Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach

Vitale, Marilena; Hanhineva, Kati; Koistinen, Ville; Auriola, Seppo; Paananen, Jussi; Costabile, Giuseppina; Pepa, Giuseppe Della; Rivellese, Angela Albarosa; Riccardi, Gabriele; Giacco, Rosalba

doi:10.1016/j.numecd.2020.12.022

Cited by 9 publications

(10 citation statements)

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“…Est: estimate (rho) of the (partial) Spearman correlation or the linear models; p was corrected for multiple comparisons with false discovery rate (FDR). FDR < 0.005 for correlation analyses and FDR < 0.05 for linear models in DC and FDR < 0.05 for both models in RC were considered significant, printed in bold a ESI electrospray ionization, positive or negative mode, HILIC hydrophilic interaction chromatography, m/z mass-to-charge ratio, RP reversed-phase, RT retention time b Some metabolites could be categorized as alkylresorcinols (A) [ 12 , 49 ], betaines (B) [ 52 ], microbial metabolites (M), or other metabolites previously [ 12 , 13 ] associated with wholegrains (O) c Level of identification refers to the reporting guidelines by Metabolomics Standard Initiatives [ 41 ]. Only level I (metabolites with matching m/z , RT, and MS2 spectra with reference compounds ran with the same procedure) and II (matching m/z and MS2 spectra as publicly available spectral libraries) were reported in this table.…”

Section: Resultsmentioning

confidence: 99%

“…Besides annotating metabolites from the discovery and replication strategies described above, we further annotated metabolites previously associated with WG intake [ 10 , 12 , 13 , 49 , 52 , 53 ] from the data. This list of metabolites included ARs, betaines, and other metabolites (Supplementary Table 4).…”

Section: Methodsmentioning

confidence: 99%

“…More recently, trimethylamine-N-oxide and various betainized compounds have been reported from consuming a WG-rich diet [ 10 , 11 ]. In addition, lower levels of several endogenous compounds, such as serotonin, taurine, and glycerophosphocholine, and phosphatidylcholines (PCs) have also been reported after WG intake [ 12 , 13 ]. However, the metabolism of these compounds in the body seems to depend on individual factors, such as age, sex, and BMI [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study

et al. 2022

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Purpose To identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders. Methods We selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200). Results Direct associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort. Conclusions The identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study

et al. 2022

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“…Whole grains have previously been reported to affect plasma levels of several GPLs. Compared to refined grains, whole grain intervention has been found to reduce plasma levels of the choline derivative glycerophosphocholine (GPC) ( 18 ), and increase plasma levels of various lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) species ( 19 , 20 ). To our knowledge, no prior studies have reported the effects of whole grain intervention on the specific plasma GPL that we measured.…”

Section: Discussionmentioning

confidence: 99%

Effects of a 12-week whole-grain or refined wheat intervention on plasma acylcarnitines, bile acids and signaling lipids, and association with liver fat: A post-hoc metabolomics study of a randomized controlled trial

Gijbels

Schutte²,

Esser³

et al. 2022

Front. Nutr.

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BackgroundWe previously showed that whole-grain wheat (WGW) consumption had beneficial effects on liver fat accumulation, as compared to refined wheat (RW). The mechanisms underlying these effects remain unclear.ObjectiveIn this study, we investigated the effects of WGW vs. RW consumption on plasma metabolite levels to explore potential underlying mechanisms of the preventive effect of WGW consumption on liver fat accumulation.MethodsTargeted metabolomics of plasma obtained from a concluded 12-week double-blind, randomized controlled trial was performed. Fifty overweight or obese men and women aged 45–70 years with mildly elevated levels of plasma cholesterol were randomized to either 98 g/d of WGW or RW products. Before and after the intervention, a total of 89 fasting plasma metabolite concentrations including acylcarnitines, trimethylamine-N-oxide (TMAO), choline, betaine, bile acids, and signaling lipids were quantified by UPLC-MS/MS. Intrahepatic triglycerides (IHTG) were quantified by 1H-MRS, and multiple liver markers, including circulating levels of β-hydroxybutyrate, alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (γ-GT), serum amyloid A (SAA), and C-reactive protein, were assessed.ResultsThe WGW intervention increased plasma concentrations of four out of 52 signaling lipids—lysophosphatidic acid C18:2, lysophosphatidylethanolamine C18:1 and C18:2, and platelet-activating factor C18:2—and decreased concentrations of the signaling lipid lysophosphatidylglycerol C20:3 as compared to RW intervention, although these results were no longer statistically significant after false discovery rate (FDR) correction. Plasma concentrations of the other metabolites that we quantified were not affected by WGW or RW intervention. Changes in the above-mentioned metabolites were not correlated to change in IHTG upon the intervention.ConclusionPlasma acylcarnitines, bile acids, and signaling lipids were not robustly affected by the WGW or RW interventions, which makes them less likely candidates to be directly involved in the mechanisms that underlie the protective effect of WGW consumption or detrimental effect of RW consumption on liver fat accumulation.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT02385149].

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“…Anthocyanins are pigments of colored cereals: wheat, rye, millet, barley, rice, maize, and sorghum ( 6 ). Several studies, both in vitro and in vivo , demonstrated that anthocyanins have positive health effects ( 6 , 74 ): antioxidant activity ( 75 , 76 ), inhibition of cholesterol absorption ( 77 , 78 ), reduction of starch digestibility ( 79 ), neuro-protection ( 80 ), anticancer ( 81 ) and antimetastatic activity ( 82 ), anti-hypertension effect ( 83 ), retinal protection ( 84 ), body fat reduction ( 85 ), hepatoprotection ( 86 ), prevention of metabolic syndrome ( 31 , 87 ), enhancement of the immune response ( 82 ), anti-aging effect ( 88 ).…”

Section: Relevant Phytochemicals In Cereals and Their Effect On Healthmentioning

confidence: 99%

The Impact of Cereal Grain Composition on the Health and Disease Outcomes

et al. 2022

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Whole grains are a pivotal food category for the human diet and represent an invaluable source of carbohydrates, proteins, fibers, phytocompunds, minerals, and vitamins. Many studies have shown that the consumption of whole grains is linked to a reduced risk of cancer, cardiovascular diseases, and type 2 diabetes and other chronic diseases. However, several of their positive health effects seem to disappear when grains are consumed in the refined form. Herein we review the available literature on whole grains with a focus on molecular composition and health benefits on many chronic diseases with the aim to offer an updated and pragmatic reference for physicians and nutrition professionals.

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Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach

Cited by 9 publications

References 29 publications

Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study

Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study

Effects of a 12-week whole-grain or refined wheat intervention on plasma acylcarnitines, bile acids and signaling lipids, and association with liver fat: A post-hoc metabolomics study of a randomized controlled trial

The Impact of Cereal Grain Composition on the Health and Disease Outcomes

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