Untargeted Metabolomic Screen Reveals Changes in Human Plasma Metabolite Profiles Following Consumption of Fresh Broccoli Sprouts

Housley, Lauren; Magaña, Armando Alcázar; Hsu, Anna; Beaver, Laura M.; Wong, Carmen P.; Stevens, Jan F.; Choi, Jaewoo; Jiang, Yuan; Bella, Deborah; Williams, David E.; Maier, Christoph; Shannon, Jackilen; Dashwood, Roderick H.; Ho, Emily

doi:10.1002/mnfr.201700665

Cited by 30 publications

(21 citation statements)

References 28 publications

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“…Previously, a small clinical study reported changes in plasma fatty acids and GSH/GSH component levels after even a single meal of broccoli sprouts, similar to pathways we report here for rat plasma [29]. Differences in findings might be due to the shorter duration of the clinical study.…”

Section: Discussionsupporting

confidence: 82%

Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

et al. 2020

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Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC–MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut–liver axis health.

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Section: Discussionsupporting

confidence: 82%

Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

et al. 2020

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“…This software allows for the correction of metabolite intensity with the intensity of the internal standards. Data obtained with MultiQuant was imported into MarkerView software (AB SCIEX) for initial data visualization [52]. Student’s t-tests were performed with GraphPad Prism Software (GraphPad, La Jolla, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Raw data from un-targeted lipidomic analysis was imported into Progenesis QI software (Version 2.3, Nonlinear Dynamics, Waters) in order to perform data normalization, feature detection, peak alignment, and peak integration [52]. A repeated measure analysis of variance (ANOVA) was also performed using Progenesis QI software in order to identify significantly alter features [52]. Similarly, we obtained the q -values based on the p -values in order to adjust for multiple comparisons.…”

Section: Methodsmentioning

confidence: 99%

Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female Ldlr -/- mice

et al. 2019

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Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease worldwide, particularly in obese and type 2 diabetic individuals. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis ( NASH ); and NASH can progress to cirrhosis, primary hepatocellular carcinoma ( HCC ) and liver failure. As such, NAFLD has emerged as a major public health concern. Herein, we used a lipidomic and transcriptomic approach to identify lipid markers associated with western diet ( WD ) induced NASH in female mice. Methods Female mice (low-density lipoprotein receptor null ( Ldlr -/- ) were fed a reference or WD diet for 38 and 46 weeks. Transcriptomic and lipidomic approaches, coupled with statistical analyses, were used to identify associations between major NASH markers and transcriptomic & lipidomic markers. Results The WD induced all major hallmarks of NASH in female Ldlr -/- mice, including steatosis (SFA, MUFA, MUFA-containing di- and triacylglycerols), inflammation ( TNFα) , oxidative stress (Ncf2) , and fibrosis (Col1A) . The WD also increased transcripts associated with membrane remodeling (LpCat) , apoptosis & autophagy ( Casp1 , CtsS ), hedgehog ( Taz ) & notch signaling ( Hey1 ), epithelial-mesenchymal transition (S1004A) and cancer ( Gpc3 ). WD feeding, however, suppressed the expression of the hedgehog inhibitory protein ( Hhip ), and enzymes involved in triglyceride catabolism ( Tgh/Ces3 , Ces1g) , as well as the hepatic abundance of C 18-22 PUFA-containing phosphoglycerolipids (GpCho, GpEtn, GpSer, GpIns). WD feeding also increased hepatic cyclooxygenase (Cox1 & 2) expression and pro-inflammatory ω6 PUFA-derived oxylipins (PGE2), as well as lipid markers of oxidative stress (8-iso-PGF2α). The WD suppressed the hepatic abundance of reparative oxylipins (19, 20-DiHDPA) as well as the expression of enzymes involved in fatty epoxide metabolism ( Cyp2C , Ephx ). Conclusion WD-induced NASH in female Ldlr -/ - mice was characterized by a massive increase in hepatic neutral and membrane lipids containing SFA and MUFA and a loss of C 18-22 PUFA-containing membrane lipids. Moreover, the WD increased hepatic pro-inflammatory oxylipins and suppressed the hepatic abundance of reparative o...

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“…Fascinatingly, underlying mechanisms and key molecular targets involved in the ability of cruciferous vegetables to improve human health have been characterized through plasma metabolite profiles before and after human consumption of broccoli sprouts. The investigation identified several potential molecular targets of crucifers, including fatty acids, glutathione, glutamine, cysteine, dehydroepiandrosterone, and deoxyuridine monophosphate, aiding in the study of established and emerging health benefits that the consumption of cruciferous vegetables may possess . It is apparent that future research utilizing metabolomics and its integration with additional –omics technologies has strong potential of helping both the fields of bladder cancer and isothiocyanates significantly advance.…”

Section: Future Approachesmentioning

confidence: 99%

Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention

Abbaoui

Lucas

Riedl

et al. 2018

Molecular Nutrition Food Res

126

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Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.

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Untargeted Metabolomic Screen Reveals Changes in Human Plasma Metabolite Profiles Following Consumption of Fresh Broccoli Sprouts

Abstract: This investigation identifies several potential molecular targets of crucifers that may aid in studying established and emerging health benefits of consuming cruciferous vegetables and related bioactive compounds.

Cited by 30 publications

References 28 publications

Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female Ldlr -/- mice

Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention

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