scholarly journals Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration

2021 ◽  
Author(s):  
Haicui Wu ◽  
Theo Y. C. Lam ◽  
Tim-Fat Shum ◽  
Tsung-Yu Tsai ◽  
Jiachi Chiou
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Acetate Salt ◽  
Factor Α ◽  
Captopril Treatment ◽  
Gut Microbiota Dysbiosis ◽  
Necrosis Factor

AbstractThe role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.

scholarly journals Human Gut Microbiota in Health and Selected Cancers

2021 ◽  
Vol 22 (24) ◽  
pp. 13440
Author(s):  
Aleksandra Sędzikowska ◽  
Leszek Szablewski
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Human Gut ◽  
Vast Number ◽  
Human Gut Microbiota ◽  
Internal And External Factors ◽  
Number Of Bacteria ◽  
Gut Microbiota Dysbiosis

The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto’s thyroidis and Graves’ disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.

scholarly journals Food Preservatives Induce Proteobacteria Dysbiosis in Human-Microbiota Associated Nod2-Deficient Mice

2019 ◽  
Vol 7 (10) ◽  
pp. 383 ◽  
Author(s):  
Hrncirova ◽  
Machova ◽  
Trckova ◽  
Krejsek ◽  
Hrncir
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Food Additives ◽  
Wild Type ◽  
Food Preservatives ◽  
Human Microbiota ◽  
Immune Mediated ◽  
Exposure Levels ◽  
Gut Microbiota Dysbiosis

: The worldwide incidence of many immune-mediated and metabolic diseases, initially affecting only the wealthy Western countries, is increasing rapidly. Many of these diseases are associated with the compositional and functional alterations of gut microbiota, i.e., dysbiosis. The most consistent markers of the dysbiosis are a decrease in microbiota diversity and an expansion of Proteobacteria. The role of food preservatives as potential triggers of gut microbiota dysbiosis has been long overlooked. Using a human microbiota-associated mouse model, we demonstrate that a mixture of common antimicrobial food additives induces dysbiosis characterised by an overgrowth of Proteobacteria phylum and a decrease in the Clostridiales order. Remarkably, human gut microbiota in a Nod2-deficient genetic background is even more susceptible to the induction of Proteobacteria dysbiosis by additives than the microbiota in a wild-type background. To conclude, our data demonstrate that antimicrobial food additives trigger gut microbiota dysbiosis in both wild-type and Nod2-deficient backgrounds and at the exposure levels reached in European populations. Whether this additive-modified gut microbiota plays a significant role in the pathogenesis of immune-mediated and metabolic diseases remains to be elucidated.

Combination of IL-17 and TNFα induces a pro-inflammatory, pro-coagulant and pro-thrombotic phenotype in human endothelial cells

2012 ◽  
Vol 71 (5) ◽  
pp. 768-776 ◽  
Author(s):  
Arnaud Hot ◽  
Vanina Lenief ◽  
Pierre Miossec
Keyword(s):  
Platelet Aggregation ◽  
Migration And Invasion ◽  
Human Endothelial Cells ◽  
Qrt Pcr ◽  
Functional Assays ◽  
Affymetrix Microarrays ◽  
Stromal Cell Derived Factor ◽  
Factor Α ◽  
Necrosis Factor

ObjectiveCardiovascular events remain the leading cause of death in rheumatoid arthritis (RA). To study the role of cytokines in these observations, the effects of tumour necrosis factor α (TNFα) and interleukin (IL)-17, a classical and a new key player in RA, were assessed in endothelial cell (EC) dysfunction.MethodsPrimary human EC were treated with IL-17 alone or combined with TNFα. mRNA expression was quantified by qRT PCR and Affymetrix microarrays. The role of IL-17 was studied using functional assays of platelet aggregation, EC migration and invasion.ResultsIL-17 alone induced 248 pro-inflammatory genes and 9803, when combined with TNFα. IL-17 plus TNFα induced synergistically chemokine genes such as CCL5, IL-8 and cytokine genes such as IL-6. In contrast, IL-17 decreased genes involved in the regulation of inflammation such as IL-33. IL-17 induced EC migration and invasion in synergy with TNFα. Such invasion was inhibited with an antiCXCR4 antibody, indicating the contribution of the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 axis. Supernatants of IL-17-treated EC induced strong platelet aggregation. IL-17 inhibited endothelial CD39/ATPDase expression, an inhibitor of platelet activation. Finally, IL-17 enhanced genes critical for coagulation such as tissue factor and decreased thrombomodulin, leading to a pro-thrombotic state.ConclusionThese results indicate that IL-17 specifically when combined with TNFα has major pro-coagulant and pro-thrombotic effects on vessels.

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