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The precision nutrition paradigm is based on the premise that substantial variation exists between human subjects in terms of diet-related disease risk and response to dietary interventions. In terms of better defining, 'the right diet for the right person at the right time' may be more appropriate than 'one-diet-fits-all'. This review will explore how systems biology and nutrigenomics approaches have advanced the precision nutrition paradigm. We will draw upon a number of elegant mechanistic studies that have enhanced our understanding with respect to the complex biology and inter-organ crosstalk, relating to inflammation and metabolism, that underpin cardio-metabolic health. Also, this review will explore the extent to which more targeted, precision nutrition approaches may attenuate adverse risk factors associated with cardio-metabolic disease. We will focus on the key characteristics or 'metabotypes' of high- low-risk individuals and response non-response to interventions, to generate greater insights with respect to risk stratification and therapeutic interventions to enhance disease prevention. The goal is to utilise systems biology to enhance understanding by underpinning more targeted nutritional approaches, which may improve efficacy of personalised nutrition interventions.

There is a need to transform our current food system if we are to feed the rapidly expanding global population while maintaining planetary health. Within the island of Ireland, there is an urgent need to diversify the foods that currently contribute to our populations' protein intake. A Shared Island Innovative Food System approach is required to achieve this in a manner that is sustainable and provides benefits to producers, consumers and other supply chain participants. The Protein-I project employs such an approach, with the paradigm focusing on production of plant food through to human health, while paying particular attention to the development of the rural bioeconomy. Using an interdisciplinary approach, the team will develop strategies to maximise sustainable plant protein production in a traceable/transparent fashion and assess the impact of changes to existing value chains and the development of new value chains for the rural economy. A smart supply chain technology solution tailored to the needs of the agri-food industry will be developed and tested. Additionally, we will co-design consumer-led approaches to diversify plant protein intake, model the impact of changes at the population level and perform human interventions to demonstrate efficacy in terms of achieving adequate nutrition and improved health. Comprehensive engagement with stakeholders is embedded throughout the whole project to embrace the multi-actor approach. Overall, the project will be a key step towards future-proofing our food system on the island of Ireland and moving towards protecting planetary and population health, within the context of a just transition.

ScopeGut microbiota alterations are associated with obesity and type 2 diabetes. Yeast β-glucans are potential modulators of the innate immune-metabolic response, by impacting glucose, lipid, and cholesterol homeostasis. The study examines whether yeast β-glucan interacts differentially with either an obese healthy or obese diabetic gut microbiome, to impact metabolic health through hepatic effects under high-fat dietary challenge.Methods and resultsMale C57BL/6J mice are pre-inoculated with gut microbiota from obese healthy (OBH) or obese type 2 diabetic (OBD) subjects, in conjunction with a high-fat diet (HFD) with/without yeast β-glucan. OBD microbiome colonization adversely impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast β-glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD-induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast β-glucan supplementation.ConclusionsHepatic metabolism is adversely affected by OBD microbiome colonization with high-fat feeding, but partially resolved by yeast β-glucan. More targeted dietary interventions that encompass the interactions between diet, gut microbiota, and host metabolism may have greater treatment efficacy.

Protein supplementation is an attractive strategy to prevent loss of muscle mass in older adults. However, it could be counterproductive due to adverse effects on appetite. This systematic review and meta-analysis aimed to determine the effects of protein supplementation on appetite and/or energy intake (EI) in healthy older adults. MEDLINE, The Cochrane Library, CINAHL, and Web of Science were searched up to June 2020. Acute and longitudinal studies in healthy adults ≥60 y of age that reported effects of protein supplementation (through supplements or whole foods) compared with control and/or preintervention (for longitudinal studies) on appetite ratings, appetite-related peptides, and/or EI were included. Random-effects model meta-analysis was performed on EI, with other outcomes qualitatively reviewed. Twenty-two studies (9 acute, 13 longitudinal) were included, involving 857 participants (331 males, 526 females). In acute studies (n = 8), appetite ratings were suppressed in 7 out of 24 protein arms. For acute studies reporting EI (n = 7, n = 22 protein arms), test meal EI was reduced following protein preload compared with control [mean difference (MD): −164 kJ; 95% CI: −299, −29 kJ; P = 0.02]. However, when energy content of the supplement was accounted for, total EI was greater with protein compared with control (MD: 649 kJ; 95% CI: 438, 861 kJ; P

Metabolic inflammation (metaflammation) is characteristic of obesity-related metabolic disorders, associated with increased risk of development of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), or cardiovascular disease. Metaflammation refers to a chronic, low-grade systemic inflammation as opposed to the classical transient and acute inflammatory responses of the innate immune system. Metaflammation is driven by a range of adverse dietary factors, including saturated fatty acids and some sugars, suggesting that certain dietary triggers may be particularly relevant beyond simple excessive dietary intake presenting as obesity. Importantly, obese patients with diabetes have a higher risk of infection and display gut microbiota profiles characteristic of dysfunctional immunity. Targeting metaflammation has also emerged as a strategy to attenuate metabolic disease. In this review we explore how different nutrition interventions may reconfigure disrupted metabolic inflammation in type 2 diabetes and nonalcoholic fatty liver disease by reestablishing a conventional proinflammatory program in innate immune cells and/or correcting dysbiosis to dampen systemic inflammation. We begin by reviewing concepts of metabolic inflammation relating to IL-1β inflammation and how it is induced by dietary and/or metabolic stressors. We then explore whether and how dietary interventions may attenuate processes pertaining to metaflammation, either directly or indirectly via the microbiome. Hence, we hope to bring new perspectives to alleviate the metaflammation typifying metabolic disease.

Preliminary evidence has suggested that high-fat diets (HFD) enriched with SFA, but not MUFA, promote hyperinsulinaemia and pancreatic hypertrophy with insulin resistance. The objective of this study was to determine whether the substitution of dietary MUFA within a HFD could attenuate the progression of pancreatic islet dysfunction seen with prolonged SFA-HFD. For 32 weeks, C57BL/6J mice were fed either: (1) low-fat diet, (2) SFA-HFD or (3) SFA-HFD for 16 weeks, then switched to MUFA-HFD for 16 weeks (SFA-to-MUFA-HFD). Fasting insulin was assessed throughout the study; islets were isolated following the intervention. Substituting SFA with MUFA-HFD prevented the progression of hyperinsulinaemia observed in SFA-HFD mice (P< 0·001). Glucose-stimulated insulin secretion from isolated islets was reduced by SFA-HFD, yet not fully affected by SFA-to-MUFA-HFD. Markers ofβ-cell identity (Ins2,Nkx6.1,Ngn3,Rfx6,Pdx1andPax6) were reduced, and islet inflammation was increased (IL-1β, 3·0-fold,P= 0·007; CD68, 2·9-fold,P= 0·001;Il-6, 1·1-fold,P= 0·437) in SFA-HFD – effects not seen with SFA-to-MUFA-HFD. Switching to MUFA-HFD can partly attenuate the progression of SFA-HFD-induced hyperinsulinaemia, pancreatic inflammation and impairments inβ-cell function. While further work is required from a mechanistic perspective, dietary fat may mediate its effect in an IL-1β–AMP-activated protein kinaseα1-dependent fashion. Future work should assess the potential translation of the modulation of metabolic inflammation in man.

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research.

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.

Introduction High-fat diet (HFD)-induced obesity impairs clearance of cholesterol through the Reverse Cholesterol Transport (RCT) pathway, with downregulation in hepatic expression of cholesterol and bile acid transporters, namely ABCG5/8 and ABCB11, and reduced high-density lipoprotein (HDL) cholesterol efflux capacity (CEC). In the current study, we hypothesized that the development of hepatosteatosis, secondary to adipose-tissue dysfunction, contributes to obesity-impaired RCT and that such effects could be mitigated using the anti-inflammatory drug sodium salicylate (NaS). Materials and methods C57BL/6J mice, fed HFD ± NaS or low-fat diet (LFD) for 24 weeks, underwent glucose and insulin tolerance testing. The 3H-cholesterol movement from macrophage-to-feces was assessed in vivo. HDL-CEC was determined ex vivo. Cytokine secretion from adipose-derived stromal vascular fraction (SVF) cells was measured ex vivo. Liver and HDL proteins were determined by mass spectrometry and analyzed using Ingenuity Pathway Analysis. Results NaS delayed HFD-induced weight gain, abrogated priming of pro-IL-1β in SVFs, attenuated insulin resistance, and prevented steatohepatitis (ectopic fat accumulation in the liver). Prevention of hepatosteatosis coincided with increased expression of PPAR-alpha/beta-oxidation proteins with NaS and reduced expression of LXR/RXR-induced proteins including apolipoproteins. The latter effects were mirrored within the HDL proteome in circulation. Despite remarkable protection shown against steatosis, HFD-induced hypercholesterolemia and repression of the liver-to-bile cholesterol transporter, ABCG5/8, could not be rescued with NaS. Discussions and conclusions The cardiometabolic health benefits of NaS may be attributed to the reprogramming of hepatic metabolic pathways to increase fatty acid utilization in the settings of nutritional overabundance. Reduced hepatic cholesterol levels, coupled with reduced LXR/RXR-induced proteins, may underlie the lack of rescue of ABCG5/8 expression with NaS. This remarkable protection against HFD-induced hepatosteatosis did not translate to improvements in cholesterol homeostasis., Graphical abstract Image 1, Highlights • Sodium salicylate (NaS) initially delays weight-gain in mice fed high-fat diet (HFD) - catch-up evident in weeks 12–24. • NaS prevents HFD-induced insulin resistance, hepatosteatosis and pro-IL-1β priming in adipose tissue even upon weight-gain. • Hepatic expression of proteins involved in beta oxidation, oxidative phosphorylation and TCA cycle upregulated with NaS. • Hepatic expression of LXR/RXR proteins eg. apolipoproteins reduced with NaS; these effects were mirrored in HDL proteome. • NaS failed to improve HFD-impaired Reverse Cholesterol Transport or hypercholesterolemia despite preventing hepatosteatosis.

International audience; Older adults with poor appetite are at higher risk of undernutrition due to the role of appetite as a key driver of food intake. Dietary protein and fibre are critical nutrients in this population, and enhancing their intake is vital to preventing undernutrition and maintaining organ function and health. In APPETITE, a transdisciplinary consortium of experts from eight institutions in six European countries will collaborate to design potentially effective interventions to enhance protein and fibre consumption of community-dwelling older adults with poor appetite, thereby addressing undernutrition through a targeted nutrition- and physical activity-based strategy. Older adults with poor appetite will first be evaluated using a mixed-methods approach to gain insights into their nutritional and behavioural preferences. Working with this target group, innovative, acceptable and affordable food products will be developed that combine several domestic plant proteins and dietary fibres. Mechanistic insights will be gained by examining the impact of selected products and physical activity on digestibility, amino acid bioavailability and whole-body protein metabolism. In a multi-country, randomised controlled intervention trial, the impact of two new food products, provided as part of a personalised diet, a physical activity programme, and their combination will be determined. APPETITE will improve our understanding about plant-based protein and fibre products and their metabolic and clinical effects. It will create new knowledge about how these products can be combined in a whole-diet approach, together with physical activity and regular social contacts, to overcome undernutrition and to contribute to a better quality of life for older Europeans.

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.

Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.

Background: Leucine-enriched protein (LEU-PRO) and long-chain(LC) n–3 (ω–3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone.Objective: The impact of LEU-PRO supplementation alone and combined with LC n–3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis(MyoPS) was investigated in older adults at risk of sarcopenia.Methods: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO(3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n–3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n–3; n = 38),or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28).Results: Neither LEU-PRO nor LEU-PRO+n–3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: −7.1 Nm; 95% CI: −12.5,−1.8 Nm; P < 0.01) was lower post supplementation in LEUPRO+n–3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n–3 compared with CON postsupplementation (allP < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n–3 postsupplementation compared with CON (all P < 0.05).Conclusions: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n–3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov asNCT03429491.

Objective Impaired insulin secretion and action contribute to the development of type 2 diabetes. Dietary fat modification may improve insulin sensitivity, whereas the effect on insulin secretion is unclear. We investigated the effect of dietary fat modification on insulin secretion in subjects with the metabolic syndrome. Design In a 12-week pan-European parallel, randomized controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to four isoenergetic diets: high-fat diets rich in saturated fat (HSFA) or monounsaturated fat (HMUFA) or low-fat, high-complex carbohydrate diets with (LFHCC n-3) or without (LFHCC control) 1.2 g/day of n-3 PUFA supplementation. Insulin secretion was estimated as acute insulin response to glucose (AIRg) and disposition index (DI), modeled from an intravenous glucose tolerance test. Results There were no overall effect of the dietary intervention on AIRg and DI in the total cohort, in neither the high-fat nor LFHCC groups. We observed significant diet*fasting glucose category interactions for AIRg (P = 0.021) and DI (P = 0.001) in the high-fat groups. In subjects with normal fasting glucose and preserved first phase insulin secretion, the HMUFA diet increased, whereas the HSFA diet reduced AIRg (P = 0.015) and DI (P = 0.010). Conclusions The effects of dietary fat modification on insulin secretion were minor, and only evident in normoglycemic subjects. In this case, the HMUFA diet improved AIRg and DI, as compared to the HSFA diet.

Background: Oesophageal Adenocarcinoma (OAC) is the most strongly associated cancer with obesity. Approximately 75% of OAC patients are obese which results in chronic systemic low-grade inflammation, which is believed to drive carcinogenesis as well as influencing radiation treatment response. Adipose tissue is a regulatory organ with many downstream effects which are still not understood. This study aims to elucidate what influence adipose tissue metabolism and secretome have in treatment resistance and whether obesity alters this response. Methods: Following patient consent, ex-vivo Visceral Adipose Tissue (VAT) explants were exposed to increasing doses of radiation with/without Palmitate and Oleate. Agilent Seahorse Xfe24 was used to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in VAT explants and mitochondrial metabolic parameters in dendritic cells (DCs) following treatment with Adipose Conditioned Media (ACM). Levels of DC maturation following irradiated ACM exposure and Macrophage (Mɸ) polarisation following ACM or Tumour Conditioned Media (TCM) exposure were analyzed by flow cytometry. Irradiated ACM and TCM were analyzed via MSD 54plex ELISA to assess secreted factors on angiogenic, chemokine, cytokine, inflammatory, TH17 or vascular injury panels. Results: VAT explant energy metabolism showed a significant increase for OCR and ECAR with obesity and increasing radiation exposure however OCR was significantly decreased following Palmitate treatment compared with untreated and Oleate treated adipose explants (p Conclusion: We have demonstrated that obesity and increasing radiation doses can significantly alter the immune-metabolic influences of adipose tissue and further studies are profiling the lipidomic and metabolomic landscape of the adipose secretome. Alterations in the secretome of adipose tissue could potentiate the tumor microenvironment and deleteriously affect immune cell function therefore further interrogation is required to fully elucidate the influence adipose tissue may have in treatment response. Citation Format: Fiona O'Connell, Eimear Mylod, Ailsing B. Heeran, Noel E. Donlon, Maria Davern, Christine Butler, Anshul Bhardwaj, Claire Donohoe, Narayanasamy Ravi, John V. Renyolds, Margaret R. Dunne, Helen M. Roche, Jacintha O'Sullivan. Exploring the immune-metabolic mechanisms of adipose tissue in oesophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1990.

Scope Combining different “omics” data types in a single, integrated analysis may better characterize the effects of diet on human health. Methods and results The performance of two data integration tools, similarity network fusion tool (SNFtool) and Data Integration Analysis for Biomarker discovery using Latent variable approaches for “Omics” (DIABLO; MixOmics), in discriminating responses to diet and metabolic phenotypes is investigated by combining transcriptomics and metabolomics datasets from three human intervention studies: a postprandial crossover study testing dairy foods (n = 7; study 1), a postprandial challenge study comparing obese and non‐obese subjects (n = 13; study 2); and an 8‐week parallel intervention study that assessed three diets with variable lipid content on fasting parameters (n = 39; study 3). In study 1, combining datasets using SNF or DIABLO significantly improve sample classification. For studies 2 and 3, the value of SNF integration depends on the dietary groups being compared, while DIABLO discriminates samples well but does not perform better than transcriptomic data alone. Conclusion The integration of associated “omics” datasets can help clarify the subtle signals observed in nutritional interventions. The performance of each integration tool is differently influenced by study design, size of the datasets, and sample size., “Omics” technologies like metabolomics or transcriptomics can give different snapshots of the molecular changes that are associated with diet. However, combining such “omics” data, may offer a deeper understanding of the holistic effects of nutrition on biological processes. The authors explore, in three independent diet‐related studies, how two different data integration tools can help to identify diet‐related molecular signatures.

Background Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases. Objectives We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia. Methods Postprandial (0–6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18–65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected. Results The postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort. Conclusions The variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation–related diseases. This trial was registered at clinicaltrials.gov as NCT03479866.

As COVID-19 continues to spread worldwide, severe disease and mortality have been observed in obese patients. We discuss how obesity and obesity-associated factors such as ‘meta-flammation’, dietary fat intake and paradoxical suppression of the innate immune response within the pulmonary compartment may be crucial determinants in the host response to a novel viral pathogen. Modulation of immune cell bioenergetics and metabolic potential plays a central role in the innate immune response to infection, and as we strive to combat this new global health threat, immunometabolism of the innate immune system warrants attention.

Sarcopenic obesity is characterised by the double burden of diminished skeletal muscle mass and the presence of excess adiposity. From a mechanistic perspective, both obesity and sarcopenia are associated with sub-acute, chronic pro-inflammatory states that impede metabolic processes, disrupting adipose and skeletal functionality, which may potentiate disease. Recent evidence suggests that there is an important cross-talk between metabolism and inflammation, which has shifted focus upon metabolic-inflammation as a key emerging biological interaction. Dietary intake, physical activity and nutritional status are important environmental factors that may modulate metabolic-inflammation. This paradigm will be discussed within the context of sarcopenic obesity risk. There is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation in sarcopenic obesity. Research suggests that there may be scope for the modulation of sarcopenic obesity with alterations in diet. The potential impact of increasing protein consumption and reconfiguration of dietary fat composition in human dietary interventions are evaluated. This review will explore emerging data with respect to if and how different dietary components may modulate metabolic-inflammation, particularly with respect to adiposity, within the context of sarcopenic obesity.

Lay Summary A person’s diet may impact inflammatory bowel disease (IBD) risk. IBD is an inflammatory condition. We explore how certain foods may trigger, or indeed attenuate, inflammation in some IBD patients, but not others. Greater knowledge is needed underpinning personalized nutrition within effective medical management.

peer-reviewed Impaired insulin secretion and action are important for development of type 2 diabetes (T2D) and metabolic syndrome (MetS). Despite recognized heterogeneity of these glucometabolic disorders, few data are available of biological variation in insulin secretion and action among individuals with T2D and MetS. The aim of this study was to explore the inter-individual variations using gold standard methods in a cross-sectional study of two independent cohorts of phenotypically well-characterized subjects. Cohort I included 486 subjects with MetS, and cohort II 62 subjects with established T2D. First phase insulin secretion was defined as the incremental area under the curve 0–8 min (iAUC0–8 min) during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured as the insulin sensitivity index (SI) modelled from IVGTT in cohort I, and in II as total glucose disposal (TGD) estimated from a euglycaemic-hyperinsulinaemic clamp. Variation is given as total range and, fold-variation between 5%- and 95%-percentile. The iAUC0–8min ranged from 60 to 3397mUL 1min 1 among subjects with MetS and from 263 to 1194mUL 1min 1 in subjects with T2D, representing a more than 10-fold variation. Insulin sensitivity ranged from SI 0.19 to 15.29 (mU/L) 1min 1 among subjects with MetS and TGD 12.9–101.6 lmolkgFFM 1min 1 in subjects with T2D, representing a 6.8 and 5.5- fold variation, respectively. The other components of MetS; BMI, waist-hip ratio, HDL-cholesterol, triglycerides and blood pressure (BP), showed a 1.4–4.7-fold variation. In conclusion, our data demonstrated extensive inter-individual variations in insulin secretion and sensitivity. These variations may be essential to take into account when planning clinical research and treatment in subjects with T2D and MetS.

Reduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

Sarcopenia is a muscle disease rooted in adverse muscle changes that accrue across a lifetime. It is an independent risk factor for numerous adverse health outcomes. In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a definition for the identification of people with sarcopenia (EWGSOP1). In 2018, this definition was updated based on the newest evidence (EWGSOP2), with the focus now on low muscle strength rather than low muscle quantity as the key characteristic of sarcopenia. In addition, EWGSOP2 provides clear cut-off points for measurements of variables that identify sarcopenia. The aim of this study was to determine the prevalence of sarcopenia among community-dwelling older adults in Ireland for the first time and to assess agreement between the EWGSOP1 and EWGSOP2 definitions. In a cross-sectional analysis, 490 community-dwelling adults (age 78.4 ± 8.0 y, body mass index 27.6 ± 5.1 kg/m2) were assessed. Skeletal muscle mass was estimated using bioelectrical impedance analysis, muscle strength was measured via handgrip dynamometry and physical performance via the Short Physical Performance Battery. Sarcopenia was defined according to both the 2010 criteria (EWGSOP1) and the updated 2018 criteria (EWGSOP2). Using the EWGSOP1 criteria, the prevalence of sarcopenia was 7.1% (2.6% sarcopenia, 4.5% severe sarcopenia) and 3.6% were classified as pre-sarcopenic (low muscle mass without a decrement in strength or physical performance). Using the EWGSOP2 criteria, the prevalence of sarcopenia was 5.5% (1.6% sarcopenia, 3.9% severe sarcopenia) and 23.4 % were classified as having low strength but without a decrement in muscle mass. Five of the participants who were classified as sarcopenic (2 sarcopenia, 3 severe sarcopenia) by EWGSOP1 were classified as “normal” using the EWGSOP2 criteria. In conclusion, the prevalence of sarcopenia in community-dwelling older adults in Ireland is in line with the prevalence reported in other European countries using the EWGSOP1 criteria (3.3–11.4 %). To our knowledge this is the first study to compare the prevalence based on the EWGSOP1 and the EWGSOP2 criteria. We report a slightly lower prevalence using the EWGSOP2 definition compared to the EWGSOP1 definition. Importantly however, in contrast to EWGSOP1, the EWGSOP2 definition identified a substantial proportion of older adults with poor strength in the absence of overt sarcopenia (23.4%). These older adults represent a group who would benefit from further clinical investigation and intervention.

Introductionβ-glucans are naturally occurring polysaccharides which have isoform specific immunomodulatory and metabolic properties(1). Certain yeast (1→3)-β-D-glucan isoforms improve cholesterol(2), glucose(3) and lipid homeostasis(4). Feeding (1→3)-β-D-glucan alters the microbiome of high-fat diet (HFD) induced obese (DIO)/type 2 diabetic (T2D) mice(5). Here we investigated the potential impact of baker's yeast (1→3)-β-D-glucan in mice humanized with gut microbiomes from either obese healthy versus obese diabetic subjects on immune-metabolism within the context of high-fat feeding.MethodsC57Bl/6J male mice received an antibiotic cocktail of Ampicillin, Metronidazole, Vancomycin, Imipenem and Ciprofloxacin HCl in their drinking water for 6 weeks to diminish the endogenous gut microbiota. Mice were inoculated with microbiota samples obtained from obese healthy (OBH) or diabetic (OBD) humans twice daily for 3 days by oral dosing. Mice were fed a low-fat diet (LFD) (10% kcal) for 4 weeks followed by HFD (45% kcal) with/without baker's yeast (1→3)-β-D-glucan (βG), for 9 weeks. Weight, feed intake, glucose tolerance (1.5g/kg), insulin tolerance (0.5U/kg), hepatic and skeletal lipid levels were examined. Tissue specific molecular markers of metabolism and inflammation, and gut microbiome analysis are being determined to compliment the phenotypic data.ResultsOBH mice were more glucose tolerant and insulin sensitive than OBD mice, despite equal weight gain and adipose tissue mass. Fasting HOMA-IR, attributable to higher insulin concentrations, was higher in OBD compared to OBH mice. βG supplementation reduced HOMA-IR in OBD mice (P < 0.0611). Hepatic triacylglycerol (TAG) and cholesterol levels were also higher in OBD mice, which were prevented by βG supplementation. Hepatic proteomic, caecal microbiomic and metabolomic analysis is on-going in order to ascertain the impact of the OBD versus OBH dysbosis with/without βG supplementation with specific attention on immune-metabolism.

Objective:To apply a dietary modelling approach to investigate the impact of substituting beef intakes with three types of alternative fatty acid (FA) composition of beef on population dietary fat intakes.Design:Cross-sectional, national food consumption survey – the National Adult Nutrition Survey (NANS). The fat content of the beef-containing food codes (n 52) and recipes (n 99) were updated with FA composition data from beef from animals receiving one of three ruminant dietary interventions: grass-fed (GRASS), grass finished on grass silage and concentrates (GSC) or concentrate-fed (CONC). Mean daily fat intakes, adherence to dietary guidelines and the impact of altering beef FA composition on dietary fat sources were characterised.Setting:Ireland.Participants:Beef consumers (n 1044) aged 18–90 years.Results:Grass-based feeding practices improved dietary intakes of a number of individual FA, wherein myristic acid (C14 : 0) and palmitic acid (C16 : 0) were decreased, with an increase in conjugated linoleic acid (C18 : 2c9,t11) and trans-vaccenic acid (C18 : 1t11; P < 0·05). Improved adherence with dietary recommendations for total fat (98·5 %), SFA (57·4 %) and PUFA (98·8 %) was observed in the grass-fed beef scenario (P < 0·001). Trans-fat intakes were increased significantly in the grass-fed beef scenario (P < 0·001).Conclusions:To the best of our knowledge, the present study is the first to characterise the impact of grass-fed beef consumption at population level. The study suggests that habitual consumption of grass-fed beef may have potential as a public health strategy to improve dietary fat quality.

Evidence suggests that processed red meat consumption is a risk factor for CVD and type 2 diabetes (T2D). This analysis investigates the association between dietary patterns, their processed red meat contributions, and association with blood biomarkers of CVD and T2D, in 786 Irish adults (18–90 years) using cross-sectional data from a 2011 national food consumption survey. All meat-containing foods consumed were assigned to four food groups (n 502) on the basis of whether they contained red or white meat and whether they were processed or unprocessed. The remaining foods (n 2050) were assigned to twenty-nine food groups. Two-step and k-means cluster analyses were applied to derive dietary patterns. Nutrient intakes, plasma fatty acids and biomarkers of CVD and T2D were assessed. A total of four dietary patterns were derived. In comparison with the pattern with lower contributions from processed red meat, the dietary pattern with greater processed red meat intakes presented a poorer Alternate Healthy Eating Index (21·2 (sd 7·7)), a greater proportion of smokers (29 %) and lower plasma EPA (1·34 (sd 0·72) %) and DHA (2·21 (sd 0·84) %) levels (P

Epidemiology and clinical studies provide clear evidence of the complex links between diet and health. To understand these links, reliable dietary assessment methods are pivotal. Biomarkers have emerged as more objective measures of intake compared with traditional dietary assessment methods. However, there are only a limited number of putative biomarkers of intake successfully identified and validated. The use of biomarkers that reflect food intake to examine diet related diseases represents the next step in biomarker research. Therefore, the aim of this study was to (1) identify and confirm biomarkers associated with dietary fat intake and (2) examine the relationship between those biomarkers with health parameters. Heatmap analysis identified a panel of 22 lipid biomarkers associated with total dietary fat intake in the Metabolic Challenge (MECHE) Study. Confirmation of four of these biomarkers demonstrated responsiveness to different levels of fat intake in a separate intervention study (NutriTech study). Linear regression identified a significant relationship between the panel of dietary fat biomarkers and HOMA-IR, with three lipid biomarkers (C16, PCaaC36:2, and PCae36:4) demonstrating significant associations. Identifying such links allows us to explore the relationship between diet and health to determine whether these biomarkers can be modulated through diet to improve health outcomes. Department of Agriculture, Food and the Marine

Scope Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL-1 beta inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may alter T2D risk factors. Methods Meta-analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3-related single-nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance. Results SFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL(-1) (SE +/- 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (beta +/- SE = -0.0058 +/- 0.002, p = 0.004) to increase insulin by 0.0058 IU mL(-1), per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression. Conclusion Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants.