scholarly journals Gut Microbiota, Combined with Metabolomics, Reveals the Mechanism of Curcumol on Liver Fibrosis in Mice

Author(s):  
Yang Zheng ◽  
Jiahui Wang ◽  
Jiaru Wang ◽  
Ruizhu Jiang ◽  
Tianjian Liang ◽  
...  

Abstract Background:Liver fibrosis is a reversible pathological process, and its prevention and treatment are of great significance to patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and plasma metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results will help to clarify the relationship between the gut microbiota and metabolites in the process of liver fibrosis.Results:Molecular biological testing found that curcumol could significantly improve the pathological changes of liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s anti-hepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2.Conclusions:When liver fibrosis occurs, the intestinal flora and metabolic network will be altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby regulating liver inflammation.

2020 ◽  
Author(s):  
Junhan Zhao ◽  
Jing Wang ◽  
Shengwen Yang ◽  
Ran Jing ◽  
Xi Liu ◽  
...  

Abstract Background: Lung has critical pathophysiological connections to heart and lung congestion presents one of the hallmark features of heart failure (HF). This study aimed to explore the metabolic signatures and disturbances in lungs under HF condition and provide insights on the pathophysiology of the lungs under HF condition from the perspective of metabolism.Methods: In this study, we established a rapid pacing induced HF canine model and applied a comprehensive untargeted metabolomics method to comparatively assessed the metabolomics profiles in the lung tissues from HF group and sham group. Results: Distinct metabolic signatures were identified in the lungs between beagles in HF group and sham group. 81 dysregulated metabolites were identified as differential metabolites (adjusted P <0.05, FC≥2 or≤0.5) in positive ion mode and 80 dysregulated metabolites in negative ion mode, indicating a profound metabolic alteration in the lungs under HF condition. In pathway analysis, arachidonic acid metabolism and tryptophan metabolism were identified as the most significant dysregulated metabolic pathways in the lungs from HF beagles.Conclusions: In this study, we identified profound metabolic variation and dysregulated metabolic pathways, which may deepen our understanding on the pathophysiology of the lungs under HF condition from the perspective of metabolism and open new avenues in lung congestion management in HF.


2016 ◽  
Vol 23 (4) ◽  
pp. 2016410
Author(s):  
Ivanna Koshel

The main peculiarity of aspirin-intolerant polypous rhinosinusitis pathogenesis is the presence of “genetic block” of constitutive cyclooxygenase being the key enzyme of the arachidonic acid metabolism. It justifies the necessity of studying its metabolic peculiarities.The objective of the research was to determine the level of arachidonic acid as well as the state of lipid and protein peroxidation processes in patients with aspirin-intolerant polypous rhinosinusitis.Materials and methods. The levels of arachidonic acid, malondialdehyde and oxidative modification of serum proteins were studied in 20 patients with aspirin-intolerant polypous rhinosinusitis and 7 healthy individuals.Results. Significantly elevated levels of arachidonic levels were observed. The search for alternative metabolic pathways stimulated lipid and protein peroxidation processes and led to the increase in the levels of malondialdehyde and oxidative modification of serum proteins. The peculiarities of biochemical changes indicated pro-inflammatory orientation of lipid metabolism.Conclusions. The obtained data confirmed the hypothesis of “genetic block” of the arachidonic acid metabolism as the main pathogenetic component of aspirin-intolerant polypous rhinosinusitis and allowed us to clearly interpret biochemical picture of the disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxia Zhu ◽  
Yilin Wu ◽  
Hui Liu ◽  
Caini Jiang ◽  
Lili Huo

The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children’s intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Wenyi Zhou ◽  
Yiyu Cheng ◽  
Ping Zhu ◽  
M. I. Nasser ◽  
Xueyan Zhang ◽  
...  

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hongxing Wang ◽  
Nanyang Zhang ◽  
Kehua Fang ◽  
Xiaotian Chang

Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly alleviated CIA. Metabolomics and transcriptomics, as well as their integrative analysis, detected significant changes in the pathways of bile secretion, cholesterol and linoleic acid metabolism in the plasma, liver and spleen during the CIA process and the opposite changes following 2-DG treatment, whereas the expression of the genes regulating these metabolic pathways were changed only in the spleen. In the rat liver, levels of (S)-5-diphosphomevalonic acid in the terpenoid backbone biosynthesis pathway were significantly decreased during CIA progression and increased following 2-DG treatment, and levels of taurochenodeoxycholic acid in the pentose and glucuronate interconversions pathway showed the opposite results. In the spleen, levels of 3-methoxy-4-hydroxyphenylglycol glucuronide in bile secretion and 12(S)-leukotriene B4 in arachidonic acid metabolism were significantly decreased during CIA progression and increased following 2-DG treatment. The changes in the gene-metabolite network of bile secretion in the spleen correlated with a decreased plasma L-acetylcarnitine level in CIA rats and an increase following 2-DG treatment. Our analysis suggests the involvement of spleen and liver metabolism in CIA under the control of glycolysis.


2020 ◽  
Author(s):  
Jiabao Liao ◽  
Xuehua Xie ◽  
Jinmei Gao ◽  
Zhaiyi Zhang ◽  
Fei Qv ◽  
...  

Abstract BackgroundJian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. MethodsIn this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 8 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16s rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6 and TNF-α in serum and liver.ResultsJGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells into the liver. 16s rRNA analysis exhibited that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes to Bacteroidetes ratio and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment, and inflammation analysis showed decreased levels of IL-1β, IL-6, and TNF-α in the serum and liver after treatment. ConclusionsOur study illustrates that JGXZ ameliorates NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating liver inflammation.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248351
Author(s):  
Lyrialle W. Han ◽  
Yuanyuan Shi ◽  
Alison Paquette ◽  
Lu Wang ◽  
Theo K. Bammler ◽  
...  

Pregnancy is associated with metabolic changes to accommodate the mother and her growing fetus. The microbiome has been shown to modulate host metabolism of endogenous and exogenous substances. However, the combined effects of pregnancy and the microbiome on host metabolism have not been investigated. The objective of this study was to investigate how the microbiome affects overall hepatic metabolic processes during pregnancy. We assessed these changes within 4 groups of C57BL/6 mice: conventional non-pregnant, conventional pregnant, germ-free non-pregnant, and germ-free pregnant mice. We performed RNA-seq analysis on liver tissues and LC-MS/MS analysis of the plasma to assess the effects of pregnancy and the microbiome on hepatic transcriptome and untargeted plasma metabolome to describe metabolic changes as results of both pregnancy and lack of microbiome. By integrating transcriptomics and metabolomics data, we identified eight metabolic pathways that were significantly enriched for differentially expressed genes associated with pregnancy in both conventional and germ-free mice. Notably, of the eight pathways, 4 pathways (retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism, and steroid hormone biosynthesis) which are all critical for normal pregnancy and fetal development were affected by the germ-free status in pregnant mice, but not at all in non-pregnant mice, indicating that the alterations in these four pathways caused by the lack of microbiome are unique for pregnancy. These results provide novel insight into the role of the microbiome in modulating host metabolic processes critical for maternal health and fetal development during pregnancy.


2020 ◽  
Author(s):  
Yuping Yang ◽  
Shaoqiu Chen ◽  
Yumin Liu ◽  
Yuanlong Hou ◽  
Xie Xie ◽  
...  

AbstractCalorie restriction (CR) can improve the metabolic balance of adults and elevate the relative abundance of probiotic bacteria in the gut while promoting longevity. However, the interaction between remodeled intestinal flora and metabolic improvement, as well as the mechanism for probiotic bacterial increase, are still unclear. In this study, using a metabolomics platform, we demonstrate for the first time, that CR leads to increased levels of malate and its related metabolites in biological samples. Next, we investigated the effects of CR on the gut microbial genome and the expression of mRNA related to energy metabolism which revealed a partially elevated TCA cycle and a subsequently promoted glyoxylate cycle, from which large amounts of malate can be produced to further impact malate related pathways in the host liver. Through the identification of key “hungry” metabolites produced by the gut microbiota that function in the promotion of autophagy in the host, further insight has been gained about a functional metabolic network important for both host-microbial symbiosis and maintenance of host health.


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