The mechanisms and safety of probiotics against toxigenic <i>clostridium difficile</i>

Liu, Dianbin; Zeng, Lingbing; Yan, Zhihan; Jia, Junqi; Gao, Jing; Wei, Yijun

doi:10.1080/14787210.2020.1778464

Cited by 11 publications

(9 citation statements)

References 96 publications

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“…Toxigenic C. difficile is the main cause of antibioticassociated diarrhea, and the resulting infection (C. difficile infection, CDI) is potentially fatal (Janoir, 2016). The use of kefir-derived microorganisms as an alternative treatment and prevention agent against CDI has been studied in vitro and in vivo (Liu et al, 2020). Banerjee et al (2009) reported that L. delbrueckii ssp.…”

Section: Antimicrobial Propertiesmentioning

confidence: 99%

Invited review: Milk kefir microbiota—Direct and indirect antimicrobial effects

González‐Orozco

García‐Cano

Jiménez-Flores

et al. 2022

Journal of Dairy Science

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Kefir is a fermented dairy product with well recognized probiotic properties. Recently, consumer interest in fermented products with probiotic microorganisms has increased due to the accumulating evidence of the effects of kefir microorganisms on the modulation of gut microbiota and their antimicrobial activity. Although the health properties of kefir have been reviewed in other works, the present review addresses the antimicrobial effects of kefir microbiota and associated compounds. The antimicrobial activity of kefir microorganisms could derive from different mechanisms. The microorganisms' capacity to adhere to the intestinal epithelium, preventing the adhesion of pathogens, and their immunomodulation properties are among the mechanisms suggested. Bacteria and yeast isolated from kefir have been shown to have in vivo and in vitro antimicrobial activity against enteropathogenic bacteria and spoilage fungi. However, most reports have focused their approach on single-strain antimicrobial properties; evaluation of antimicrobial activity of cocultures of kefir microbiota and their potential mechanisms of action has been neglected. Kefir microbiota and associated compounds have shown promising antimicrobial effects; however, more research needs to be done to discern the mechanisms of action.

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Section: Antimicrobial Propertiesmentioning

confidence: 99%

Invited review: Milk kefir microbiota—Direct and indirect antimicrobial effects

González‐Orozco

García‐Cano

Jiménez-Flores

et al. 2022

Journal of Dairy Science

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“…In this context, probiotics can, at least on paper, be effective in restoring the intestinal dysbiosis and play a protective role against CDI ( Na and Kelly, 2011 ). Although Saccharomyces, Bifidobacterium, and Lactobacillus genera all carried a protective effect against C. difficile ( Mills et al, 2018 ; Liu et al, 2020 ), the efficacy of probiotics for CDI prevention and/or treatment is currently limited. In keeping with this, we observed only a modest and not a significant effect in limiting the histopathological damage and regulating the epithelial tight junction protein expression of ZO-1 and occludin, following preventive administration of pLP in our murine model.…”

Section: Discussionmentioning

confidence: 99%

A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis

et al. 2021

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Genetically engineered probiotics, able to in situ deliver therapeutically active compounds while restoring gut eubiosis, could represent an attractive therapeutic alternative in Clostridium difficile infection (CDI). Palmitoylethanolamide is an endogenous lipid able to exert immunomodulatory activities and restore epithelial barrier integrity in human models of colitis, by binding the peroxisome proliferator–activated receptor-α (PPARα). The aim of this study was to explore the efficacy of a newly designed PEA-producing probiotic (pNAPE-LP) in a mice model of C. difficile toxin A (TcdA)-induced colitis. The human N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), a key enzyme involved in the synthesis of PEA, was cloned and expressed in a Lactobacillus paracasei that was intragastrically administered to mice 7 days prior the induction of the colitis. Bacteria carrying the empty vector served as negative controls (pLP).In the presence of palmitate, pNAPE-LP was able to significantly increase PEA production by 27,900%, in a time- and concentration-dependent fashion. Mice treated with pNAPE-LP showed a significant improvement of colitis in terms of histological damage score, macrophage count, and myeloperoxidase levels (−53, −82, and −70.4%, respectively). This was paralleled by a significant decrease both in the expression of toll-like receptor-4 (−71%), phospho-p38 mitogen-activated protein kinase (−72%), hypoxia-inducible factor-1-alpha (−53%), p50 (−74%), and p65 (−60%) and in the plasmatic levels of interleukin-6 (−86%), nitric oxide (−59%), and vascular endothelial growth factor (−71%). Finally, tight junction protein expression was significantly improved by pNAPE-LP treatment as witnessed by the rescue of zonula occludens-1 (+304%), Ras homolog family member A-GTP (+649%), and occludin expression (+160%). These protective effects were mediated by the specific release of PEA by the engineered probiotic as they were abolished in PPARα knockout mice and in wild-type mice treated with pLP. Herein, we demonstrated that pNAPE-LP has therapeutic potential in CDI by inhibiting colonic inflammation and restoring tight junction protein expression in mice, paving the way to next generation probiotics as a promising strategy in CDI prevention.

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“…Instead, the reader is referred to recent reviews on this topic. 27–30 In future research, robust, randomized, controlled clinical trials (with defined probiotic strain or combination of strains at appropriate doses) are needed to fill the scientific gaps regarding the potential protective effect of probiotics on CDI. Confirmatory studies with the same strains and a risk-benefit analysis should be performed.…”

Section: Administration Of Microbes For Targeted Microbiota Modificationmentioning

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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The mechanisms and safety of probiotics against toxigenic clostridium difficile

Cited by 11 publications

References 96 publications

Invited review: Milk kefir microbiota—Direct and indirect antimicrobial effects

Invited review: Milk kefir microbiota—Direct and indirect antimicrobial effects

A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis

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

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