Diarrheal Mechanisms and the Role of Intestinal Barrier Dysfunction in Campylobacter Infections

Sá, Fábia Daniela Lobo de; Schulzke, Jörg–Dieter; Bücker, Roland

doi:10.1007/978-3-030-65481-8_8

Cited by 22 publications

(13 citation statements)

References 160 publications

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“…Nevertheless, administration of the pre-hormone VD protects against C. jejuni-induced epithelial barrier dysfunction in vitro and in vivo. VD should therefore be considered as a potentially useful therapeutic supplement, when combined with other barrier-protective, immunomodulatory, and anti-inflammatory compounds, such as curcumin or resveratrol [3,45,46], for prevention and treatment of acute and chronic gastrointestinal disorders.…”

Section: Jejuni Interference With the Vitamin D Pathwaymentioning

confidence: 99%

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Sá

Backert

Nattramilarasu

et al. 2021

IJMS

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Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10−/− mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.

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Section: Jejuni Interference With the Vitamin D Pathwaymentioning

confidence: 99%

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Sá

Backert

Nattramilarasu

et al. 2021

IJMS

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“…Apart from the increase in microbial diversity, PT also inhibited the abnormal proliferation of several conditioned pathogens in the cecum of the TM-exposed piglets. For instance, Campylobacter and Veillonella are detrimental to intestinal barrier function, and their relative abundance is positively related to the risk of intestinal diseases such as diarrhea. − In addition, Actinobacillus is found to be enriched in the gut of piglets infected with epidemic diarrhea virus with an inhibitory role on intestinal energy and amino acid metabolism . In this study, the relative abundance of Campylobacter , Veillonella , and Actinobacillus was significantly reduced by PT treatment.…”

Section: Discussionmentioning

confidence: 54%

Pterostilbene Prevents Tunicamycin-Induced Intestinal Barrier Damage by Targeting Endoplasmic Reticulum Stress, Oxidative Stress, Autophagy, and Gut Microbiota

Chen

Wang

et al. 2022

J. Agric. Food Chem.

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Endoplasmic reticulum (ER) stress is a crucial factor in the pathogenesis of intestinal diseases. Pterostilbene (PT) has been demonstrated to mitigate ER stress and protect against intestinal disorders. Here, we investigated the effects of PT on tunicamycin (TM)-induced intestinal ER stress and intestinal barrier damage in vivo in piglets and in vitro in intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cells. Results indicated that PT prevented TM-induced body weight loss (−0.67 ± 0.16 vs −0.48 ± 0.08 kg) and improved intestinal barrier integrity and goblet cell function of the TM-challenged piglets (P < 0.05). PT also inhibited ER stress, restored redox homeostasis and autophagic flux, and decreased apoptosis in the TM-challenged jejunum and the TM-exposed IPEC-J2 cells (P < 0.05). However, these attenuating effects of PT in the TM-treated IPEC-J2 cells were blunted by the knockdown of sirtuin 1 (P < 0.05). Moreover, PT increased the Ace index (390.12 ± 60.05 vs 460.27 ± 42.83) and downregulated the prevalence of the phylum Proteobacteria (48.73% ± 12.62% vs 32.10% ± 11.08%) of cecal microbiota of the TM-challenged piglets (P < 0.05). In conclusion, PT alleviated TM-induced intestinal barrier damage by regulating ER homeostasis, oxidative stress, autophagic flux, and gut microbiota.

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“…The major role of LOS in C. jejuni-mediated intestinal pathogenesis was further supported recently by independent findings in humans (Bücker et al, 2018) and in various murine models of campylobacteriosis (reviewed by Mousavi et al, 2020). The downward spiral in the infected intestinal mucosa includes the innate immune activation including subepithelial macrophages and granulocytes (a mucosal cytokine storm), which in turn aggravates epithelial leakage, which leads again to further influx of antigens (Butkevych et al, 2020;Lobo de Sá et al, 2021). The so-called leaky gut phenomenon is the model representation for this cytokine-induced barrier impairment (Hollander, 1999;Schulzke et al, 2006).…”

Section: Introductionmentioning

confidence: 84%

Resveratrol Prevents Campylobacter jejuni-Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway

et al. 2021

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Campylobacter jejuni is a bacterial human pathogen causing gastroenteritis and sequelae like irritable bowel syndrome. Epidemiologists count the human campylobacteriosis by C. jejuni as the most common foodborne zoonosis and bacterial diarrheal disease worldwide. Based on bioinformatics predictions for potential protective compounds in campylobacteriosis, the question was raised whether the plant-based polyphenol resveratrol is sufficient to attenuate intestinal epithelial damage induced by C. jejuni. We investigated this by performing experimental infection studies in an epithelial cell culture and the secondary abiotic IL-10−/− mouse model. In C. jejuni-infected human colonic HT-29/B6 cell monolayers, transepithelial electrical resistance (TER) was decreased and the paracellular marker flux of fluorescein (332 Da) increased. Concomitantly, the tight junction (TJ) proteins occludin and claudin-5 were re-distributed off the tight junction domain. This was accompanied by an increased induction of epithelial apoptosis, both changes contributing to compromised barrier function and the opening of the leak pathway induced by C. jejuni. In parallel, the recovery experiments with the application of resveratrol revealed a functional improvement of the disturbed epithelial barrier in both models in vitro and in vivo. During treatment with resveratrol, TJ localization of occludin and claudin-5 was fully restored in the paracellular domain of HT-29/B6 cells. Moreover, resveratrol decreased the rate of epithelial apoptosis. These resveratrol-induced molecular and cellular effects would therefore be expected to improve epithelial barrier function, thereby minimizing the so-called leaky gut phenomenon. In conclusion, the induction of the leak pathway by C. jejuni and the restoration of barrier function by resveratrol demonstrates its effectiveness as a potential preventive or therapeutic method of mitigating the leaky gut associated with campylobacteriosis.

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Diarrheal Mechanisms and the Role of Intestinal Barrier Dysfunction in Campylobacter Infections

Cited by 22 publications

References 160 publications

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Pterostilbene Prevents Tunicamycin-Induced Intestinal Barrier Damage by Targeting Endoplasmic Reticulum Stress, Oxidative Stress, Autophagy, and Gut Microbiota

Resveratrol Prevents Campylobacter jejuni-Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway

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