Non-toxigenic strain of Clostridioides difficile Z31 reduces the occurrence of C. difficile infection (CDI) in one-day-old piglets on a commercial pig farm

Júnior, Carlos Augusto de Oliveira; Silva, Rodrigo; Lage, Andrey Pereira; Coura, Fernanda Morcatti; Ramos, Carolina Pantuzza; Alfieri, Amauri Alcindo; Guedes, Roberto Maurício Carvalho; Lobato, Francisco Carlos Faria

doi:10.1016/j.vetmic.2019.02.026

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…Furthermore, the protection was lost when the colonizing NTCD was removed using vancomycin before the challenge (Borriello and Barclay, 1985). Since then, a variety of animal models have shown that non-toxigenic strains can colonize the GIT and protect against TCD -mediated disease (Borriello and Barclay, 1985;Sambol et al, 2003;Nagaro et al, 2013;de Oliveira Júnior et al, 2016;Oliveira Júnior et al, 2019;Leslie et al, 2021). The first human clinical trial was performed in 1980s where two patients suffering from rCDI were treated with NTCD-M1 strain after vancomycin administration with a 50% clinical success rate (Seal et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Host Immune Responses to Clostridioides difficile: Toxins and Beyond

et al. 2021

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Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CDI have urged the medical community to search for novel treatment options. Strains that do not produce toxins, so called non-toxigenic C. difficile, have been known to colonize the colon and protect the host against CDI. In this review, a comprehensive description and comparison of the immune responses to toxigenic C. difficile and non-toxigenic adherence, and colonization factors, here called non-toxin proteins, is provided. This revealed a number of similarities between the host immune responses to toxigenic C. difficile and non-toxin proteins, such as the influx of granulocytes and the type of T-cell response. Differences may reflect genuine variation between the responses to toxigenic or non-toxigenic C. difficile or gaps in the current knowledge with respect to the immune response toward non-toxigenic C. difficile. Toxin-based and non-toxin-based immunization studies have been evaluated to further explore the role of B cells and reveal that plasma cells are important in protection against CDI. Since the success of toxin-based interventions in humans to date is limited, it is vital that future research will focus on the immune responses to non-toxin proteins and in particular non-toxigenic strains.

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Section: Introductionmentioning

confidence: 99%

Host Immune Responses to Clostridioides difficile: Toxins and Beyond

et al. 2021

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“…NTCD strains offer significant potential as therapeutic interventions for CDI [ 20 , 21 , 24 ]. The success of NTCD in preventing CDI has been demonstrated previously in the hamster model [ 20 , 21 ], in neonatal piglets [ 63 ], and also in humans in the treatment of recurrent CDI [ 24 ]. Furthermore, NTCD has been demonstrated in Phase I clinical trials to be well tolerated and safe [ 64 ], and it is also able to significantly reduce recurrent CDI from 30% in placebo group versus 11% (10 4 spore dose) and 5% (10 7 spore dose) alongside concurrent antimicrobial therapy in a Phase II randomized clinical trial [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model

et al. 2023

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Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI.

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“…Hammer et al [10] documented an increase of neutralizing antitoxins against C. perfringens type A in piglets born from vaccinated dams compared to those born of dams not vaccinated, and Richard et al [12] reported higher titres against C. perfringens type C in vaccinated piglets when compared to those not vaccinated. Finally, in the study by Oliveira et al [11], the authors documented a reduction of the isolation of C. perfringens in diarrhoea samples after administering a non-toxigenic strain of C. difficile to one-day-old piglets on a commercial pig farm.…”

Section: Clostridium Perfringensmentioning

confidence: 97%

“…Of the vaccination studies, two of them tested sow and gilt vaccination strategies to control necrotizing enteritis (C. perfringens type C; [9]) and C. perfringens type A-associated diarrhoea in piglets [10]. Two other studies assessed the efficacy of piglet vaccination to control neonatal diarrhoea caused by Clostridioides difficile [11] and necrotizing enteritis (C. perfringens type C; [12]).…”

Section: Clostridium Perfringensmentioning

confidence: 99%

A Systematic Review on the Effectiveness of Pre-Harvest Meat Safety Interventions in Pig Herds to Control Salmonella and Other Foodborne Pathogens

et al. 2021

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This systematic review aimed to assess the effectiveness of pre-harvest interventions to control the main foodborne pathogens in pork in the European Union. A total of 1180 studies were retrieved from PubMed® and Web of Science for 15 pathogens identified as relevant in EFSA’s scientific opinion on the public health hazards related to pork (2011). The study selection focused on controlled studies where a cause–effect could be attributed to the interventions tested, and their effectiveness could be inferred. Altogether, 52 studies published from 1983 to 2020 regarding Campylobacter spp., Clostridium perfringens, Methicillin-resistant Staphylococcus aureus, Mycobacterium avium, and Salmonella spp. were retained and analysed. Research was mostly focused on Salmonella (n = 43 studies). In-feed and/or water treatments, and vaccination were the most tested interventions and were, overall, successful. However, the previously agreed criteria for this systematic review excluded other effective interventions to control Salmonella and other pathogens, like Yersinia enterocolitica, which is one of the most relevant biological hazards in pork. Examples of such successful interventions are the Specific Pathogen Free herd principle, stamping out and repopulating with disease-free animals. Research on other pathogens (i.e., Hepatitis E, Trichinella spiralis and Toxoplasma gondii) was scarce, with publications focusing on epidemiology, risk factors and/or observational studies. Overall, high herd health coupled with good management and biosecurity were effective to control or prevent most foodborne pathogens in pork at the pre-harvest level.

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Non-toxigenic strain of Clostridioides difficile Z31 reduces the occurrence of C. difficile infection (CDI) in one-day-old piglets on a commercial pig farm

Cited by 6 publications

References 44 publications

Host Immune Responses to Clostridioides difficile: Toxins and Beyond

Host Immune Responses to Clostridioides difficile: Toxins and Beyond

Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model

A Systematic Review on the Effectiveness of Pre-Harvest Meat Safety Interventions in Pig Herds to Control Salmonella and Other Foodborne Pathogens

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