Pediococcus pentosaceus IM96 Exerts Protective Effects against Enterohemorrhagic Escherichia coli O157:H7 Infection In Vivo

Enterohemorrhagic Escherichia coli (EHEC) is a notorious and prevalent foodborne pathogen which can cause serious intestinal diseases. The antagonistic activity of probiotics against EHEC is promising, but most of the studies concerning this subject have been carried out in vitro. Specifically, the interaction between Pediococcus pentosaceus and EHEC O157:H7 in vivo has not been reported yet. In this study, we investigated the protective effect of P. pentosaceus IM96 on EHEC O157:H7-infected female mice in vivo. The results demonstrated that P. pentosaceus IM96 reduced the level of pro-inflammatory factors and increased the level of anti-inflammatory factors of EHEC O157:H7-infected mice. Furthermore, P. pentosaceus IM96 alleviated intestinal mucosal damage and increased the level of MUC-2, tight junction (TJ) proteins, and short chain fatty acids (SCFAs). The intestinal microbial community structure and the diversity and richness of the microbiota were also changed by P. pentosaceus IM96 treatment. In summary, P. pentosaceus IM96 exerted protective effects against EHEC O157:H7 via alleviating intestinal inflammation, strengthening the intestinal barrier function, and regulating intestinal microbiota, suggesting that P. pentosaceus IM96 might serve as a potential microbial agent to prevent and treat intestinal diseases caused by EHEC O157:H7 infection in the future.

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The Protective Effects of 2’-Fucosyllactose Against E. Coli O157 Infection Are Mediated by the Regulation of Gut Microbiota and the Inhibition of Pathogen Adhesion

Nutrients ◽

10.3390/nu12051284 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1284 ◽

Cited By ~ 2

Author(s):

Yuanyifei Wang ◽

Yan Zou ◽

Jin Wang ◽

Hui Ma ◽

Bowei Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Foodborne Pathogen ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Intestinal Barrier Function ◽

Protective Effects ◽

E Coli ◽

Beneficial Effects

As the richest component in human milk oligosaccharides (HMOs), 2’-fucosyllactose (2’-FL) can reduce the colonization of harmful microbiota in vivo, thus lowering the risk of infection; however, the mechanism for this is still unclear. In this study, a model of Escherichia coli O157 infection in healthy adult mice was established to explore the effect of 2’-FL intervention on E. coli O157 colonization and its protective effects on mice. The results showed that 2’-FL intake reduced E. coli O157 colonization in mice intestine by more than 90% (p < 0.001), and it also reduced intestinal inflammation, increased the content of fecal short-chain fatty acids, and enhanced intestinal barrier function. These beneficial effects were attributed to the increased expression of mucins such as MUC2 (increased by more than 20%, p < 0.001), and inhibition of E. coli O157 cell adhesion (about 30% reduction, p < 0.001), and were associated with the modulation of gut microbiota composition. 2’-FL significantly increased the abundance of Akkermansia, a potential probiotic, which may represent the fundamental means by which 2’-FL enhances the expression of mucin and reduces the colonization of harmful bacteria. The current study may support the use of 2’-FL in the prevention of foodborne pathogen infections in human.

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Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00596-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yueqin Qiu ◽

Jun Yang ◽

Li Wang ◽

Xuefen Yang ◽

Kaiguo Gao ◽

...

Keyword(s):

Gut Microbiota ◽

Oxidative Damage ◽

Protein Expression ◽

Intestinal Inflammation ◽

Control Diet ◽

Intestinal Barrier Function ◽

Protective Effects ◽

Gut Health ◽

Antioxidant Genes ◽

Mrna And Protein Expression

Abstract Background Deoxynivalenol (DON) is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals. Resveratrol (RES) effectively exerts anti-inflammatory and antioxidant effects. However, the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear. Therefore, this study aimed to investigate the effect of RES on growth performance, gut health and the gut microbiota in DON-challenged piglets. A total of 64 weaned piglets [Duroc × (Landrace × Yorkshire), 21-d-old, 6.97 ± 0.10 kg body weight (BW)] were randomly allocated to 4 treatment groups (8 replicate pens per treatment, each pen containing 2 males; n = 16 per treatment) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. Results DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) mRNA and protein expression, and increased zonula occludens-1 (ZO-1) mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet (P < 0.05). Compared with unsupplemented DON-challenged piglets, infected piglets fed a diet with RES showed significantly decreased malondialdehyde (MDA) levelsand increased mRNA expression of antioxidant enzymes and antioxidant genes (i.e., GCLC, GCLM, HO-1, SOD1 and NQO-1) and glutamate-cysteine-ligase modulatory subunit (GCLM) protein expression (P < 0.05). Moreover, RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets (P < 0.05). Finally, RES supplementation significantly increased the abundance of Roseburia and butyrate concentrations, while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone (P < 0.05). Conclusions RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function, alleviating intestinal inflammation and oxidative damage, and positively modulating the gut microbiota. The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations, and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.

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Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine ◽

10.1186/s10020-021-00332-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jian-Ping Zhang ◽

Wei-Jing Zhang ◽

Miao Yang ◽

Hua Fang

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

Scientific Reports ◽

10.1038/srep38480 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 27

Author(s):

Guo Zu ◽

Jing Guo ◽

Ningwei Che ◽

Tingting Zhou ◽

Xiangwen Zhang

Keyword(s):

Signaling Pathway ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Ginsenoside Rg1 ◽

Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

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Effect of Lactobacillus acidophilus Fermented Broths Enriched with Eruca sativa Seed Extracts on Intestinal Barrier and Inflammation in a Co-Culture System of an Enterohemorrhagic Escherichia coli and Human Intestinal Cells

Nutrients ◽

10.3390/nu12103064 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3064

Author(s):

Francesca Bonvicini ◽

Eleonora Pagnotta ◽

Angela Punzo ◽

Donato Calabria ◽

Patrizia Simoni ◽

...

Keyword(s):

Escherichia Coli ◽

Beneficial Effect ◽

Culture System ◽

Intestinal Inflammation ◽

Enterohemorrhagic Escherichia Coli ◽

Eruca Sativa ◽

Intestinal Function ◽

Barrier Dysfunction ◽

Gut Barrier ◽

Seed Extracts

Lactic acid bacteria (LAB) “fermentates” confer a beneficial effect on intestinal function. However, the ability of new fermentations to improve LAB broth activity in preventing pathogen-induced intestinal inflammation and barrier dysfunction has not yet been studied. The objective of this study was to determine if broths of LAB fermented with Eruca sativa or Barbarea verna seed extracts prevent gut barrier dysfunction and interleukin-8 (CXCL8) release in vitro in human intestinal Caco-2 cells infected with enterohemorrhagic Escherichia coli (EHEC) O157:H7. LAB broths were assayed for their effects on EHEC growth and on Caco-2 viability; thereafter, their biological properties were analysed in a co-culture system consisting of EHEC and Caco-2 cells. Caco-2 cells infected with EHEC significantly increased CXCL8 release, and decreased Trans-Epithelial Electrical Resistance (TEER), a barrier-integrity marker. Notably, when Caco-2 cells were treated with LAB broth enriched with E. sativa seed extract and thereafter infected, both CXCL8 expression and epithelial dysfunction reduced compared to in untreated cells. These results underline the beneficial effect of broths from LAB fermented with E. sativa seed extracts in gut barrier and inflammation after EHEC infection and reveal that these LAB broths can be used as functional bioactive compounds to regulate intestinal function.

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Identification of Antibiotics That Diminish Disease in a Murine Model of Enterohemorrhagic Escherichia coli Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02159-19 ◽

2020 ◽

Vol 64 (4) ◽

Cited By ~ 1

Author(s):

Sabrina Mühlen ◽

Isabell Ramming ◽

Marina C. Pils ◽

Martin Koeppel ◽

Jana Glaser ◽

...

Keyword(s):

Escherichia Coli ◽

Enterohemorrhagic Escherichia Coli ◽

Content Type ◽

Shiga Toxins ◽

Escherichia Coli Infection ◽

Uremic Syndrome ◽

Severity Of The Disease ◽

Selection Of ◽

Mild Diarrhea

ABSTRACT Infections with enterohemorrhagic Escherichia coli (EHEC) cause disease ranging from mild diarrhea to hemolytic-uremic syndrome (HUS) and are the most common cause of renal failure in children in high-income countries. The severity of the disease derives from the release of Shiga toxins (Stx). The use of antibiotics to treat EHEC infections is generally avoided, as it can result in increased stx expression. Here, we systematically tested different classes of antibiotics and found that their influence on stx expression and release varies significantly. We assessed a selection of these antibiotics in vivo using the Citrobacter rodentium ϕstx2dact mouse model and show that stx2d-inducing antibiotics resulted in weight loss and kidney damage despite clearance of the infection. However, several non-Stx-inducing antibiotics cleared bacterial infection without causing Stx-mediated pathology. Our results suggest that these antibiotics might be useful in the treatment of EHEC-infected human patients and decrease the risk of HUS development.

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Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽

10.1155/2019/2601408 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Jie Yan ◽

Si-Chi Xu ◽

Chun-Yan Kong ◽

Xiao-Yang Zhou ◽

Zhou-Yan Bian ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Injury ◽

Inflammatory Factors ◽

Peroxisome Proliferator ◽

Protective Effects ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ ◽

Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

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The Locus of Enterocyte Effacement-Encoded Effector Proteins All Promote Enterohemorrhagic Escherichia coli Pathogenicity in Infant Rabbits

Infection and Immunity ◽

10.1128/iai.73.3.1466-1474.2005 ◽

2005 ◽

Vol 73 (3) ◽

pp. 1466-1474 ◽

Cited By ~ 60

Author(s):

Jennifer M. Ritchie ◽

Matthew K. Waldor

Keyword(s):

Escherichia Coli ◽

Effector Proteins ◽

Enterohemorrhagic Escherichia Coli ◽

Lesion Formation ◽

Specific Effects ◽

Genes Encoding ◽

Organ Specific ◽

Rabbit Intestine ◽

Enterocyte Effacement

ABSTRACT The genes encoding the enterohemorrhagic Escherichia coli (EHEC) type III secretion system (TTSS) and five effector proteins secreted by the TTSS are located on the locus of enterocyte effacement (LEE) pathogenicity island. Deletion of tir, which encodes one of these effector proteins, results in a profound reduction (∼10,000-fold) in EHEC colonization of the infant rabbit intestine, but the in vivo phenotypes of other LEE genes are unknown. Here, we constructed in-frame deletions in escN, the putative ATPase component of the TTSS, and the genes encoding the four other LEE-encoded effector proteins, EspH, Map, EspF, and EspG, to investigate the contributions of the TTSS and the translocated effector proteins to EHEC pathogenicity in infant rabbits. We found that the TTSS is required for EHEC colonization and attaching and effacing (A/E) lesion formation in the rabbit intestine. Deletion of escN reduced EHEC recovery from the rabbit intestine by ∼10,000-fold. Although EspH, Map, EspF, and EspG were not required for A/E lesion formation in the rabbit intestine or in HeLa cells, these effector proteins promote EHEC colonization. Colonization by the espH and espF mutants was reduced throughout the intestine. In contrast, colonization by the map and espG mutants was reduced only in the small intestine, indicating that Map and EspG have organ-specific effects. EspF appears to down-regulate the host response to EHEC, since we observed increased accumulation of polymorphonuclear leukocytes in the colonic mucosa of rabbits infected with the EHEC espF mutant. Thus, all the known LEE-encoded effector proteins influence EHEC pathogenicity.

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Shiga Toxin Gene Loss and Transfer In Vitro and In Vivo during Enterohemorrhagic Escherichia coli O26 Infection in Humans

Applied and Environmental Microbiology ◽

10.1128/aem.02937-06 ◽

2007 ◽

Vol 73 (10) ◽

pp. 3144-3150 ◽

Cited By ~ 140

Author(s):

Martina Bielaszewska ◽

Rita Prager ◽

Robin Köck ◽

Alexander Mellmann ◽

Wenlan Zhang ◽

...

Keyword(s):

Escherichia Coli ◽

Shiga Toxin ◽

Gene Loss ◽

Pulsed Field Gel Electrophoresis ◽

Enterohemorrhagic Escherichia Coli ◽

Toxin Gene ◽

Shiga Toxins ◽

E Coli

ABSTRACT Escherichia coli serogroup O26 consists of enterohemorrhagic E. coli (EHEC) and atypical enteropathogenic E. coli (aEPEC). The former produces Shiga toxins (Stx), major determinants of EHEC pathogenicity, encoded by bacteriophages; the latter is Stx negative. We have isolated EHEC O26 from patient stools early in illness and aEPEC O26 from stools later in illness, and vice versa. Intrapatient EHEC and aEPEC isolates had quite similar pulsed-field gel electrophoresis (PFGE) patterns, suggesting that they might have arisen by conversion between the EHEC and aEPEC pathotypes during infection. To test this hypothesis, we asked whether EHEC O26 can lose stx genes and whether aEPEC O26 can be lysogenized with Stx-encoding phages from EHEC O26 in vitro. The stx 2 loss associated with the loss of Stx2-encoding phages occurred in 10% to 14% of colonies tested. Conversely, Stx2- and, to a lesser extent, Stx1-encoding bacteriophages from EHEC O26 lysogenized aEPEC O26 isolates, converting them to EHEC strains. In the lysogens and EHEC O26 donors, Stx2-converting bacteriophages integrated in yecE or wrbA. The loss and gain of Stx-converting bacteriophages diversifies PFGE patterns; this parallels findings of similar but not identical PFGE patterns in the intrapatient EHEC and aEPEC O26 isolates. EHEC O26 and aEPEC O26 thus exist as a dynamic system whose members undergo ephemeral interconversions via loss and gain of Stx-encoding phages to yield different pathotypes. The suggested occurrence of this process in the human intestine has diagnostic, clinical, epidemiological, and evolutionary implications.

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Enterohemorrhagic Escherichia coli Colonization of Human Colonic EpitheliumIn VitroandEx Vivo

Infection and Immunity ◽

10.1128/iai.02928-14 ◽

2014 ◽

Vol 83 (3) ◽

pp. 942-949 ◽

Cited By ~ 35

Author(s):

Steven B. Lewis ◽

Vivienne Cook ◽

Richard Tighe ◽

Stephanie Schüller

Keyword(s):

Escherichia Coli ◽

Human Colon ◽

Enterohemorrhagic Escherichia Coli ◽

Care Needs ◽

T84 Cells ◽

Host Cell Membrane ◽

Content Type ◽

Colonic Biopsy

EnterohemorrhagicEscherichia coli(EHEC) is an important foodborne pathogen causing gastroenteritis and more severe complications, such as hemorrhagic colitis and hemolytic uremic syndrome. Pathology is most pronounced in the colon, but to date there is no direct clinical evidence showing EHEC binding to the colonic epithelium in patients. In this study, we investigated EHEC adherence to the human colon by usingin vitroorgan culture (IVOC) of colonic biopsy samples and polarized T84 colon carcinoma cells. We show for the first time that EHEC colonizes human colonic biopsy samples by forming typical attaching and effacing (A/E) lesions which are dependent on EHEC type III secretion (T3S) and binding of the outer membrane protein intimin to the translocated intimin receptor (Tir). A/E lesion formation was dependent on oxygen levels and suppressed under oxygen-rich culture conditions routinely used for IVOC. In contrast, EHEC adherence to polarized T84 cells occurred independently of T3S and intimin and did not involve Tir translocation into the host cell membrane. Colonization of neither biopsy samples nor T84 cells was significantly affected by expression of Shiga toxins. Our study suggests that EHEC colonizes and forms stable A/E lesions on the human colon, which are likely to contribute to intestinal pathology during infection. Furthermore, care needs to be taken when using cell culture models, as they might not reflect thein vivosituation.

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