The exposome, defined as the cumulative measure of external exposures and associated biological responses throughout the lifespan, has emerged in recent years as a cornerstone in biomedical sciences. ...Metabolomics stands out here as one of the most powerful tools for investigating the interplay between the genetic background, exogenous, and endogenous factors within human health. However, to address the complexity of the exposome, novel methods are needed to characterize the human metabolome. In this work, we have optimized and validated a multianalyte metabolomics platform for large-scale quantitative exposome research in plasma and urine samples, based on the use of simple extraction methods and high-throughput metabolomic fingerprinting. The methodology enables, for the first time, the simultaneous characterization of the endogenous metabolome, food-related metabolites, pharmaceuticals, household chemicals, environmental pollutants, and microbiota derivatives, comprising more than 1000 metabolites in total. This comprehensive and quantitative investigation of the exposome is achieved in short run times, through simple extraction methods requiring small-sample volumes, and using integrated quality control procedures for ensuring data quality. This metabolomics approach was satisfactorily validated in terms of linearity, recovery, matrix effects, specificity, limits of quantification, intraday and interday precision, and carryover. Furthermore, the clinical potential of the methodology was demonstrated in a dietary intervention trial as a case study. In summary, this study describes the optimization, validation, and application of a multimetabolite platform for comprehensive and quantitative metabolomics-based exposome research with great utility in large-scale epidemiological studies.
Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in ...hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.
Increasing evidence links intestinal permeability (IP), a feature of the intestinal barrier, to several pathological or dysfunctional conditions. Several host and environmental factors, including ...dietary factors, can affect the maintenance of normal IP. In this regard, food bioactives, such as polyphenols, have been proposed as potential IP modulators, even if the mechanisms involved are not yet fully elucidated. The aim of the present paper is to provide a short overview of the main evidence from in vitro and in vivo studies supporting the role of polyphenols in modulating IP and briefly discuss future perspectives in this research area.
The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key ...role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship “polyphenols ↔ microbiota” are still poorly understood. Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health.
Polyphenols and Health: Current State and Progress Tomás-Barberán, Francisco A; Andrés-Lacueva, Cristina
Journal of agricultural and food chemistry,
09/2012, Letnik:
60, Številka:
36
Journal Article
Recenzirano
During the 5th International Conference on Polyphenols and Health that was held in Sitges (Spain) in October 2011, the latest advances in this area of active research were presented. Sessions on ...polyphenol effects on cardiovascular disease, polyphenols as ingredients of functional foods, the role of polyphenols in preventing obesity and diabetes, the interaction of polyphenols with gut microbiota, bioavailability and metabolism of polyphenols in humans, the mechanisms of action of these metabolites in different models, new methodologies for the study of the role of polyphenols in health, polyphenols and cancer, recent developments in phenolic compounds and neuroscience, and polyphenols in epidemiology and public health were organized. This highlight issue presents a selection of papers from invited speakers, oral presentations, and poster prize winners. The perspectives for this exciting area of very active research were also discussed at the meeting and are summarized in this introductory paper.
The gut microbiota is involved in the regulation of the intestinal permeability (IP), whose disruption is a frequent condition in older people and is associated with the development of several ...diseases. The diet can affect the gut microbiota and IP, although the molecular mechanisms involved are unclear. Metabolomics is one of the suitable approaches to study the effects of diet on gut microbiota and IP, although, up to now, the research has focused only on a few dietary components. The aim here was to review the most recent literature concerning the application of metabolomics to the study of the diet-induced alterations of gut microbiota and the effects on IP, with a particular focus on the molecular pathways involved. An additional aim was to give a perspective on the future research involving dietary polyphenols, because despite their potential use in the management of increased IP, few studies have been reported to date.
Accurate dietary assessment is a challenge in nutritional research, needing powerful and robust tools for reliable measurement of food intake biomarkers. In this work, we have developed a novel ...quantitative dietary fingerprinting (QDF) approach, which enables for the first time the simultaneous quantitation of about 350 urinary food-derived metabolites, including (poly)phenolic aglycones, phase II metabolites, and microbial-transformed compounds, as well as other compounds (e.g., glucosinolates, amino acid derivatives, methylxanthines, alkaloids, and markers of alcohol and tobacco consumption). This method was fully validated for 220 metabolites, yielding good linearity, high sensitivity and precision, accurate recovery rates, and negligible matrix effects. Furthermore, 127 additional phase II metabolites were also included in this method after identification in urines collected from acute dietary interventions with various foods. Thus, this metabolomic approach represents one-step further toward precision nutrition and the objective of improving the accurateness and comprehensiveness in the assessment of dietary patterns and lifestyles.
Our health and well‐being are affected by our food systems. The new nutrition reality has been linked to complex food systems, interrelated with several pathways and determinants, including physical, ...socioeconomic, environmental, and ecological, and lately, has been strongly associated with population health, the increase in chronic diseases, and climate change. We briefly comment on four pillars, namely food environments, food security, food supply, and safety and nutritional epidemiology, all of which are key determinants of food systems. We overview some highlights, challenges, and methodologies with a view to advancing food and nutrition science as an integrated field of research. By modifying food systems, we are able to improve the aging and well‐being of populations and the health of the planet. Trusted science, nutritional education, new scientific‐public communication, integrated policy, investment, food availability, and cultural strategies are all essential for creating better food systems. Perceptual blindness in nutrition must be transformed.
Scope
Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated ...with intestinal barrier integrity. Our aim is to study the changes in GM‐derived indoles during a polyphenol‐rich (PR) diet intervention in older adults.
Methods and Results
Randomized, controlled, crossover trial in adults ≥ 60 years living in a residential care facility during an 8‐week PR versus control diet (n = 51). Seven GM‐tryptophan metabolites are measured in serum, and metataxonomic analysis of GM is performed on fecal samples. Exploratory subgroup analyses are performed based on renal function (RF). The PR‐diet significantly increases serum indole 3‐propionic acid (IPA) in subjects with normal RF, but not in subjects with impaired RF. Other GM‐tryptophan metabolites are not affected. Comparison of baseline GM composition shows shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA are associated with changes in C‐reactive protein (β = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p < 0.001) and Enterobacteriales (r = −0.15, p < 0.05) orders.
Conclusion
A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults.
Trial registration number: ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981).
In a randomized, controlled, crossover trial involving 51 adults ≥ 60 y receiving a PR‐diet for 8 weeks we observed that the PR‐diet significantly increased serum indole 3‐propionic acid (IPA), and the effect was dependent on renal function. During the trial, variation of IPA in volunteers with normal renal function was associated with changes in C‐reactive protein and gut microbiota, particularly with the Clostridiales and Enterobacteriales orders.
Polyphenols have great potential in regulating intestinal health and ameliorating pathological conditions related to increased intestinal permeability (IP). However, the efficacy of dietary ...interventions with these phytochemicals may significantly be influenced by interindividual variability factors affecting their bioavailability and consequent biological activity. In the present study, urine samples collected from older subjects undergoing a crossover intervention trial with polyphenol-rich foods were subjected to metabolomics analysis for investigating the impact of increased IP on the bioavailability of polyphenols. Interestingly, urinary levels of phase II and microbiota-derived metabolites were significantly different between subjects with healthier intestinal barrier integrity and those with increased IP disruption. Our results support that this IP-dependent impaired bioavailability of polyphenols could be attributed to disturbances in the gut microbial metabolism and phase II methylation processes. Furthermore, we also observed that microbiota-derived metabolites could be largely responsible for the biological activity elicited by dietary polyphenols against age-related disrupted IP.
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