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Diet, Gut Microbiota and Non-Alcoholic Fatty Liver Disease: Three Parts of the Same Axis

Cells

Sergio Quesada-Vázquez, Gerard Aragonès, Josep M Del Bas, & Xavier Escoté

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common liver disease in the world. NAFLD is principally characterized by an excessive fat accumulation in the hepatocytes. Diet is considered as one of the main drivers to modulate the composition of gut microbiota, which participate in different processes, affecting human metabolism. A disruption in the homeostasis of gut microbiota may lead to dysbiosis, which is commonly reflected by a reduction of the beneficial species and an increment in pathogenic microbiota. Gut and liver are in close relation due to the anatomical and functional interactions led by the portal vein, thus altered intestinal microbiota might affect liver functions, promoting inflammation, insulin resistance and steatosis, which is translated into NAFLD. This review will highlight the association between diet, gut microbiota and liver, and how this axis may promote the development of NAFLD progression, discussing potential mechanisms and alterations due to the dysbiosis of gut microbiota. Finally, it will revise the variations in gut microbiota composition in NAFLD, and it will focus in specific species, which directly affect NAFLD progression.

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Extracellular flux analyses reveal differences in mitochondrial PBMC metabolism between high-fit and low-fit females

American Journal – Endocrinology and Metabolism

Joëlle J. E. Janssen; Bart Lagerwaard; Mojtaba Porbahaie; Arie G. Nieuwenhuizen; Huub F. J. Savelkoul; R. J. Joost van Neerven; Jaap KeijerVincent C. J. de Boer

Analyzing metabolism of peripheral blood mononuclear cells (PBMCs) can possibly serve as a cellular metabolic read-out for lifestyle factors and lifestyle interventions. However, the impact of PBMC composition on PBMC metabolism is not yet clear, neither is the differential impact of a longer-term lifestyle factor versus a short-term lifestyle intervention. We investigated the effect of aerobic fitness level and a recent exercise bout on PBMC metabolism in females. PBMCs from 31 young female adults divided into a high-fit (V̇o2peak ≥ 47 mL/kg/min, n = 15) and low-fit (V̇o2peak ≤ 37 mL/kg/min, n = 16) groups were isolated at baseline and overnight after a single bout of exercise (60 min, 70% V̇o2peak). Oxygen consumption rate (OCR) and glycolytic rate (GR) were measured using extracellular flux (XF) assays and PBMC subsets were characterized using fluorescence-activated cell sorting (FACS). Basal OCR, FCCP-induced OCR, spare respiratory capacity, ATP-linked OCR, and proton leak were significantly higher in high-fit than in low-fit females (all P < 0.01), whereas no significant differences in glycolytic rate (GR) were found (all P > 0.05). A recent exercise bout did not significantly affect GR or OCR parameters (all P > 0.05). The overall PBMC composition was similar between high-fit and low-fit females. Mitochondrial PBMC function was significantly higher in PBMCs from high-fit than from low-fit females, which was unrelated to PBMC composition and not impacted by a recent bout of exercise. Our study reveals a link between PBMC metabolism and levels of aerobic fitness, increasing the relevance of PBMC metabolism as a marker to study the impact of lifestyle factors on human health.

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A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study

Clinical nutrition,

Mona A. Aldubayan, Kristina Pigsborg, Sophia M.O. Gormsen, Francisca Serra, Mariona Palou,  Sebastià Galmés, Andreu Palou-March, Claudia Favari, Mart Wetzels, Alberto Calleja, Miguel Angel Rodríguez Gomez, María Guirro Castellnou, Antoni Caimari, Mar Galofré, David Suñol, Xavier Escoté, Juan María Alcaide-Hidalgo, Josep M del Bas, Biotza Gutierrez, Thure Krarup, Mads F. Hjorth, Faidon Magkos

Background & aims

Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform—which uses metabolomic and genetic information to classify individuals into different ‘metabolic clusters’ and create personalized dietary plans—for improving health outcomes in subjects with overweight or obesity.

Methods

A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18–65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior.

Results

There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: −2.1 [95% CI -2.9, −1.4] kg; control: −2.0 [95% CI -2.7, −1.3] kg) and body weight (personalized: −3.1 [95% CI -4.1, −2.1] kg; control: −3.3 [95% CI −4.2, −2.4] kg). The difference between groups in fat mass change was −0.1 kg (95% CI −1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups.

Conclusion

Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities.

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A Systematic Review of Cost-Effectiveness Studies of Interventions With a Personalized Nutrition Component in Adults

Value In Health

Milanne M J Galekop; Carin A Uyl-de Groot; W Ken Redekop

Objectives: Important links between dietary patterns and diseases have been widely applied to establish nutrition interventions. However, knowledge about between-person heterogeneity regarding the benefits of nutrition intervention can be used to personalize the intervention and thereby improve health outcomes and efficiency. We performed a systematic review of cost-effectiveness analyses (CEAs) of interventions with a personalized nutrition (PN) component to assess their methodology and findings.

Methods: A systematic search (March 2019) was performed in 5 databases: EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. CEAs involving interventions in adults with a PN component were included; CEAs focusing on clinical nutrition or undernutrition were excluded. The CHEERS checklist was used to assess the quality of CEAs.

Results: We identified 49 eligible studies among 1792 unique records. Substantial variation in methodology was found. Most studies (91%) focused only on psychological concepts of PN such as behavior and preferences. Thirty-four CEAs were trial-based, 13 were modeling studies, and 4 studies were both trial- and model-based. Thirty-two studies used quality-adjusted life year as an outcome measure. Different time horizons, comparators, and modeling assumptions were applied, leading to differences in costs/quality-adjusted life years. Twenty-eight CEAs (49%) concluded that the intervention was cost-effective, and 75% of the incremental cost-utility ratios were cost-effective given a willingness-to-pay threshold of $50 000 per quality-adjusted life year.

Conclusions: Interventions with PN components are often evaluated using various types of models. However, most PN interventions have been considered cost-effective. More studies should examine the cost-effectiveness of PN interventions that combine psychological and biological concepts of personalization.

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Matrisome, innervation and oxidative metabolism affected in older compared with younger males with similar physical activity

Journal of Cachexia, Sarcopenia and Muscle

Bart Lagerwaard; Arie G. Nieuwenhuizen; Annelies Bunschoten;  Vincent C.J. de Boer; Jaap Keijer

Background: Due to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.

Methods: Eighteen older (69 ± 2.0 years) and 20 young (22 ± 2.0 years) males were recruited based on similar self-reported physical activity, which was verified using accelerometry measurements. Gene expression profiles of vastus lateralis biopsies obtained by RNA sequencing were compared, and key results were validated using quantitative polymerase chain reaction and western blot.

Results: Total physical activity energy expenditure was similar between the young and old group (404 ± 215 vs. 411 ± 189 kcal/day, P = 0.11). Three thousand seven hundred ninety-seven differentially expressed coding genes (DEGs) were identified (adjusted P-value cut-off of <0.05), of which 1891 were higher and 1906 were lower expressed in the older muscle. The matrisome, innervation and inflammation were the main upregulated processes, and oxidative metabolism was the main downregulated process in old compared with young muscle. Lower protein levels of mitochondrial transcription factor A (TFAM, P = 0.030) and mitochondrial respiratory Complexes IV and II (P = 0.011 and P = 0.0009, respectively) were observed, whereas a trend was observed for Complex I (P = 0.062), in older compared with young muscle. Protein expression of Complexes I and IV was significantly correlated to mitochondrial capacity in the vastus lateralis as measured in vivo (P = 0.017, R2 = 0.42 and P = 0.030, R2 = 0.36). A trend for higher muscle-specific receptor kinase (MUSK) protein levels in the older group was observed (P = 0.08).

Conclusions: There are clear differences in the transcriptome signatures of the vastus lateralis muscle of healthy older and young males with similar physical activity levels, including significant differences at the protein level. By disentangling physical activity and ageing, we appoint early skeletal muscle ageing processes that occur despite similar physical activity. Improved understanding of these processes will be key to design targeted anti-ageing therapies.

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Recommendations for standardizing nomenclature for dietary (poly)phenol catabolites

The American Journal of Clinical Nutrition 

Colin D Kay; Michael N Clifford; Pedro Mena; Gordon J McDougall; Cristina Andres-Lacueva; Aedin Cassidy; Daniele Del Rio; Nikolai Kuhnert; Claudine Manach; Gema Pereira-Caro; Ana Rodriguez-Mateos; Augustin Scalbert; Francisco Tomás-Barberán; Gary Williamson; David S Wishart; Alan Crozier

There is a lack of focus on the protective health effects of phytochemicals in dietary guidelines. Although a number of chemical libraries and databases contain dietary phytochemicals belonging to the plant metabolome, they are not entirely relevant to human health because many constituents are extensively metabolized within the body following ingestion. This is especially apparent for the highly abundant dietary (poly)phenols, for which the situation is compounded by confusion regarding their bioavailability and metabolism, partially because of the variety of nomenclatures and trivial names used to describe compounds arising from microbial catabolism in the gastrointestinal tract. This confusion, which is perpetuated in online chemical/metabolite databases, will hinder future discovery of bioactivities and affect the establishment of future dietary guidelines if steps are not taken to overcome these issues. In order to resolve this situation, a nomenclature system for phenolic catabolites and their human phase II metabolites is proposed in this article and the basis of its format outlined. Previous names used in the literature are cited along with the recommended nomenclature, International Union of Pure and Applied Chemistry terminology, and, where appropriate, Chemical Abstracts Service numbers, InChIKey, and accurate mass.

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Biomarkers of Nutrition and Health: New Tools for New Approaches

Nutrients Journal

Catalina Picó; Francisca Serra; Ana María Rodríguez; Andreu Palou; Jaap Keijer

A main challenge in nutritional studies is the valid and reliable assessment of food intake, as well as its effects on the body. Generally, food intake measurement is based on self-reported dietary intake questionnaires, which have inherent limitations. They can be overcome by the use of biomarkers, capable of objectively assessing food consumption without the bias of self-reported dietary assessment. Another major goal is to determine the biological effects of foods and their impact on health. Systems analysis of dynamic responses may help to identify biomarkers indicative of intake and effects on the body at the same time, possibly in relation to individuals’ health/disease states. Such biomarkers could be used to quantify intake and validate intake questionnaires, analyse physiological or pathological responses to certain food components or diets, identify persons with specific dietary deficiency, provide information on inter-individual variations or help to formulate personalized dietary recommendations to achieve optimal health for particular phenotypes, currently referred as “precision nutrition.” In this regard, holistic approaches using global analysis methods (omics approaches), capable of gathering high amounts of data, appear to be very useful to identify new biomarkers and to enhance our understanding of the role of food in health and disease.

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A systematic review of the cost-effectiveness of personalised interventions with a nutrition component in adults

ISPOR Conference (ISPOR)

Milanne Galekop(Ken) WK Redekop(Carin) CA Uyl – de Groot

Poster describeing the systematic literature review performed in the PREVENTOMICS project to establish what has already been done in personalised nutrition interventions and identify important gaps in literature.

This review will be used to design cross-sectional surveys and produce cost-effectiveness analyses to assess the efficiency of the PREVENTOMICS solution versus the current and alternative tools and assess its health outcomes and costs.

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Empowering consumers to PREVENT diet-related diseases through OMICS sciences (PREVENTOMICS): protocol for a parallel double-blinded randomised intervention trial to investigate biomarker-based nutrition plans for weight loss

BMJ Open

Mona Adnan Aldubayan; Kristina Pigsborg; Sophia M O Gormsen (University of Copenhagen); Francisca Serra; Mariona Palou (Univeristy of the Balearic Islands); Pedro Mena (University of Parma); Mart Wetzels (ONMI); Alberto Calleja (Carinsa); Antoni Caimari; Josep Del Bas; Biotza Gutierrez (Eurecat); Faidon Magkos; Mads Fiil Hjorth (University of Copenhagen)

Introduction: Personalised nutrition holds immense potential over conventional one-size-fits-all approaches for preventing and treating diet-related diseases, such as obesity. The current study aims to examine whether a personalised nutritional plan produces more favourable health outcomes than a standard approach based on general dietary recommendations in subjects with overweight or obesity and elevated waist circumference.

Methods and analysis: This project is a 10-week parallel, double-blinded randomised intervention trial. We plan to include 100 adults aged 18–65 years interested in losing weight, with body mass index ≥27 but<40 kg/m2 and elevated waist circumference (males >94 cm; females >80 cm). Participants will be categorised into one of five predefined ‘clusters’ based on their individual metabolic biomarker profile and genetic background, and will be randomised in a 1:1 ratio to one of two groups: (1) personalised plan group that will receive cluster-specific meals every day for 6 days a week, in conjunction with a personalised behavioural change programme via electronic push notifications; or (2) control group that will receive meals following the general dietary recommendations in conjunction with generic health behaviour prompts. The primary outcome is the difference between groups (personalised vs control) in the change in fat mass from baseline. Secondary outcomes include changes in weight and body composition, fasting blood glucose and insulin, lipid profile, adipokines, inflammatory biomarkers, and blood pressure. Other outcomes involve measures of physical activity and sleep patterns, health-related quality of life, dietary intake, eating behaviour, and biomarkers of food intake. The effect of the intervention on the primary outcome will be analysed by means of linear mixed models.

Ethics and dissemination: The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated through peer-reviewed publications, conference presentations and media outlets.

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Matrisome, innervation and oxidative metabolism affected in older compared with younger males with similar physical activity

Journal of Cachexia, Sarcopenia and Muscle: 12 pp. 1214–1231.

 Bart Lagerwaard; Arie G. Nieuwenhuizen; Annelies Bunschoten; Vincent C.J. de Boer; Jaap Keijer (Wageningen University & Research)

Background: Due to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.

Methods: Eighteen older (69 ± 2.0 years) and 20 young (22 ± 2.0 years) males were recruited based on similar self-reported physical activity, which was verified using accelerometry measurements. Gene expression profiles of vastus lateralis biopsies obtained by RNA sequencing were compared, and key results were validated using quantitative polymerase chain reaction and western blot.

Results: Total physical activity energy expenditure was similar between the young and old group (404 ± 215 vs. 411 ± 189 kcal/day, P = 0.11). Three thousand seven hundred ninety-seven differentially expressed coding genes (DEGs) were identified (adjusted P-value cut-off of <0.05), of which 1891 were higher and 1906 were lower expressed in the older muscle. The matrisome, innervation and inflammation were the main upregulated processes, and oxidative metabolism was the main downregulated process in old compared with young muscle. Lower protein levels of mitochondrial transcription factor A (TFAM, P = 0.030) and mitochondrial respiratory Complexes IV and II (P = 0.011 and P = 0.0009, respectively) were observed, whereas a trend was observed for Complex I (P = 0.062), in older compared with young muscle. Protein expression of Complexes I and IV was significantly correlated to mitochondrial capacity in the vastus lateralis as measured in vivo (P = 0.017, R2 = 0.42 and P = 0.030, R2 = 0.36). A trend for higher muscle-specific receptor kinase (MUSK) protein levels in the older group was observed (P = 0.08).

Conclusions: There are clear differences in the transcriptome signatures of the vastus lateralis muscle of healthy older and young males with similar physical activity levels, including significant differences at the protein level. By disentangling physical activity and ageing, we appoint early skeletal muscle ageing processes that occur despite similar physical activity. Improved understanding of these processes will be key to design targeted anti-ageing therapies.

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