Mechanism of blood-brain barrier disruption by an Escherichia coli from lambs with severe diarrhea and meningoencephalitis

Wang, Weiyu; Cai, Meng-Lu; Hu, Junying; Zhang, Zecai; Wang, Xu; Chang, Xiaoran; Zhang, Fan; Guo, Changming; Wang, Xinping

doi:10.1016/j.micpath.2020.104288

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…The stress caused by the early weaning ( Orgeur et al, 1999 ; Freitas-de-Melo et al, 2022 ) and the difficulties in adapting to the milk substitute due to excessive dosage or inadequate temperature levels increased the number of youngs suffering from diarrhea ( Grosskopf et al, 2017 ; Wang et al, 2019 ). Since the stress of early weaning negatively impacts the immunological status of youngs, it increases the susceptibility to diseases ( Zhang et al, 2018 ), in particular infectious diarrhea ( Skirnisson and Hansson, 2006 ; Fortuoso et al, 2019 ), caused by Escherichia coli ( Wang W. U. et al, 2020 ), border disease virus ( Wang W. U. et al, 2020 ), and parasitic diseases ( Papanikolopoulou et al, 2018 ; Jacobson et al, 2020 ). Diarrhea is at fault for losses to farming enterprises, resulting in goat weight loss, growth retardation, and even death ( Aldomy and Zeid, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea

Zhong

Wang

et al. 2022

Front. Microbiol.

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Early weaning and milk substitutes increase the incidence of diarrhea in young ruminants, which may modify their gut microbiota, metabolism, immunity, and health. The aim of the study was to determine if early weaning and milk substitutes affect the gut microbiota, metabolism, and immunological status of goat kids suffering from diarrhea. The 16S rRNA gene and metagenomic sequencing in feces and serum metabolomics of early-weaned and artificially reared goat kids suffering from diarrhea (DK group) and healthy goat kids reared by their mothers (HK group) were analyzed. The serum biochemistry and immunoglobulin concentration were also determined. Several probiotics, such as Streptococcus and Lactobacillus, were higher in the feces of the DK group than in feces of the HK group. Ruminococcus sp. was elevated in the feces of HKs, likely being a biomarker for goat health. Taking all the carbohydrate-active enzyme (CAZyme) families into consideration, 20 CAZyme families were different between the groups. Compared with the DK group, the relative quantity of glycoside hydrolases (GH) and glycosyltransferase (GT) families in the HK group decreased. GT70 was only identified in HK kids participating in the activity of β-glucuronosyltransferase during the carbohydrate metabolism. Overall, 24 metabolites were different between the groups, which were mainly involved in protein digestion and absorption, cyanoamino acid metabolism, and cholesterol metabolism. The concentrations of immunoglobulins G and M were significantly lower in the DK than in the HK group. In conclusion, our study characterized the fecal microbiota, metabolism, and immunological status of early-weaned and artificially reared goat kids suffering from diarrhea.

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Section: Introductionmentioning

confidence: 99%

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea

Zhong

Wang

et al. 2022

Front. Microbiol.

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“…The miR-223 suppresses NLRP3 expression by binding to its conserved binding site in the 3′UTR of NLRP3 and thus inhibits NLRP3 inflammasome activation ( 41 , 42 ). Considering that NLRP3 has been proved to downregulate the expression of ZO-1, occludin, and claudin-1 in previous studies ( 43 – 46 ), the regulation of miR-223 on TJPs may be accomplished through the targeted regulation of NLRP3. However, it still needs to be clearly proved.…”

Section: Discussion/conclusionmentioning

confidence: 92%

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

Chen

Liang

et al. 2022

Front. Med.

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IntroductionIncreasing evidence supports the idea that the disruption of epithelial tight junction proteins (TJPs) caused by accumulation of uremia toxins, such as homocysteine (Hcy), is one of the most important mechanisms underlying the damage of intestinal barrier function (IBF) in chronic kidney disease (CKD). Since the decrease of hypoxia inducible factor-1α (HIF-1α) is reported to be involved in Hcy-induced cell injury, and the upregulation of microRNA-223 (miR-223) plays a vital protective role in the impairment of IBF in the experimental colitis, we investigated the effect of HIF-1α stabilizer roxadustat on the disruption of TJPs induced by Hcy and CKD and the underlying mechanism.MethodsChronic kidney disease was induced in rats via 5/6 nephrectomy. In a series of experiments, the rats were treated orally with roxadustat of different doses. The expression of tight junction proteins, HIF-1α, and miR-223 was analyzed in different groups by western blotting analysis, RT-qPCR techniques and immunofluorescence. A series of experiments with cultured Caco2 cells was performed.ResultsThe results showed that the expression of TJPs (occludin, claudin-1, and ZO-1) decreased significantly, accompanied by the reduction of HIF-1α and miR-223 in Hcy-treated Caco2 cells and colonic mucosa of uremic rats. The reduction of HIF-1α and miR-223 was reversed by roxadustat and the decrease of TJPs expression was attenuated in both Caco2 cells induced by Hcy and colon tissue of CKD rats. Furthermore, transfection with miR-223 mimics increased the expression of TJPs, while transfection with miR-223 inhibitor decreased their expression in Caco2 cells. MiR-223 inhibitor applied before roxadustat treatment partly diminished the effect of roxadustat on TJPs expression in Caco2 cells.ConclusionThese results indicated that roxadustat attenuated the disruption of epithelial TJPs induced by Hcy in Caco2 cells and the damage of colonic epithelium in CKD rats through the upregulation of miR-223 induced by HIF-1α. A novel insight into the IBF dysfunction in CKD was provided, and it suggests a potential therapeutic use of roxadustat for the IBF dysfunction besides anemia in CKD.

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“…Some studies in animals have explored the role of NLRP3 in bacterial meningitis: It has been reported that the NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis (Hoegen et al, 2011). In addition, E. coli can cause meningoencephalitis by increasing the inflammatory response and activating the TLR2/TLR4/MyD88 and the NLRP3 inflammasome pathways (Wang et al, 2020). NLRP3-deficient mice have decreased systemic inflammatory responses and bacterial outgrowth, which are also associated with an increase in cerebral neutrophil infiltration and cerebral hemorrhages (Geldhoff et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

NLRP3 in the Cerebrospinal Fluid as a Potential Biomarker for the Diagnosis and Prognosis of Community-Acquired Bacterial Meningitis in Adults

Gong

Zhang

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectiveTo discover the levels of NLR family pyrin domain-containing 3 (NLRP3) in the cerebrospinal fluid (CSF) from adult patients with community-acquired bacterial meningitis (CABM).MethodsWe enrolled 34 patients with CABM, 20 patients with viral meningitis (VM), and 25 patients with non-inflammatory neurological disease. Data on standard clinical parameters, scores, and outcomes were obtained from clinical records, and inflammasome levels in the CSF were measured by an enzyme-linked immunosorbent assay. The area under the receiver operating characteristic curve (AUROC) was used to quantify the diagnostic and prognostic performance of CSF NLRP3 as a biomarker of CABM.ResultsThe levels of NLRP3 were elevated in the CSF of patients with CABM, but levels for ASC, caspase-1, or other inflammasomes did not vary significantly. CSF NLRP3 was positively correlated with clinical severity and with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte count, albumin quotient (Qalb), and immunoglobulin G quotient (QIgG). Patients with unfavorable outcomes had higher levels of NLRP3 in the CSF, which were correlated with several blood indicators, including NLR, PLR, and lymphocyte and monocyte counts.ConclusionsOur results suggested that the level of CSF NLRP3 could represent the severity of CABM in adults. CSF NLRP3 may be a good biomarker for the diagnosis of CABM and for the discrimination between CABM and VM. It may also be a better biomarker for predicting the prognosis of adult patients with CABM when compared to the NLR or the lymphocyte and monocyte counts.

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Mechanism of blood-brain barrier disruption by an Escherichia coli from lambs with severe diarrhea and meningoencephalitis

Cited by 9 publications

References 31 publications

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

NLRP3 in the Cerebrospinal Fluid as a Potential Biomarker for the Diagnosis and Prognosis of Community-Acquired Bacterial Meningitis in Adults

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