointestinal tract are urgently required, and the use of probiotics as competitive exclusion agents is a promising biocontrol measure to reduce C. jejuni in the food chain. 2. In this study, we assessed the potential of Lactobacillus johnsonii FI9785, which has shown efficacy against Clostridium perfringens, to combat C. jejuni. The effect of prophylactic administration of L. johnsonii on the ability of C. jejuni to colonise chickens was determined. 3. Two doses of L. johnsonii given a week apart led to a reduction in C. jejuni colonisation in the caecal contents, but this biocontrol seemed reliant upon a high level of initial colonisation by the probiotic. 4. The microbial composition in the chicken gut was significantly altered by the probiotic treatment, as shown by denaturing gradient gel electrophoresis of 16S rRNA gene amplicons. 5. Together these results demonstrate the potential of this probiotic strain to be tested further as a competitive exclusion agent in poultry against C. jejuni.

Fatal Campylobacter jejuni ileocolitis.

Campylobacter infection usually starts in the jejunum and ileum and progresses distally. The case fatality rate is low and most occur in elderly or patients with comorbidity as in this case. Antibiotics should be used in severe cases or patients at risk. The choices are macrolides and fluoroquinolones. However, in some countries quinolone resistance is increasing, as in Spain. We shouldn´t forget this fact for the proper treatment approach and specifically in refractory cases.

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment.

INTRODUCTION: Guillain-Barré syndrome is a rare disease representing the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month. The etiology and pathogenesis remain largely enigmatic and the syndrome results in death or severe disability in 9-17% of cases despite immunotherapy. Areas covered: In terms of etiology, Guillain-Barré syndrome is linked to Campylobacter infection but less than 0.1% of infections result in the syndrome. In terms of pathogenesis, activated macrophages and T cells and serum antibodies against gangliosides are observed but their significance is unclear. Expert commentary: Guillain-Barré syndrome is a heterogeneous condition with numerous subtypes and recent data point towards the role of ganglioside epitopes by immunohistochemical methods. Ultimately, the syndrome results from a permissive genetic background on which environmental factors, including infections, vaccination and the influence of aging, lead to disease.

Infección extraintestinal debida a bacterias del género Campylobacter / Extraintestinal infections due to Campylobacter SPP

Campylobacter jejuni causa principalmente enteritis disenteriforme; los casos debidos a C. fetus son raros, mayormente bacteriemiaen inmunosuprimidos. Presentamos dos casos de enfermedad diarreica con bacteriemia, ambos con hemorragia digestiva,debida a C. jejuni, un caso inusual de infección de anerurisma de la arteria femoral y un caso de bacteriemia recurrente conprobable foco en marcapasos en un anciano sin otro factor de inmunosupresión, los dos últimos debidos a C. fetus. Todos lospacientes tuvieron evolución favorable. Recomendamos prestar atención a los hemocultivos que resulten positivos para efectuarlos subcultivos adecuados para recuperar, identificar y determinar la sensibilidad a los antimicrobianos de este tipo de bacterias microaerofílicas.

Campylobacter jejuni often causes enteritis; cases due to C. fetus are rare: it causes mostly bacteremia in patients with immunosuppression.We present two cases of diarrheal disease with bacteremia, both with gastrointestinal bleeding due to C. jejuni, an unusual case ofC. fetus infection of an aneurysm in the femoral artery, and one case of recurrent C. fetus bacteremia with probably focus in apacemaker in an elderly patient without another cause of immunosuppression. All patients had a favorable evolution. We recommendspecial attention to the positive blood cultures in order to recover and identify this type of microaerophilic bacteria, and determineantimicrobial susceptibility.

Salmonella and Campylobacter: Antimicrobial resistance and bacteriophage control in poultry.

Salmonella and Campylobacter are major causes of foodborne related illness and are traditionally associated with consuming undercooked poultry and/or consuming products that have been cross contaminated with raw poultry. Many of the isolated Salmonella and Campylobacter that can cause disease have displayed antimicrobial resistance phenotypes. Although poultry producers have reduced on-the-farm overuse of antimicrobials, antimicrobial resistant Salmonella and Campylobacter strains still persist. One method of bio-control, that is producing promising results, is the use of lytic bacteriophages. This review will highlight the current emergence and persistence of antimicrobial resistant Salmonella and Campylobacter recovered from poultry as well as bacteriophage research interventions and limitations.

A review of sexually transmitted bovine trichomoniasis and campylobacteriosis affecting cattle reproductive health.

The objective is to discuss sexually transmitted diseases caused by Tritrichomonas foetus (T foetus) and Campylobacter fetus (C fetus) subsp. venerealis, with a focus on prevalence, pathogenesis, and diagnosis in cows and bulls. Diagnosis and control are problematic because these diseases cause severe reproductive losses in cows, but in bulls are clinically asymptomatic, which allows the disease to flourish, especially in the absence of legislated control programs. We review research regarding prophylactic systemic immunization of bulls and cows with antigens of T foetus and C fetus venerealis and their efficacy in preventing or clearing preexisting infections in the genital tract. Current diagnostic methods of C fetus venerealis and T foetus (microbial culture and PCR) should be improved. Review of the latest advances in bovine trichomoniasis and campylobacteriosis should promote knowledge and provide an impetus to pursue further efforts to control bovine sexually transmitted diseases.