Campylobacter Jejuni Infection Research Articles

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. We identified 166 patients with neurological symptoms appearing in less than 1month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1year follow-up. One patient died, and 15% of patients relapsed. Age > 70years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12months. No predictors of relapse were identified. This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Critical Care in Guillain–Barré Syndrome

AbstractGuillain–Barré syndrome (GBS) is an autoimmune polyneuropathy characterized by hyporeflexic neuromuscular paralysis and albuminocytologic dissociation in the cerebrospinal fluid. It is a postinfectious disorder. The most common antecedent illnesses are respiratory tract infection and Campylobacter jejuni infection. After the antecedent infection, specific antibodies are generated that cross-react with gangliosides in the host culminating in demyelination of the peripheral nerves or nerve roots. Complement activation also contributes to nerve degeneration. Bilateral symmetrical progression of the limb weakness occurs over a period of a few days followed by a plateau phase, after which a recovery phase follows. Generalized hypotonia and hyporeflexia characterize the limb weakness. Cerebrospinal fluid analysis shows albuminocytologic dissociation. About one-third of patients develop respiratory failure. Neuropathic pain is a disturbing symptom in GBS. Dysautonomia is very characteristic of GBS. Erasmus GBS respiratory insufficiency score predicts the need for mechanical ventilation. The weaning process from mechanical ventilation mainly depends on the recovery of vital capacity and inspiratory force. The definitive treatment for GBS consists of plasma exchange or intravenous immunoglobulin therapy both of which are equally efficacious. Seasonal variation has been observed in the occurrence and recovery of GBS. Prognosis of GBS varies widely. Erasmus GBS outcome scale scoring system predicts the ability of the patient to walk independently after 6 months. Several GBS cases have been reported globally during recent pandemic of coronavirus disease 2019. Though GBS is a self-limiting disease, there are quite a few research questions that still remain to be answered.

Anemic Gastrointestinal Bleeding in Campylobacter Jejuni Infection

We present a 13-month-old male with a history of multiple diarrheal episodes with mucus and blood due to Campylobacter Jejuni infection. He was admitted in the last of them due to mucosanguinous stools, fever and oral intolerance. He was treated with amoxicillin/clavulanic acid and a blood test was performed without leukocytosis (14 x109/L) but with neutrophilia (10.2 x109/L) and elevated CRP (85mg/L), in addition to abdominal ultrasound with minimal fluid tab in the right iliac fossa. On the second day of hospitalization, he presented an anemizing and painless gastrointestinal bleeding that required transfusion (hemoglobin 6.3g/dL), however, he was hemodynamically stable, with slightly painful abdomen in lower quadrants, but without peritoneal irritation.

Carvacrol prophylaxis improves clinical outcome and dampens apoptotic and pro-inflammatory immune responses upon Campylobacter jejuni infection of human microbiota-associated IL-10-/- mice.

Incidence rates of human Campylobacter jejuni infections are progressively increasing globally. Since the risk for the development of post-infectious autoimmune diseases correlates with the severity of the preceding enteritis and campylobacteriosis treatment usually involves symptomatic measures, it is desirable to apply antibiotic-independent compounds to treat or even prevent disease. Given its health-promoting including anti-inflammatory properties carvacrol constitutes a promising candidate. Thisprompted us to test the disease-alleviating including immune-modulatory effects of carvacrolprophylaxis in acute murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10-/- mice were orally challenged with synthetic carvacrol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas carvacrol prophylaxis did neither affect gastrointestinal pathogen loads, nor the human commensal gut microbiota composition, it improved the clinical outcome of mice, attenuated colonic epithelial cell apoptosis, and dampened pro-inflammatory immune responses not only in the intestinal tract but also in extra-intestinal organs including the liver and the spleen. In conclusion, our preclinical placebo-controlled intervention study provides convincing evidence that oral carvacrol pretreatment constitutes a promising option to mitigate acute campylobacteriosis and in turn, to reduce the risk for post-infectious complications.

Menthol Pretreatment Alleviates Campylobacter jejuni-Induced Enterocolitis in Human Gut Microbiota-Associated IL-10-/- Mice.

Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle- and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, non-toxic antibiotic-independent treatment approaches are highly desirable. Given its health-promoting properties, including anti-microbial and anti-inflammatory activities, we tested the disease-alleviating effects of oral menthol in murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10-/- mice were orally subjected to synthetic menthol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas menthol pretreatment did not improve campylobacteriosis symptoms, it resulted in reduced colonic C. jejuni numbers and alleviated both macroscopic and microscopic aspects of C. jejuni infection in pretreated mice vs. controls. Menthol pretreatment dampened the recruitment of macrophages, monocytes, and T lymphocytes to colonic sites of infection, which was accompanied by mitigated intestinal nitric oxide secretion. Furthermore, menthol pretreatment had only marginal effects on the human fecal gut microbiota composition during the C. jejuni infection. In conclusion, the results of this preclinical placebo-controlled intervention study provide evidence that menthol application constitutes a promising way to tackle acute campylobacteriosis, thereby reducing the risk for post-infectious complications.

The effect of Campylobacter jejuni challenge on the ileal microbiota and short-chain fatty acids at 28 and 35 days of age

Acetate is a short-chain fatty acid (SCFA) that plays an important role in maintaining intestinal barrier integrity. Campylobacter jejuni (C. jejuni) infection is hypothesised to decrease the presence of acetate-producing bacteria and, consequently, the overall acetate concentration in the ileum, leading to an impaired intestinal barrier. This study aimed to characterise the effect of the C. jejuni challenge on the ileal microbiota and SCFAs concentration in broilers. Sixty broiler chicks were randomly assigned to control and challenge treatments, each with six replications and five birds per replicate. At 21 days of age, birds were inoculated with PBS (control), or 1 × 108 CFU/bird C. jejuni in the challenge group. Body weight, feed intake and feed conversion ratio were measured weekly. Ileal mucus and contents were collected on days 28 and 35 for microbiome and SCFA analysis. C. jejuni challenge didn’t affect body weight, feed intake and feed conversion ratio at days 28 and 35 compared to the control group. C. jejuni didn’t affect alpha diversity compared to the control group. C. jejuni didn’t alter microbial function nor the relative abundances of the phyla, families, genera and species compared to the control group; however, C. jejuni decreased the ileal concentration of acetate on days 28 (p = .09) and 35 (p = .002) compared to the control group. In conclusion, the C. jejuni challenge didn’t alter microbial composition or function and except for the shifts in acetate concentration, it had minimal impact on birds’ intestinal environment, highlighting the near-commensal nature of C. jejuni in broilers.

Oral treatment of human gut microbiota associated IL-10-/- mice suffering from acute campylobacteriosis with carvacrol, deferoxamine, deoxycholic acid, and 2-fucosyl-lactose.

Food-borne Campylobacter jejuni infections constitute serious threats to human health worldwide. Since antibiotic treatment is usually not indicated in infected immune-competent patients, antibiotic-independent treatment approaches are needed to tackle campylobacteriosis. To address this, we orally applied carvacrol, deferoxamine, deoxycholate, and 2-fucosyl-lactose either alone or all in combination to human microbiota-associated IL-10-/- mice from day 2 until day 6 following oral C. jejuni infection. Neither treatment regimen affected C. jejuni loads in the colon, whereas carvacrol lowered the pathogen numbers in the ileum on day 6 post-infection (p.i.). The carvacrol and combination treatment regimens resulted in alleviated diarrheal symptoms, less distinct histopathological and apoptotic epithelial cell responses in the colon, as well as diminished numbers of colonic neutrophils and T lymphocytes on day 6 p.i., whereas the latter cells were also decreased upon deferoxamine, deoxycholate, or 2-fucosyl-lactose application. Remarkably, the carvacrol, deferoxamine, and combination treatment regimens dampened ex-vivo IFN-γ secretion in the colon, the kidneys, and even in the serum to basal concentrations on day 6 p.i. In conclusion, carvacrol alone and its combination with deferoxamine, deoxycholate, and 2-fucosyl-lactose constitute promising antibiotics-independent treatment options to fight acute campylobacteriosis.

Prophylactic Oral Application of Activated Charcoal Mitigates Acute Campylobacteriosis in Human Gut Microbiota-Associated IL-10-/- Mice.

The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10-/- mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis.

Reversible Conduction Failure in Guillain-Barré Syndrome

Gangliosides are the primary antigenic target in acute motor axonal neuropathy. When anti-ganglioside antibodies bind to gangliosides near the motor axon node of Ranvier, complement system activation and Wallerian degeneration occur. Nevertheless, debate persists regarding the impact of anti-ganglioside antibodies on Guillain-Barré syndrome (GBS). Certain patients with these antibodies experience a swift recovery or exhibit conduction abnormalities indicative of demyelination in nerve conduction studies. The concept of reversible conduction failure was introduced by Kuwabara et al. in 1998. They proposed that this could result from compromised physiological conduction at the node of Ranvier. Auto-antibodies that bind to GM1 or GD1a gangliosides at this node can activate the complement system and disrupt sodium channel and axo-glial junctions, causing conduction failure. In 2003, Cappaso et al. described two cases of rapidly improving flaccid paralysis following Campylobacter jejuni infection. Initial nerve conduction studies indicated motor conduction block, which resolved quickly within 2 to 5 weeks. The authors termed this phenomenon acute motor conduction block neuropathy and considered it a form of arrested or partial acute motor axonal neuropathy. Since acute motor conduction block neuropathy could be misclassified as acute inflammatory demyelinating polyneuropathy based on existing electrophysiological criteria, several suggestions were made to refine the classification of GBS subtypes.

Seroprevalence of Campylobacter jejuni infection in common subtypes of Guillain–Barre syndrome in Kashmiri population

BackgroundGuillain–Barre Syndrome (GBS) is a common differential diagnosis of acute-onset flaccid quadriparesis with or without bulbar involvement. Various illnesses precede GBS, respiratory illness being the most common. Campylobacter jejuni is the single most common organism found associated with GBS. The aim of the present study was to determine the prevalence of Campylobacter jejuni positivity in different subtypes of GBS.MethodsSixty patients of GBS were tested for serological evidence of Campylobacter jejuni and compared with 60 age and sex matched controls.ResultsMean age of cases was 39.58 (± 14.76 years) and that of controls was 35 (± 12.31 years). Preceding illness was present in 38% cases. Respiratory tract illness was present in 9 (15%) cases, while as GI illness was present in 8 (13%) cases. AIDP was the most common variant accounting for 65% of cases, followed by AMAN (18.3%). Among cases, 24 (40%) tested positive for Campylobacter jejuni antibody whereas only 12 (20%) tested positive for antibody among controls. The difference was statistically significant between cases and controls (p value = 0.003). There was no statistically significant difference in antibody positivity and preceding illness among different variants of GBS (p value = 1.0).ConclusionCampylobacter jejuni infection is a frequent preceding illness in GBS patients, although it may be asymptomatic. There is however no relation between different subtypes of GBS and C. jejuni infection.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

Not only for Christmas: Prophylactic oral application of trans-cinnamaldehyde alleviates acute murine campylobacteriosis.

The prevalence of Campylobacter jejuni infections is increasing worldwide and responsible for significant morbidities and socioeconomic expenses. The rise in antimicrobial resistance of C. jejuni underscoresthe urge for evaluating antibiotics-independent compounds as therapeutic and preventive treatment options of human campylobacteriosis. Given its well-known anti-microbial and immune-modulatory properties we here surveyed the disease-modifying effects of trans-cinnamaldehyde pretreatment in experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally challenged with trans-cinnamaldehyde starting 7 days prior C. jejuni infection. Whereas gastrointestinal colonization properties of the enteropathogens remained unaffected, trans-cinnamaldehyde pretreatment did not only improve clinical signs in infected mice, but also alleviated colonicepithelial cell apoptosis on day 6 post-infection. Furthermore, trans-cinnamaldehyde application resulted in less pronounced T cell responses in the colon that were accompanied bydampened proinflammatory mediator secretion in distinct intestinal compartments. Notably, theimmune-modulatory effects of trans-cinnamaldehyde were not restricted to the intestinal tract butcould also be observed in extra-intestinal organs such as the liver and kidneys. In conclusion, ourpreclinical placebo-controlled intervention study provides first evidence that due to its immune-modulatory effects, trans-cinnamaldehyde constitutes a promising prophylactic option to alleviate campylobacteriosis.

Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: a UK national case-series and review of the literature.

Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: a UK national case-series and review of the literature.

Recurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinants.

We present two independent cases of recurrent multidrug-resistant Campylobacter jejuni infection in immunocompromised hosts and the clinical challenges encountered due to the development of high-level carbapenem resistance. The mechanisms associated with this unusual resistance for Campylobacters were characterized. Initial macrolide and carbapenem-susceptible strains acquired resistance to erythromycin (MIC > 256mg/L), ertapenem (MIC > 32mg/L), and meropenem (MIC > 32mg/L) during treatment. Carbapenem-resistant isolates developed an in-frame insertion resulting in an extra Asp residue in the major outer membrane protein PorA, within the extracellular loop L3 that connects β-strands 5 and 6 and forms a constriction zone involved in Ca2+ binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167A|Gly56Asp) at PorA's extracellular loop L1. IMPORTANCE Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within porA. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.

Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports.

Immune checkpoint inhibitors (ICIs) have improved the prognosis in multiple cancer types. However, ICIs can induce immune-related adverse events such as immune-mediated enterocolitis (IMC). The gut microbiota may be implicated in IMC development. Therefore, we investigated fecal microbiota transplantation (FMT) as a treatment option for 2 patients with metastatic cancer suffering from refractory IMC. The patients were treated with, respectively, 1 and 3 FMTs after vancomycin pre-treatment. We monitored defecation frequency, fecal calprotectin, and microbiota composition. After FMT, both patients improved in defecation frequency, were discharged from the hospital, and received lower dosage of immunosuppressive therapy. Patient 1 developed an invasive pulmonary aspergillosis deemed to be related to prolonged steroid exposure. Patient 2 suffered from a Campylobacter jejuni infection after the first FMT and was treated with meropenem, resulting in a low-diversity microbiota profile and increased calprotectin levels and defecation frequency. After a second and third FMT, bacterial diversity increased and defecation frequency and calprotectin levels decreased. Pre-FMT, both patients showed low bacterial richness, but varying bacterial diversity. After FMT, diversity and richness were similar to healthy donor levels. In conclusion, FMT resulted in improvement of IMC symptoms and corresponding microbial changes in 2 cancer patients with refractory IMC. While more research is warranted, microbiome-modulation could be a promising new therapeutic option for IMC.

P-091 Primary intestinal lymphoma associated with enteric fistula to an intraperitoneal mesh: what came first?

Abstract Aim To present the possible association between the use of intraperitoneal mesh and the appearance of primary intestinal lymphoma. Material and Methods We present the case of a 67-year-old woman with a history of multiple abdominal surgeries (appendectomy, Hartmann's procedure for perforated diverticulitis and reoperation due to hemoperitoneum). Ventral hernia repair was performed placing intraperitoneal composite mesh in 2013. Eight years later, the patient consulted with abdominal pain and bulging located on previous laparotomy scar. Abdominal CT was carried out, demonstrating an intestinal fistula from the jejunum to the mesh with an adjacent 5 cm intraabdominal abscess. Results Elective surgery was decided on. An enteric fistula from the jejunum to the previous mesh was observed, as well as pathologic lymph nodes adhered to the mesh. Intestinal resection was performed prior mesh excision. Histopathological analysis was compatible with extranodal B-cell lymphoma of the marginal zone. Conclusions Enteric fistula rate associated with the use of intraperitoneal mesh is 0.3–4%. There are no published cases of intestinal lymphoma correlated with the use of intraperitoneal mesh. Primary intestinal lymphoma constitutes 1–4% of bowel malignancies. The most common type is extranodal marginal zone MALT B lymphoma. Typical locations are: gastric (50%), small bowel (33–40%) and colon (10–15%). Situations of chronic inflammation such as celiac disease, inflammatory bowel disease, Campylobacter jejuni infection or inflammatory reactions are known to cause this entity. In this particular case, an excessive inflammatory response to an intraperitoneal mesh resulting in enteric fistula could be the source of malignancy, or vice versa.

Immunopathogenesis of Campylobacter jejuniinfection in a small animal model

Abstract We set out to develop and characterize a small animal model of Campylobacter jejuni(CJ) infection that recapitulates human campylobacteriosis. Adult C57BL/6J mice are rendered susceptible to colonization and disease by pre-treatment with a zinc deficient diet and a broad-spectrum antibiotic cocktail. We have established this model with four strains with diverse capsular serotypes and flagellar groups, two key virulence factors for CJ pathogenesis. We measured colonization, weight loss, diarrhea, fecal inflammatory markers, and cytokine production by mesenteric lymphocytes and splenocytes. Diarrhea containing visible mucous and/or blood and degree of weight loss vary in severity depending on the strain and dose. Interestingly, we identified an inverse relationship between inoculum dose and levels of fecal inflammatory markers, with lower inoculum doses inducing significantly higher inflammation. We also observed production of IFNγ and IL-17 at day 9 post infection and despite no decrease in CJ colonization, IFNγ and IL-17 levels decreased by day 21 with a subsequent increase in IL-10 production. We also observed higher levels of IFNγ and IL-17 in mice challenged with strain CG8486 relative to those challenged with strain 81–176 pointing to potential strain differences. These differences observed were more striking in mesenteric lymphocytes versus splenocytes, indicating that local cellular responses differed from systemic responses. We have developed a model of inflammatory diarrhea in adult mice that exhibits hallmarks of CJ infection and further identified significant shifts in cytokine expression associated with the duration of infection, bacterial strain utilized, and therapeutic treatment. Research reported in this presentation is supported by Navy work unit number: 6000.RAD1.DA3.A0308 and CARB-X. CARB-X’s funding for this project is sponsored by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from Wellcome Trust, the UK Global Antimicrobial Resistance Innovation Fund (GAMRIF) funded by the UK Government Department of Health and Social Care (DHSC) and the Bill & Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. Disclaimers: The views expressed in this work are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. F. Poly is an employee of the U.S. Government. This work was prepared as part of official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties.The animal study protocol was reviewed and approved by the Naval Medical Research Center IACUC in compliance with all applicable Federal regulations governing the protection of animals in research.

Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis.

Given the worldwide increasing prevalence of human Campylobacter jejuni infections and the emergence of multi-drug resistant enteropathogenic strains, antibiotic-independent approaches applying non-toxic natural compounds for the treatment and prophylaxis of campylobacteriosis appear utmost desirable. In our placebo-controlled intervention study, we surveyed potential disease-alleviating including anti-pathogenic and immune-modulatory effects upon prophylactic oral application of lemon-essential oil (LEM-EO) and coriander-essential oil (COR-EO) in acute experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally challenged with either LEM-EO or COR-EO starting seven days prior to peroral C. jejuni infection. Six days post-infection, slightly lower pathogen loads were assessed in the colon of mice from the LEM-EO as opposed to the COR-EO cohort if compared to placebo counterparts. Prophylactic application of both EOs improved the clinical outcome of acute campylobacteriosis which was paralleled by less distinct pathogen-induced colonic epithelial cell apoptosis. Moreover, mice subjected to LEM-EO and COR-EO prophylaxis displayed lower colonic numbers of macrophages/monocytes and of T lymphocytes, respectively, whereas in both verum groups, basal IL-6 and IFN-γ concentrations were measured in mesenteric lymph nodes on day 6 post-infection. The oral challenge with either EOs resulted in diminished secretion of distinct pro-inflammatory mediators in the kidney as well as serum samples derived from the infected mice. In conclusion, the results from our preclinical in vivo study provide evidence that LEM-EO and COR-EO constitute promising prophylactic measures to prevent severe campylobacteriosis which may help to reduce the risk for development of post-infectious sequelae in C. jejuni infected individuals.

Therapeutic Oral Application of Carvacrol Alleviates Acute Campylobacteriosis in Mice Harboring a Human Gut Microbiota.

Human Campylobacter jejuni infections are rising globally. Since antibiotics are usually not indicated in acute campylobacteriosis, antibiotic-independent intervention measures are desirable. The phenolic compound carvacrol constitutes a promising candidate molecule given its antimicrobial and immune-modulatory features. To test the disease-alleviating effects of oral carvacrol treatment in acute murine campylobacteriosis, IL-10-/- mice harboring a human gut microbiota were perorally infected with C. jejuni and treated with carvacrol via the drinking water. Whereas C. jejuni stably established in the gastrointestinal tract of mice from the placebo cohort, carvacrol treatment resulted in lower pathogen loads in the small intestines on day 6 post infection. When compared to placebo, carvacrol ameliorated pathogen-induced symptoms including bloody diarrhea that was accompanied by less distinct histopathological and apoptotic cell responses in the colon. Furthermore, innate and adaptive immune cell numbers were lower in the colon of carvacrol- versus placebo-treated mice. Notably, carvacrol application dampened C. jejuni-induced secretion of pro-inflammatory mediators in intestinal, extra-intestinal and systemic organs to naive levels and furthermore, resulted in distinct shifts in the fecal microbiota composition. In conclusion, our preclinical placebo-controlled intervention study provides evidence that therapeutic carvacrol application constitutes a promising option to alleviate campylobacteriosis in the infected vertebrate host.