scholarly journals Chlorothalonil induces metabolic syndrome in mice by regulating host gut microbiota and bile acids metabolism via FXR pathways

2021 ◽  
Author(s):  
Zhiyuan Meng ◽  
Sen Yan ◽  
Wei Sun ◽  
Jin Yan ◽  
Miaomiao Teng ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Low Dose ◽  
Daily Intake ◽  
Dependent Manner ◽  
Glycolipid Metabolism ◽  
Pesticides Exposure ◽  
Bile Acids Metabolism

Abstract Background：The most commonly used organochlorine pesticide, chlorothalonil (CHI), is ubiquitous in a natural environment and poses many adverse effects to organisms. Unfortunately, the toxicity mechanisms of CHI have not been clarified yet.Results: This study found that the low-dose CHI based on acceptable daily intake (ADI) level could induce metabolic syndrome (MetS) in mice, including obesity, hepatic steatosis, dyslipidemia, and insulin resistance. In addition, exposure to low-dose CHI could induce an imbalance in the gut microbiota of mice, resulting in a significant increase in the ratio of Firmicutes to Bacteroidetes. Furthermore, the results of the antibiotic treatment and gut microbiota transplantation experiments showed that the low-dose CHI could induce MetS in mice in a gut microbiota-dependent manner. Based on the results of targeted metabolomics and gene expression analysis, the low-dose CHI could disturb the serum metabolism of bile acids (BAs) in mice, causing the inhibition of the signal response of BAs receptor farnesol X receptor (FXR) and leading to glycolipid metabolism disorders in liver tissue and epididymal white adipose tissue (epiWAT) of mice. The administration of FXR agonist GW4064 and CDCA could significantly improve the low-dose CHI-induced MetS in mice.Conclusions: In conclusion, the low-dose CHI was found to induce MetS in mice by regulating the gut microbiota and BAs metabolism via the FXR signaling pathway. This study provides evidence linking the gut microbiota and pesticides exposure with the progression of MetS, demonstrating the key role of gut microbiota in the toxic effects of pesticides.

scholarly journals IgA dysfunction induced by the early-lifetime disruption of gut microbiota aggravates diet–induced metabolic syndrome in mice

2021 ◽  
Author(s):  
Jielong Guo ◽  
Xue Han ◽  
Yilin You ◽  
Weidong Huang ◽  
Zhan Jicheng
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Early Life ◽  
Low Dose ◽  
Dependent Manner ◽  
Wild Type ◽  
Bacterial Composition ◽  
Germ Free ◽  
Iga Response ◽  
Intestinal Iga

Abstract BackgroundLow-dose antibiotic contamination in animal food is still a severe food safety problem worldwide. Penicillin is one of the main classes of antibiotics being detected in food. Previous studies have shown that transient exposure of low-dose penicillin (LDP) during early life resulted in metabolic syndrome (MetS) in mice. However, the underlying mechanism(s) and efficient approaches to counteracting this are largely unknown.MethodsWild-type (WT) or secretory IgA (SIgA)-deficient (Pigr-/-) C57BL/6 mice were exposed to LDP or not from several days before birth to 30 d of age. Five times of FMT or probiotics (a mixture of Lactobacillus bulgaricus and L. rhamnosus GG) treatments were applied to parts of these LDP-treated mice from 12 d to 28 d of life. Bacterial composition from different regions (mucosa and lumen) of the colon and ileum were analyzed through 16S rDNA sequencing. Intestinal IgA response was analyzed. Multiple parameters related to MetS were also determined. In addition, germ-free animals and in vitro tissue culture were also used to determine the correlations between LDP, gut microbiota (GM) and intestinal IgA response.ResultsLDP disturbed the intestinal bacterial composition, especially for ileal mucosa, the main inductive and effective sites of IgA response, in 30-d-old mice. The alteration of early GM resulted in a persistent inhibition of the intestinal IgA response, leading to a constant reduction of fecal and caecal SIgA levels throughout the 25-week experiment, which is early life-dependent, as transfer of LDP-GM to 30 d germ-free mice only resulted in a transient reduction in fecal SIgA. LDP-induced reduction in SIgA led to a decrease in IgA+ bacteria and a dysbiosis in the ileal mucosal samples of 25 week wild-type but not Pigr-/- mice. Moreover, LDP also resulted in increases in ileal bacterial encroachment and adipose inflammation, along with an enhancement of diet-induced MetS in an intestinal SIgA-dependent manner. Furthermore, several times of FMT or probiotic treatments during LDP treatment are efficient to fully (for FMT) or partially (for probiotics) counteract the LDP-effect on both GM and metabolism.ConclusionsEarly-life LDP-induced enhancement of diet-induced MetS is mediated by intestinal SIgA, which could be (partially) restored by FMT or probiotics treatment.

scholarly journals Role of Gut Microbiota in the Pathogenesis of Cardiovascular Diseases and Metabolic Syndrome

2018 ◽  
Vol 14 (4) ◽  
pp. 567-574 ◽  
Author(s):  
O. M. Drapkina ◽  
O. E. Shirobokikh
Keyword(s):  
Heart Failure ◽  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Cardiovascular Diseases ◽  
Gut Microbiota ◽  
Bile Acids ◽  
G Protein ◽  
Short Chain Fatty Acids ◽  
Short Chain

The role of gut microbiota in the pathogenesis of cardiovascular diseases (CVD) and metabolic syndrome has attracted massive attention in the past decade. Accumulating evidence has revealed that the metabolic potential of gut microbiota can be identified as a contributing factor in the development of atherosclerosis, hypertension, heart failure, obesity, diabetes mellitus. The gut-host interaction occurs through many pathways including trimethylamine-N-oxide pathway (TMAO), short-chain fatty acids and second bile acids pathways. TMAO (the hepatic oxidation product of the microbial metabolite of trimethylamine) enhances platelet hyperreactivity and thrombosis risk and predicts major adverse cardiovascular events. Short-chain fatty acids and second bile acids, which are produced with the help of microbiota, can modulate host lipid metabolism as well as carbohydrate metabolism through several receptors such as G-protein-coupled receptors 41,43, farnesoid X-receptor, Takeda-G-protein-receptor-5. This way microbiota can impact host lipid levels, processes of weight gain, insulin sensitivity. Besides these metabolism-dependent pathways, there are some other pathways, which link microbiota and the pathogenesis of CVD. For example, lipopolysaccharide, the major component of the outer bacterial membrane, causes metabolic endotoxemia and low-grade systemic inflammation and contribute this way to obesity and progression of heart failure and atherosclerosis. This review aims to illustrate the complex interplay between microbiota, their metabolites, and the development and progression of CVD and metabolic syndrome. It is also discussed how modulating of gut microbiota composition and function through diet, prebiotics, probiotics and fecal microbiota transplantation can become a novel therapeutic and preventative target for CVD and metabolic syndrome. Many questions remain unresolved in this field and undoubtedly further studies are needed.

scholarly journals Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition

2021 ◽  
Author(s):  
Rou-An Chen ◽  
Wei-Kai Wu ◽  
Suraphan Panyod ◽  
Po-Yu Liu ◽  
Hsiao-Li Chuang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bile Acids ◽  
Early Life ◽  
Low Dose ◽  
Fecal Microbiota Transplantation ◽  
Daily Intake ◽  
Growth Promoter ◽  
Antibiotic Residues ◽  
Metabolic Complications ◽  
Host Metabolism

Abstract Low dose antibiotic residues in food potentially contribute to obesity and metabolic dysfunction. However, the effect of chronic exposure to very low-dose antibiotic residue (~1000-fold lower than the therapeutic dose) on gut microbiota and host metabolism is poorly understood. Herein the effect of exposure to a residual dose of tylosin—an antibiotic growth promoter—on host metabolism and gut microbiota is explored in a mouse model. Theoretical maximal daily intake (TMDI) dose of tylosin facilitates high-fat diet-induced obesity, induces insulin resistance, and perturbs gut microbiota composition. Moreover, obesity-related phenotypes are transferrable to germ-free recipient mice following fecal microbiota transplantation. Tylosin TMDI exposure restricted to early life is sufficient to induce metabolic complications, alter the abundance of specific bacteria related to host metabolic homeostasis later in life, and modify the composition of short-chain fatty acids and bile acids. Finally, tylosin TMDI exposure induces lasting metabolic consequences via elevating the ratio of primary to secondary bile acids and its downstream FGF15 signaling pathway. Hence, exposure to very low doses of antibiotic residues, whether continuously or in early life, can exert long-lasting effects on host metabolism by altering gut microbiota and their metabolites.

scholarly journals Systemic, but not local, low-grade endotoxinemia increases plasma sCD163 independently of the cortisol response

2019 ◽  
Vol 8 (2) ◽  
pp. 95-99
Author(s):  
Ermina Bach ◽  
Niels Møller ◽  
Jens Otto L Jørgensen ◽  
Mads Buhl ◽  
Holger Jon Møller
Keyword(s):  
Metabolic Syndrome ◽  
Low Dose ◽  
Human Subjects ◽  
Femoral Vein ◽  
Independent Effect ◽  
Low Grade ◽  
Similar Response ◽  
Dependent Manner ◽  
The Metabolic Syndrome ◽  
And Gender

Aims/hypothesis The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner. Methods We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively. Results: Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163. Conclusion: Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

scholarly journals Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

scholarly journals Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: a randomized crossover trial

2020 ◽  
Vol 111 (4) ◽  
pp. 864-876
Author(s):  
Anne K Eriksen ◽  
Carl Brunius ◽  
Mohsen Mazidi ◽  
Per M Hellström ◽  
Ulf Risérus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Ldl Cholesterol ◽  
Oral Glucose ◽  
Microbiota Composition ◽  
Whole Grain ◽  
The Metabolic Syndrome

ABSTRACT Background A whole-grain (WG)–rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. Objectives The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. Methods Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4–8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. Results The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (−0.06 and −0.09 mmol/L, respectively; P &lt; 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P &lt; 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. Conclusions WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.

Potential Synergism of Green Tea and Aspirin as a Possible Cause of Bleeding in a Diabetic

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4504-4504
Author(s):  
Roger C Munro ◽  
Lisa J Wakeman ◽  
Saad Al-Ismail
Keyword(s):  
Metabolic Syndrome ◽  
Platelet Aggregation ◽  
Green Tea ◽  
Causal Effect ◽  
Daily Intake ◽  
Water Extract ◽  
Serum Triglyceride ◽  
Hot Water ◽  
Diabetic Patients ◽  
Dependent Manner

Abstract A 58 year old lady with Metabolic Syndrome of 10 years duration presented with post-menopausal PV bleeding, haematuria, occasional epistaxis and ecchymoses. Prescribed medication which had remained unchanged for the preceding two years included daily doses (mgms) of Aspirin (150), Atenelol (50), Metformin (500 × 3), Bendroflumethiazide (2.5), Losartan (50) and Simvastatin (20). Intravenous urogram, cystoscopy, cytological examination of urine sediment, hysteroscopy, a cervical scan and endometrial biopsies showed neither evidence of overt pathology nor any physiological indication for the cause of haematuria or PV bleeding. Tests for urinary infection were negative. Apart from the raised blood glucose (9.1: NR 3.3 – 6.0 mmol/L), the biochemistry profile including liver enzymes, coagulation profile and blood count were normal (Platelets = 265 × 109/L). Bleeding episodes were observed after commencement of a daily intake of 7–8 cups of green tea for a period of six months. Green tea intake was self-instigated in response to reported amelioration of risk factors associated with Metabolic Syndrome (reduction in LDL cholesterol and serum triglyceride levels; elevation of protective HDL; potent antioxidant activity; ACE inhibition and promotion of glucose metabolism). Hot water extract of green tea specifically inhibits platelet adhesion and lowers sub-maximal platelet aggregation and prolongs the lag time in a dose-dependent manner. Previous fractionation studies of these hot water extracts, has revealed that the tea catechins (tannins) actively inhibit thromboxane A2 production and that ester-type catechins are more effective than free-type catechins. One of the ester-type catechins, epigallocatechin gallate (EGCG), suppresses thrombin and collagen-induced platelet aggregation completely at a concentration of 0.2 mg/ml. EGCG also inhibits aggregation by a mechanism which differs from that of aspirin by inhibiting platelet activating factor (PAF). The IC50 values of EGCG and aspirin indicate that their potencies are comparable. Bleeding symptoms ceased two weeks after the patient stopped drinking green tea. Our assumption of the causal effect of green tea on anomalous bleeding in this patient needs to be confirmed by structured platelet function tests in both aspirinised and non-aspirinised patients. Since inhibition of cyclo-oxygenase is an additional anti-thrombotic property of aspirin which differs from that of green tea, diabetic patients taking prophylactic low-dose aspirin should continue to do so and potentially beneficial ingestion of green tea should not be considered without consultation with an appropriate health professional in view of its synergistic potential on the effect of aspirin and the associated haemorrhagic risks.

Sign in / Sign up

Export Citation Format

Share Document