Equine hyperimmune serum protects mice against<i>Clostridium difficile</i>spore challenge

Yan, Weiwei; Shin, Kang-Soon; Wang, Shih-Jon; Xiang, Hua; Divers, Thomas J.; McDonough, Sean P.; Bowman, James L.; Rowlands, A G; Akey, Bruce; Mohamed, Hussni; Chang, Yung-Fu

doi:10.4142/jvs.2014.15.2.249

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…All animals had appropriate space, with free access to tap water and a standard rodent diet. The CDI mouse model was induced as previously described (Hutton et al, 2014; Yan et al, 2014) with some modifications. The detailed procedure is shown in Figure 1A.…”

Section: Methodsmentioning

confidence: 99%

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

et al. 2018

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Clostridium difficile is currently the leading cause of nosocomial infection. Antibiotics remain the first-line therapy for C. difficile-associated diseases (CDAD), despite the risks of resistance promotion and further gut microbiota perturbation. Notably, the abundance of Bacteroides fragilis was reported to be significantly decreased in CDAD patients. This study aimed to clarify the prophylactic effects of B. fragilis strain ZY-312 in a mouse model of C. difficile infection (CDI). The CDI mouse model was successfully created using C. difficile strain VPI 10463 spores, as confirmed by lethal diarrhea (12.5% survival rate), serious gut barrier disruption, and microbiota disruption. CDI model mice prophylactically treated with B. fragilis exhibited significantly higher survival rates (100% in low dosage group, 87.5% in high dosage group) and improved clinical manifestations. Histopathological analysis of colon and cecum tissue samples revealed an intact gut barrier with strong ZO-1 and Muc-2 expression. The bacterial diversity and relative abundance of gut microbiota were significantly improved. Interestingly, the relative abundance of Akkermansia muciniphila was positively correlated with B. fragilis treatment. In vitro experiments showed that B. fragilis inhibited C. difficile adherence, and attenuated the decrease in CDI-induced transepithelial electrical resistance, ZO-1 and MUC-2 loss, and apoptosis, suggesting that B. fragilis protected against CDI possibly by resisting pathogen colonization and improving gut barrier integrity and functions. In summary, B. fragilis exerted protective effects on a CDI mouse model by modulating gut microbiota and alleviating barrier destruction, thereby relieving epithelial stress and pathogenic colitis triggered by C. difficile. This study provides an alternative preventative measure for CDI and lays the foundations for further investigations of the relationships among opportunistic pathogens, commensal microbiota, and the gut barrier.

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Section: Methodsmentioning

confidence: 99%

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

et al. 2018

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“…137 Serum from toxoid-immunized horses neutralize TcdA and TcdB in mice challenged with C. difficile spores. 158 However, it is still not known if antibodies produced after natural infection have the same effect.…”

Section: Bacterial Pathogensmentioning

confidence: 99%

Bacterial and viral enterocolitis in horses: a review

et al. 2021

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Enteritis, colitis, and enterocolitis are considered some of the most common causes of disease and death in horses. Determining the etiology of these conditions is challenging, among other reasons because different causes produce similar clinical signs and lesions, and also because some agents of colitis can be present in the intestine of normal animals. We review here the main bacterial and viral causes of enterocolitis of horses, including Salmonella spp., Clostridium perfringens type A NetF-positive, C. perfringens type C, Clostridioides difficile, Clostridium piliforme, Paeniclostridium sordellii, other clostridia, Rhodococcus equi, Neorickettsia risticii, Lawsonia intracellularis, equine rotavirus, and equine coronavirus. Diarrhea and colic are the hallmark clinical signs of colitis and enterocolitis, and the majority of these conditions are characterized by necrotizing changes in the mucosa of the small intestine, colon, cecum, or in a combination of these organs. The presumptive diagnosis is based on clinical, gross, and microscopic findings, and confirmed by detection of some of the agents and/or their toxins in the intestinal content or feces.

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“…The idea of harnessing polyclonal or oligoclonal anti-toxin antibody repertoires to achieve strong toxin neutralization has been explored by several groups. For example, Yan et al 55 produced an antiserum by immunizing horses with inactivated C. difficile spores and TcdA/TcdB toxoids and showed that this antiserum protected mice from CDI in a dose-dependent manner when administered intravenously. Notably, mice receiving the prophylactic antiserum lost less weight, showed no signs of infection, and their weight normalized more rapidly than control animals treated with the preimmune serum.…”

Section: Antibodies and Antibody Alternatives For Neutralization Of C...mentioning

confidence: 99%

New treatment approaches for Clostridioides difficile infections: alternatives to antibiotics and fecal microbiota transplantation

Bratkovič,

Zahirović,

Bizjak

et al. 2024

Gut Microbes

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Clostridioides difficile causes a range of debilitating intestinal symptoms that may be fatal. It is particularly problematic as a hospital-acquired infection, causing significant costs to the health care system. Antibiotics, such as vancomycin and fidaxomicin, are still the drugs of choice for C. difficile infections, but their effectiveness is limited, and microbial interventions are emerging as a new treatment option. This paper focuses on alternative treatment approaches, which are currently in various stages of development and can be divided into four therapeutic strategies. Direct killing of C. difficile (i) includes beside established antibiotics, less studied bacteriophages, and their derivatives, such as endolysins and tailocins. Restoration of microbiota composition and function (ii) is achieved with fecal microbiota transplantation, which has recently been approved, with standardized defined microbial mixtures, and with probiotics, which have been administered with moderate success. Prevention of deleterious effects of antibiotics on microbiota is achieved with agents for the neutralization of antibiotics that act in the gut and are nearing regulatory approval. Neutralization of C. difficile toxins (iii) which are crucial virulence factors is achieved with antibodies/antibody fragments or alternative binding proteins. Of these, the monoclonal antibody bezlotoxumab is already in clinical use. Immunomodulation (iv) can help eliminate or prevent C. difficile infection by interfering with cytokine signaling. Small-molecule agents without bacteriolytic activity are usually selected by drug repurposing and can act via a variety of mechanisms. The multiple treatment options described in this article provide optimism for the future treatment of C. difficile infection.

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Equine hyperimmune serum protects mice againstClostridium difficilespore challenge

Cited by 6 publications

References 41 publications

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

Bacterial and viral enterocolitis in horses: a review

New treatment approaches for Clostridioides difficile infections: alternatives to antibiotics and fecal microbiota transplantation

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