Search Results (35)

The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005–2010, n = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0–13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies. Full article

Type 2 diabetes (T2D) is a growing health concern with an estimated 462 million people having been diagnosed worldwide. T2D is characterized by chronically elevated blood glucose and insulin resistance, which culminate in a diminished function of the β-cell mass in its later stages. This can be perpetuated by and result in inflammation, excess reactive oxygen species production, obesity, and the dysregulation of multiple cellular pathways. Many naturally occurring small molecules have been investigated in terms of their roles in modulating glucose homeostasis and β-cell function. Many of these compounds can be found in commonly used sources of food and drink. Interestingly, a correlation has been observed between coffee consumption and T2D incidence. However, the specific compounds responsible for this correlation and their mechanisms are still somewhat undetermined. This paper reviews recent research findings on the effects of several polyphenols that are either found in coffee or are metabolites of compounds found in coffee (enterodiol, enterolactone, matairesinol, secoisolariciresinol, kaempferol, quercetin, and chlorogenic acid) on glucose homeostasis and health complications associated with glucose dysregulation, with a special emphasis on their potential anti-diabetic effects. The factors that affect polyphenol content in coffee are also addressed. Full article

This study examined the protective effect of flaxseed lignans on liver damage caused by an overdose of paracetamol (PAM). The findings demonstrated that administering 800 mg/kg/d flaxseed lignan prior to PAM significantly decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBi) levels, while it increased liver superoxide dismutase (SOD) and glutathione (GSH) levels in mice. Flaxseed lignan renovated the gut microbiota dysbiosis induced by PAM by promoting the proliferation of sulfonolipid (SL) producing bacteria such as Alistipes and lignan-deglycosolating bacteria such as Ruminococcus while inhibiting the growth of opportunistic pathogen bacteria such as Acinetobacter and Clostridium. Furthermore, flaxseed lignan modulated the serum metabolomic profile after PAM administration, specifically in the taurine and hypotaurine metabolism, phenylalanine metabolism, and pyrimidine metabolism. The study identified eight potential biomarkers, including enterolactone, cervonyl carnitine, acutilobin, and PC (20:3(5Z, 8Z, 11Z)/20:0). Overall, the results suggest that flaxseed lignan can alleviate PAM-induced hepatotoxicity and may be beneficial in preventing drug-induced microbiome and metabolomic disorders. Full article

The history of the use of natural compounds as therapeutic agents goes back many centuries. Being the first objects of interest in the early days of medicine, natural compounds are still of great relevance, considering the improvement of methods for isolation, chemical transformation, and synthesis. They are also used in oncology, with the advantage of preventing the development of toxicity to normal cells and resistance in tumor cells. One of the promising classes of natural compounds with antitumor activity is lignans. We studied a number of lignans (arctiin, honokiol, matairesinol, pinoresinol, myrislignan, enterodiol, and enterolactone) in the breast cancer cell line MCF7 and the subline MCF7/FUL with acquired resistance to the antiestrogen fulvestrant. Antiproliferative activity was assessed using the MTT test. An analysis of the level of intracellular proteins was carried out via immunoblotting. Based on the results of the screening, the most active compound was honokiol; it had the lowest IC₅₀ value for both MCF7 and MCF7/FUL cells, 19.7 μM and 9.1 μM, respectively. The revealed antiproliferative activity of honokiol against resistant cells prompted us to study its effects on intracellular proteins associated with proliferation and cell death. Honokiol suppressed the expression of Bcl-2 (an inhibitor of apoptosis) and cyclin D1 (a cell cycle regulator) in both cell lines, but this effect was more pronounced in the resistant subline. The decrease in the expression of antiapoptotic and proliferative proteins induced by honokiol is consistent with its antiproliferative effect, which is more pronounced in resistant subline MCF7/FUL. Full article

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control. Full article

The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectional data from 4685 US adults (age 43.6 ± 16.5 years; 50.4% female) participating in the National Health and Nutrition Examination Survey for 1999–2010. Dietary data were collected from one to two separate 24-hour dietary recalls and diet quality was characterized using the 2015 Healthy Eating Index. Cardiometabolic health markers included blood lipid profile, glycemic control, adiposity, and blood pressure. Microbial lignan metabolites considered were urinary concentrations of enterolignans, including enterolactone and enterodiol, with higher levels indicating a healthier gut microbial environment. Models were visually examined using a multidimensional approach and statistically analyzed using three-dimensional generalized additive models. There was a significant interactive association between diet quality and microbial lignan metabolites for triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, oral glucose tolerance, adiposity, systolic blood pressure, and diastolic blood pressure (all p < 0.05). Each of these cardiometabolic health markers displayed an association such that optimal cardiometabolic health was only observed in individuals with both high diet quality and elevated urinary enterolignans. When comparing effect sizes on the multidimensional response surfaces and model selection criteria, the strongest support for a potential moderating relationship of the gut microbiome was observed for fasting triglycerides and oral glucose tolerance. In this study, we revealed interactive associations of diet quality and microbial lignan metabolites with cardiometabolic health markers. These findings suggest that the overall association of diet quality on cardiometabolic health may be affected by the gut microbiome. Full article

There is an increasing interest in developing natural herb-infused functional beverages with health benefits; therefore, in this study, we aimed to evaluate the effect of strawberry, blueberry, and strawberry-blueberry blend decoction-based functional beverages on obesity-related metabolic alterations in high-fat and high-fructose diet-fed rats. The administration of the three berry-based beverages for eighteen weeks prevented the development of hypertriglyceridemia in obese rats (1.29–1.78-fold) and hepatic triglyceride accumulation (1.38–1.61-fold), preventing the development of hepatic steatosis. Furthermore, all beverages significantly down-regulated Fasn hepatic expression, whereas the strawberry beverage showed the greatest down-regulation of Acaca, involved in fatty acid de novo synthesis. Moreover, the strawberry beverage showed the most significant up-regulation of hepatic Cpt1 and Acadm (fatty acid β-oxidation). In contrast, the blueberry beverage showed the most significant down-regulation of hepatic Fatp5 and Cd36 (fatty acid intracellular transport). Nevertheless, no beneficial effect was observed on biometric measurements, adipose tissue composition, and insulin resistance. On the other hand, several urolithins and their derivatives, and other urinary polyphenol metabolites were identified after the strawberry-based beverages supplementation. In contrast, enterolactone was found significantly increase after the intake of blueberry-based beverages. These results demonstrate that functional beverages elaborated with berry fruits prevent diet-induced hypertriglyceridemia and hepatic steatosis by modulating critical genes involved in fatty acid hepatic metabolism. Full article

Phytoestrogens are dietary compounds with low estrogenic activity. The two main categories in the French diet are isoflavones from pulses and enterolignans metabolized by the gut flora from various lignans found in fruits, vegetables, grains, and beverages. Isoflavones and lignans have different effects on human physiology and can antagonize each other. Comprehensive lists of phytoestrogen sources were constructed based on measurements and literature data. The 24 h and 48 h dietary recalls were proposed to the volunteers of the ISOLED cohort (NCT03421184). Urine and plasma samples from these volunteers were assayed for genistein, daidzein, equol, and enterolactone. A dietary score was constructed considering the pharmacokinetic characteristics of these compounds. Correlation analyses were applied to fluid concentrations associated with dietary scores. Pearson correlations reached 0.921 (p < 0.001) for urine_IF, 0.900 (p < 0.001) for plasma_IF, 0.764 (p < 0.001) for urine_ENL, and 0.723 (p < 0.001) for plasma_ENL. ELISAs associated with careful intake assessments proved to be good tools for phytoestrogens’ exposure estimation. Full article

Lignans are non-flavonoid polyphenols present in a wide range of foods frequently consumed in the Western world, such as seeds, vegetables and fruits, and beverages such as coffee, tea and wine. In particular, the human gut microbiota (GM) can convert dietary lignans into biologically active compounds, especially enterolignans (i.e., enterolactone and enterodiol), which play anti-inflammatory and anti-oxidant roles, act as estrogen receptor activators and modulate gene expression and/or enzyme activity. Interestingly, recent evidence documenting those dietary interventions involving foods enriched in lignans have shown beneficial and protective effects on various human pathologies, including colorectal and breast cancer and cardiovascular diseases. However, considering that more factors (e.g., diet, food transit time and intestinal redox state) can modulate the lignans bioactivation by GM, there are usually remarkable inter-individual differences in urine, fecal and blood concentrations of enterolignans; hence, precise and validated analytical methods, especially gas/liquid chromatography coupled to mass spectrometry, are needed for their accurate quantification. Therefore, this review aims to summarize the beneficial roles of enterolignans, their interaction with GM and the new methodological approaches developed for their evaluation in different biological samples, since they could be considered future promising nutraceuticals for the prevention of human chronic disorders. Full article

Dietary plant lignans are converted inside the gut to enterolignans enterodiol (ED) and enterolactone (EL), which have several biological functions, and health benefits. In this study, we characterized the gut microbiome composition associated with enterolignan production using data from a cross-sectional study in the Japanese population. We identified enterolignan producers by measuring ED and EL levels in subject’s serum using liquid chromatography-tandem mass spectrometry. Enterolignan producers show more abundant proportion of Ruminococcaceae and Lachnospiraceae than non-enterolignan producers. In particular, subjects with EL in their serum had a highly diverse gut microbiome that was rich in Ruminococcaceae and Rikenellaceae. Moreover, we built a random forest classification model to classify subjects to either EL producers or not using three characteristic bacteria. In conclusion, our analysis revealed the composition of gut microbiome that is associated with lignan metabolism. We also confirmed that it can be used to classify the microbiome ability to metabolize lignan using machine learning approach. Full article

Flaxseeds are typically consumed either as whole flaxseed, ground flaxseed, flaxseed oil, partially defatted flaxseed meal, or as a milk alternative. They are considered a rich source of vitamins, minerals, proteins and peptides, lipids, carbohydrates, lignans, and dietary fiber, which have shown hypolipidemic, antiatherogenic, anticholesterolemic, and anti-inflammatory property activity. Here, an in vitro batch culture model was used to investigate the influence of whole milled flaxseed and partially defatted milled flaxseed press cake on the gut microbiota and the liberation of flaxseed bioactives. Microbial communities were profiled using 16S rRNA gene-based high-throughput sequencing with targeted mass spectrometry measuring lignan, cyclolinopeptide, and bile acid content and HPLC for short-chain fatty acid profiles. Flaxseed supplementation decreased gut microbiota richness with Firmicutes, Proteobacteria, and Bacteroidetes becoming the predominant phyla. Secoisolariciresinol, enterodiol, and enterolactone were rapidly produced with acetic acid, butyric acid, and propionic acid being the predominant acids after 24 h of fermentation. The flaxseed press cake and whole flaxseed were equivalent in microbiota changes and functionality. However, press cake may be superior as a functional additive in a variety of foods in terms of consumer acceptance as it would be more resistant to oxidative changes. Full article

Lignans are a group of natural polyphenols present in medicinal plants and in plants which are a part of the human diet for which more and more pharmacological activities, such as antimicrobial, anti-inflammatory, hypoglycemic, and cytoprotective, are being reported. However, it is their cytotoxic activities that are best understood and which have shed light on this group. Two anticancer drugs, etoposide, and teniposide, were derived from a potent cytotoxic agent—podophyllotoxin from the roots of Podophyllum peltatum. The evidence from clinical and observational studies suggests that human microbiota metabolites (enterolactone, enterodiol) of dietary lignans (secoisolariciresinol, pinoresinol, lariciresinol, matairesinol, syringaresinol, medioresinol, and sesamin) are associated with a reduced risk of some hormone-dependent cancers. The biological in vitro, pharmacological in vivo investigations, and clinical studies demand significant amounts of pure compounds, as well as the use of well-defined and standardized extracts. That is why proper extract preparation, optimization of lignan extraction, and identification are crucial steps in the development of lignan use in medicine. This review focuses on lignan extraction, purification, fractionation, separation, and isolation methods, as well as on chromatographic, spectrometric, and spectroscopic techniques for their qualitative and quantitative analysis. Full article

High-fiber plant foods contain lignans that are converted to bioactive enterolignans, enterolactone (ENL) and enterodiol (END) by gut bacteria. Previously, we conducted an intervention study to gain mechanistic insight into the potential chemoprotective effects of flaxseed lignan supplementation (secoisolariciresinol diglucoside; SDG) compared to a placebo in 42 men and women. Here, we expand on these analyses to further probe the impact of the microbial metabolite phenotype on host gene expression in response to lignan exposure. We defined metabolic phenotypes as high- or low-ENL excretion based on the microbial metabolism of SDG. RNA-seq was used to assess host gene expression in fecal exfoliated cells. Stratified by microbial ENL excretion, differentially expressed (DE) genes in high- and low-ENL excreter groups were compared. Linear discriminant analysis using the ENL phenotypes identified putative biomarker combinations of genes capable of discriminating the lignan treatment from the placebo. Following lignan intervention, a total of 165 DE genes in high-ENL excreters and 1450 DE genes in low-ENL excreters were detected. Functional analysis identified four common upstream regulators (master genes): CD3, IFNG, IGF1 and TNFRSF1A. Our findings suggest that the enhanced conversion of flaxseed lignan to ENL is associated with a suppressed inflammatory status. Full article

In this work, milk samples collected in a cohort of intensive dairy farms of the Po Valley (Italy) were screened for their (poly)-phenolic profile to check the occurrence of phenolic metabolites of biological interest. The selected dairy farms were previously classified on the basis of their cow feeding system, considering the utilization of corn silage as the main ingredient of the rations. Overall, ultra-high-pressure liquid chromatography coupled with mass spectrometry using an Orbitrap analyzer, followed by unsupervised and supervised statistics, allowed identifying clear different phenolic distributions in the milk samples. Accordingly, a great variability in the phenolic profiles of the different milk samples was observed, with two main phenolic clusters outlined by the unsupervised hierarchical clustering approach and not fully correlated to the nutritional strategy considered. The variables’ importance in the projection approach allowed selecting the most important metabolites, resulting in samples’ discrimination. Among the most discriminative compounds, we found phenolic metabolites (such as hippuric acid and 4-hydroxyhippuric acid), followed by lignans (such as enterolactone) and isoflavonoids (such as equol and O-desmethylangolensin). Taken together, our findings suggested that both the feeding systems and the ability of dairy cows to process parent phenolic compounds were the main factors providing the final (poly)-phenolic profile of the milk samples. Future targeted and ad hoc studies appear of great interest to evaluate the potential biological effects of these compounds on cow health. Full article

The study aims to examine the association of dietary intake of lignans with the risk of hip fractures in Chinese older adults. This was a 1:1 age- and gender- matched case–control study. Dietary survey was conducted by face-to-face interviews using a 79-item validated food frequency questionnaire. Habitual intake of total and individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) was estimated based on the available lignans databases. Conditional logistic regression was used to examine the relationship of dietary total and individual lignans, lignan-rich foods (vegetables, fruits, nuts, and cereals) and dietary fibers with the risk of hip fracture. A total of 1070 pairs of hip fracture incident cases and controls were recruited. Compared with the lowest quartile, the highest quartile group showed a reduced hip fracture risk by 76.3% (0.237, 95% CI: 0.103–0.544, P_trend < 0.001) for total lignans, and 62.5% (0.375, 95% CI: 0.194–0.724, P_trend = 0.001) for dietary fibers. Similar findings were observed for individual lignans, the estimated enterolactone level, as well as lignans from vegetables and nuts. We concluded that greater consumption of total and individual lignans, and lignan-rich foods were significantly associated with decreased risk of hip fracture. Full article