scholarly journals Autophagy R Educes B Acterial T Ranslocation by Attenuating Oxidative Stress in Hypervirulent Klebsiella Pneumoniae-Caused Liver Abscesses Mice

Author(s):  
Xing Lu ◽  
Xianlong Wang ◽  
Jie Xu ◽  
Chengfen Yin ◽  
Peng Zhang ◽  
...  

Abstract Background Translocation of intestinal flora can cause liver abscesses.The epidemiological data were mainly Kebsiella pneumoniae infection.It is usually associated with changes in mucosal autophagy and oxidative stress.Objective The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of hypervirulent Klebsiella pneumoniae-caused liver abscesses(hvKp-cla) mice model. And the genes that might be involved.Methods C57BL/6J mice were used as study subjects to induce liver abscesses model by hypervirulent Klebsiella pneumoniae gavage. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis.Morphological alterations in the liver and gut were assessed by hematoxylin–eosin staining.Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GPx).In situ hybridization was used to determine whether the bacteria had migrated to the liver.Western blot, RT-PCR,and immunofuorescent staining were preformed to analyze the expression of tight junction and autophagy proteins. The ultrastructural changes of liver were examined by electron microscopy.RNA-seq was used to detect the possible involved genes. Results According to the sequencing analysis, mice were divided into BT (+) group (n = 7) and BT (-) group(n = 7).The damage of intestinal mucosa and liver in BT(+) group was more serious than that in BT(-) group. The translocated Klebsiella pneumoniae was observed in the intestinal mucosa lamina propria and liver.The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (-) group.The expression of LC3II and Beclin1 in BT (-) group was higher than that observed in BT (+). In contrast, BT (+)group had a lower level of Zonulin-1 (ZO-1) and claudin-2. RNA-seq found 1912 genes were up-regulated and 1,911 genes down-regulated. Those genes of mTOR,Atg4b and SERPINA3 were involved. Conclusion Autophagy reduces intestinal hypervirulent Klebsiella pneumoniae translocation by reducing oxidative stress levels. Those genes of mTOR,Atg4b and SERPINA3 were involved.

2015 ◽  
Vol 16 (7) ◽  
pp. 15852-15871 ◽  
Author(s):  
Eleftherios Eleftheriou ◽  
Ioannis-Dimosthenis Adamakis ◽  
Emmanuel Panteris ◽  
Maria Fatsiou

2019 ◽  
Author(s):  
Jianguang Hu ◽  
Xiaoshi Zhong ◽  
Jing Yan ◽  
Daoyuan Zhou ◽  
Danping Qin ◽  
...  

Abstract Background Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy.Methods Patients were recruited during 2017-2019 and divided into healthy control group (CT), CKD non-dialysis group (CKD), hemodialysis group (HD) and peritoneal dialysis group (PD). Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed.Results Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae , Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport.Conclusion Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Hong-Xin Cui ◽  
Ya-Nan Hu ◽  
Jing-Wan Li ◽  
Ke Yuan

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Tingting Hu ◽  
Yinmiao Dong ◽  
Caixia He ◽  
Mingyi Zhao ◽  
Qingnan He

Autism spectrum disorders (ASDs) are a kind of neurodevelopmental disorder with rapidly increasing morbidity. In recent years, many studies have proposed a possible link between ASD and multiple environmental as well as genetic risk factors; nevertheless, recent studies have still failed to identify the specific pathogenesis. An analysis of the literature showed that oxidative stress and redox imbalance caused by high levels of reactive oxygen species (ROS) are thought to be integral parts of ASD pathophysiology. On the one hand, this review aims to elucidate the communications between oxidative stress, as a risk factor, and ASD. As such, there is also evidence to suggest that early assessment and treatment of antioxidant status are likely to result in improved long-term prognosis by disturbing oxidative stress in the brain to avoid additional irreversible brain damage. Accordingly, we will also discuss the possibility of novel therapies regarding oxidative stress as a target according to recent literature. On the other hand, this review suggests a definite relationship between ASD and an unbalanced gastrointestinal tract (GIT) microbiota (i.e., GIT dysbiosis). A variety of studies have concluded that the intestinal microbiota influences many aspects of human health, including metabolism, the immune and nervous systems, and the mucosal barrier. Additionally, the oxidative stress and GIT dysfunction in autistic children have both been reported to be related to mitochondrial dysfunction. What is the connection between them? Moreover, specific changes in the GIT microbiota are clearly observed in most autistic children, and the related mechanisms and the connection among ASD, the GIT microbiota, and oxidative stress are also discussed, providing a theory and molecular strategies for clinical practice as well as further studies.


2019 ◽  
Vol 20 (22) ◽  
pp. 5727 ◽  
Author(s):  
Zheng-Shun Wen ◽  
Ming Du ◽  
Zhen Tang ◽  
Tian-Yi Zhou ◽  
Zhong-Shan Zhang ◽  
...  

Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.


2020 ◽  
Author(s):  
Xuan Zhang ◽  
Yanjun Tong ◽  
Xiaomei Lyu ◽  
Jin Wang ◽  
Yuxue Wang ◽  
...  

Abstract Background: The pathogenesis of inflammatory bowel disease (IBD) might be related to the local inflammatory damage and the dysbacteriosis of intestinal flora. Probiotics can regulate the intestinal flora and ameliorate IBD. The probiotic Bacillus subtilis strain B. subtilis JNFE0126 was used as the starter of fermented milk. However, the therapeutic effects of B. subtilis fermented milk on IBD remains to be explored.Methods:The therapeutic effect of the B. subtilis fermented milk on DSS-induced IBD model mice was evaluated. The disease activity index (DAI) and the pathological features of small intestinal and colonic mucosa were examined. For exploring the action mechanism of B. subtilis, immunohistochemical staining and western-blotting were used to analyse the expression of the pro-inflammatory/anti-inflammatory cytokines, the proliferation of the intestinal stem cells, and the reconstruction of the mucosa barrier. The alteration of gut microbiota was investigated by taxonomic analysis.Results: The DAI of IBD was significantly decreased through oral administration of B. subtilis (JNFE0126) fermented milk, and the intestinal mucosa injury was attenuated. Moreover, B. subtilis could reduce the inflammatory response of the intestinal mucosa, induce proliferation of the intestinal stem cell, and promote reconstruction of the mucosal barrier. Furthermore, B. subtilis could rebalance the intestinal flora, increasing the abundance of Bacillus, Alistipes and Lactobacillus, while decreasing the abundance of Escherichia and Bacteroides.Conclusion: Oral administration of the B. subtilis fermented milk could alleviate DSS-induced IBD via inhibition of inflammatory response, promotion of the mucosal barrier reconstruction and regulation of the intestinal flora.


2019 ◽  
Author(s):  
yan liu ◽  
Jianguang Hu ◽  
Xiaoshi Zhong ◽  
Jing Yan ◽  
Daoyuan Zhou ◽  
...  

Abstract Background Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy.Methods Patients were recruited during 2017-2019 and divided into healthy control group (CT), CKD non-dialysis group (CKD), hemodialysis group (HD) and peritoneal dialysis group (PD). Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed.Results Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae , Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport.Conclusion Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.


2020 ◽  
Vol 7 (3) ◽  
pp. 938-953 ◽  
Author(s):  
Wardah Azhar ◽  
Ali Raza Khan ◽  
Noor Muhammad ◽  
Bohan Liu ◽  
Ge Song ◽  
...  

Metallic oxide nanoparticles (NPs) have received great importance due to their unique properties and valuable applications in various fields.


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