Nature-Identical Compounds and Organic Acids Ameliorate and Prevent the Damages Induced by an Inflammatory Challenge in Caco-2 Cell Culture

Toschi, Andrea; Rossi, Barbara; Tugnoli, Benedetta; Piva, Andrea; Grilli, Ester

doi:10.3390/molecules25184296

Cited by 20 publications

(18 citation statements)

References 43 publications

(55 reference statements)

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“…But the complex nature of the colonization process requires a tailored combination of in vitro evidence combined in vivo data so the effects of these mixed antimicrobials can be understood and utilized as part of a One Health approach to improving animal health. Previously it has been suggested that combinations of antimicrobials, rather than single compounds, were more efficient in controlling bacterial infections 47 and our study demonstrates that synergistic effects can be also occur against parasitic infections in vitro and in vivo. Results suggest that mixtures of natural antimicrobials can: (1) modulate the host immune response, (2) reduce parasite-induced host oxidative events, and (3) alleviate clinical signs and growth inhibition associated with coccidiosis.…”

Section: Discussionsupporting

confidence: 66%

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis

Balta

Marcu

Linton

et al. 2021

Sci Rep

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Eimeria tenella and Eimeria bovis are complex parasites responsible for the condition of coccidiosis, that invade the animal gastrointestinal intestinal mucosa causing severe diarrhoea, loss of appetite or abortions, with devastating impacts on the farming industry. The negative impacts of these parasitic infections are enhanced by their role in promoting the colonisation of the gut by common foodborne pathogens. The aim of this study was to test the anti-Eimeria efficacy of maltodextrin, sodium chloride, citric acid, sodium citrate, silica, malic acid, citrus extract, and olive extract individually, in vitro and in combination, in vivo. Firstly, in vitro infection models demonstrated that antimicrobials reduced (p < 0.05), both singly and in combination (AG), the ability of E. tenella and E. bovis to infect MDBK and CLEC-213 epithelial cells, and the virulence reduction was similar to that of the anti-coccidial drug Robenidine. Secondly, using an in vivo broiler infection model, we demonstrated that AG reduced (p = 0.001) E. tenella levels in the caeca and excreted faeces, reduced inflammatory oxidative stress, improved the immune response through reduced ROS, increased Mn-SOD and SCFA levels. Levels of IgA and IgM were significantly increased in caecal tissues of broilers that received 0.5% AG and were associated with improved (p < 0.0001) tissue lesion scores. A prophylactic approach increased the anti-parasitic effect in vivo, and results indicated that administration from day 0, 5 and 10 post-hatch reduced tissue lesion scores (p < 0.0001) and parasite excretion levels (p = 0.002). Conclusively, our in vitro and in vivo results demonstrate that the natural antimicrobial mixture (AG) reduced parasitic infections through mechanisms that reduced pathogen virulence and attenuated host inflammatory events.

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Section: Discussionsupporting

confidence: 66%

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis

Balta

Marcu

Linton

et al. 2021

Sci Rep

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“…Organic acids (e.g. citrus extracts) have been shown to reduce the generation of reactive oxygen species thereby preventing oxidative cell injury [ 34 ] and when used in combinations will restore TEER and improve cellular tight junctions [ 26 ]. The Auraguard-catalysed reduction in H 2 O 2 released by the infected MDCK cells was linked to the observed increased expression of the ZO-1 protein.…”

Section: Discussionmentioning

confidence: 99%

“…The quantification of zonula occludens-1 (ZO-1) and occluding expression was performed as previously described with small modifications [ 26 ]. Briefly, the exposed or infected MDCK cells were snap-frozen in liquid nitrogen until use.…”

Section: Methodsmentioning

confidence: 99%

“…Natural antimicrobials can serve as both treatment and prophylaxis by preventing a drop in trans-epithelial resistance and restoring cellular TJ integrity [ 26 ]. The present study investigated the possible role of natural antimicrobials and their anti-pathogenic effect against C. jejuni RC039, S. enterica SE 10/72 and C. perfringens ATCC® 13124 in canine derived Madin–Darby Canine Kidney cells (MDCK).…”

Section: Introductionmentioning

confidence: 99%

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Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells

et al. 2021

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Background The classification of natural antimicrobials as potential antibiotic replacements is still hampered by the absence of clear biological mechanisms behind their mode of action. This study investigated the mechanisms underlying the anti-bacterial effect of a mixture of natural antimicrobials (maltodextrin, citric acid, sodium citrate, malic acid, citrus extract and olive extract) against Campylobacter jejuni RC039, Salmonella enterica SE 10/72 and Clostridium perfringens ATCC® 13124 invasion of Madin–Darby Canine Kidney cells (MDCK). Results Minimum sub-inhibitory concentrations were determined for Campylobacter jejuni (0.25%), Salmonella enterica (0.50%) and Clostridium perfringens (0.50%) required for the in vitro infection assays with MDCK cells. The antimicrobial mixture significantly reduced the virulence of all three pathogens towards MDCK cells and restored the integrity of cellular tight junctions through increased transepithelial resistance (TEER) and higher expression levels of ZO-1 (zonula occludens 1) and occludin. This study also identified the ERK (external regulated kinase) signalling pathway as a key mechanism in blocking the pro-inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α) in infected cells. The reduction in hydrogen peroxide (H2O2) production and release by infected MDCK cells, in the presence of the antimicrobial mixture, was also associated with less tetrathionate formed by oxidation of thiosulphate (p < 0.0001). Conclusion The present study describes for the first time that mixtures of natural antimicrobials can prevent the formation of substrates used by bacterial pathogens to grow and survive in anaerobic environments (e.g. tetrathionate). Moreover, we provide further insights into pathogen invasion mechanisms through restoration of cellular structures and describe their ability to block the ERK–MAPK kinase pathway responsible for inflammatory cytokine release

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“…Unfortunately, the potential beneficial effects on epithelial cells of medium-chain fatty acids are not fully understood yet. Toschi et al (2020) reported also beneficial effects of citric acid on the epithelial barrier function and tight junction gene expression in vitro. Bacitracin is an antimicrobial agent, used to control NE in poultry.…”

Section: Introductionmentioning

confidence: 90%

A mixture of organic acids and thymol protects primary chicken intestinal epithelial cells from Clostridium perfringens infection in vitro

et al. 2022

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Nature-Identical Compounds and Organic Acids Ameliorate and Prevent the Damages Induced by an Inflammatory Challenge in Caco-2 Cell Culture

Cited by 20 publications

References 43 publications

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis

Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells

A mixture of organic acids and thymol protects primary chicken intestinal epithelial cells from Clostridium perfringens infection in vitro

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