Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial.

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults.

Background: Interesterification is an industrial processing technique used widely where hard fats are essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads. Objective: The aim of this study was to compare acute cardiovascular effects of functionally equivalent spreads (similar solid fat content) made with interesterified (IE) or non-IE palm-based fats, or spreadable butter. Methods: A randomised, controlled, 4-armed crossover, double-blind study (25 men, 25 women; 35-75 years; healthy; mean BMI 24.5, SD 3.8), compared effects of mixed nutrient meals containing 50 g fat from functionally equivalent products [IE spread, non-IE spread and spreadable butter (SB), with rapeseed oil (RO) as a reference treatment: with 16.7%, 27.9%, 19.3% and 4% palmitic acid, respectively] on 8 h postprandial changes in plasma triacylglycerol (TAG) and endothelial dysfunction (flow-mediated dilatation; FMD). Circulating reactive oxygen species (estimated using a neutrophil oxidative burst assay), glucose, insulin, NEFA, lipoprotein particle profiles, inflammatory markers (glycoprotein acetylation (Glyc-A) and IL-6), and biomarkers of endotoxemia were measured. Results: Postprandial plasma TAG concentrations after test meals were similar. However following RO versus the 3 spreads, there were significantly higher postprandial apolipoprotein B concentrations, and small HDL and LDL particle concentrations, and lower postprandial extra-large, large, and medium HDL particle concentrations, as well as smaller average HDL and LDL particle sizes. There were no differences following IE compared to the other spreads. Postprandial FMD% did not decrease after high-fat test meals, and there were no differences between treatments. Postprandial serum IL-6 increased similarly after test meals, but RO provoked a greater increase in postprandial concentrations of glycoprotein acetyls (GlycA), as well as 8 h sCD14, an endotoxemia marker. All other postprandial outcomes were not different between treatments. Conclusions: In healthy adults, a commercially-available IE-based spread did not evoke a different postprandial triacylglycerol, lipoprotein subclass, oxidative stress, inflammatory or endotoxemic response to functionally-equivalent, but compositionally-distinct alternative spreads. Clinical trial registry number: NCT03438084 (https://ClinicalTrials.gov).

Snack quality and snack timing are associated with cardiometabolic blood markers: the ZOE PREDICT study.

BACKGROUND: Snacking is a common diet behaviour which accounts for a large proportion of daily energy intake, making it a key determinant of diet quality. However, the relationship between snacking frequency, quality and timing with cardiometabolic health remains unclear. DESIGN: Demography, diet, health (fasting and postprandial cardiometabolic blood and anthropometrics markers) and stool metagenomics data were assessed in the UK PREDICT 1 cohort (N = 1002) (NCT03479866). Snacks (foods or drinks consumed between main meals) were self-reported (weighed records) across 2-4 days. Average snacking frequency and quality [snack diet index (SDI)] were determined (N = 854 after exclusions). Associations between snacking frequency, quality and timing with cardiometabolic blood and anthropometric markers were assessed using regression models (adjusted for age, sex, BMI, education, physical activity level and main meal quality). RESULTS: Participants were aged (mean, SD) 46.1 ± 11.9 years, had a mean BMI of 25.6 ± 4.88 kg/m2 and were predominantly female (73%). 95% of participants were snackers (≥ 1 snack/day; n = 813); mean daily snack intake was 2.28 snacks/day (24 ± 16% of daily calories; 203 ± 170 kcal); and 44% of participants were discordant for meal and snack quality. In snackers, overall snacking frequency and quantity of snack energy were not associated with cardiometabolic risk markers. However, lower snack quality (SDI range 1-11) was associated with higher blood markers, including elevated fasting triglycerides (TG (mmol/L) ß; - 0.02, P = 0.02), postprandial TGs (6hiAUC (mmol/L.s); ß; - 400, P = 0.01), fasting insulin (mIU/L) (ß; - 0.15, P = 0.04), insulin resistance (HOMA-IR; ß; - 0.04, P = 0.04) and hunger (scale 0-100) (ß; - 0.52, P = 0.02) (P values non-significant after multiple testing adjustments). Late-evening snacking (≥ 9 pm; 31%) was associated with lower blood markers (HbA1c; 5.54 ± 0.42% vs 5.46 ± 0.28%, glucose 2hiAUC; 8212 ± 5559 vs 7321 ± 4928 mmol/L.s, P = 0.01 and TG 6hiAUC; 11,638 ± 8166 vs 9781 ± 6997 mmol/L.s, P = 0.01) compared to all other snacking times (HbA1c remained significant after multiple testing). CONCLUSION: Snack quality and timing of consumption are simple diet features which may be targeted to improve diet quality, with potential health benefits. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: NCT03479866, https://clinicaltrials.gov/ct2/show/NCT03479866?term=NCT03479866&draw=2&rank=1.

Glycaemic variability, assessed with continuous glucose monitors, is associated with diet, lifestyle and health in people without diabetes.

Background: Continuous glucose monitors (CGMs) provide high-frequency information regarding daily glucose variation and are recognised as effective for improving glycaemic control in individuals living with diabetes. Despite increased use in individuals with non-diabetic blood glucose concentrations (euglycemia), their utility as a health tool in this population remains unclear. Objectives: To characterise variation in time in range (TIR) and glycaemic variability in large populations without diabetes or impaired glucose tolerance; describe associations between CGM-derived glycaemic metrics and metabolic and cardiometabolic health traits; identify key diet and lifestyle factors associated with TIR and glycaemic variability. Design: Glycaemic variability (coefficient of variation) and time spent in both the ADA secondary target range (TIRADA; 3.9-7.8 mmol/L) and a more stringent range (TIR3.9-5.6; 3.9-5.6 mmol/L) were calculated during free-living in PREDICT 1, PREDICT 2, and PREDICT 3 euglycaemic community-based volunteer cohorts. Associations between CGM derived glycaemic metrics, markers of cardiometabolic health, diet (food frequency questionnaire and logged diet records), diet-habits, and lifestyle were explored. Results: Data from N=4135 participants (Mean SD; Age: 47 12 y; Sex: 83% Female, BMI: 27 6 kg/m2). Median glycaemic variability was 14.8% (IQR 12.6-17.6%), median TIRADA was 95.8% (IQR 89.6-98.6%) and TIR3.9-5.6 was 75.0% (IQR 64.6-82.8%). Greater TIR3.9-5.6 was associated with lower HbA1c, ASCVD 10y risk and HOMA-IR (all p < 0.05). Lower glycaemic variability was associated with lower % energy derived from carbohydrate (rs: 0.17, p < 0.01), ultra-processed foods (NOVA 4, % EI; rs: 0.12, p = 0.01) and a longer overnight fasting duration (rs: -0.10, p = 0.01). Conclusions: A stringent TIR target provides sensitivity to detect changes in HOMA-IR, ASCVD 10 y risk and HbA1c that were not detected using ADA secondary targets. Associations among TIR, glycaemic variability, dietary intake (e.g. carbohydrate and protein) and habits (e.g. nocturnal fasting duration) highlight potential strategic targets to improve glycaemic metrics derived from continuous glucose monitors.

Mechanisms of interesterified fat digestibility in a muffin matrix using a dynamic gastric model.

Industrially generated trans-fats have been linked with cardiovascular disease (CVD) and have thus been replaced by interesterified (IE) fats, in foods. Interesterification rearranges fatty acids on the glycerol backbone of a triacylglycerol molecule. However, the impact of IE fat on health is unknown. We recently reported differences in lipid absorption kinetics between IE and rapeseed oil (RO). Here, we investigated the mechanisms underpinning IE fat digestion kinetics in the same muffins baked using an IE fat, non-IE fat [with the same fatty acid composition] and rapeseed oil (RO) under simulated conditions. IE and non-IE fats were largely solid in the gastric phase and strongly associated within the muffin matrix, whereas RO formed liquid droplets which separated from the matrix. No significant difference in lipolysis rates was detected between IE and non-IE fats. The lipolysis of the RO fat was slower, due to long-chain PUFAs. Interesterification itself did not affect digestibility, but the strong interaction between the hard fats and the muffin matrix resulted in extensive creaming of the matrix in the stomach, leading to delayed gastric emptying compared to the RO sample. The rate and extent of lipolysis were determined by the amount of fat available and the structure of the fat. This demonstrates the importance of the physical behaviour of the fats during digestion and provides a mechanistic understanding of the overall lipid digestion of IE fats, which relates to their physiological response.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions.

The Segatella copri (formerly Prevotella copri) complex (ScC) comprises taxa that are key members of the human gut microbiome. It was previously described to contain four distinct phylogenetic clades. Combining targeted isolation with large-scale metagenomic analysis, we defined 13 distinct Segatella copri-related species, expanding the ScC complex beyond four clades. Complete genome reconstruction of thirteen strains from seven species unveiled the presence of genetically diverse large circular extrachromosomal elements. These elements are consistently present in most ScC species, contributing to intra- and inter-species diversities. The nine species-level clades present in humans display striking differences in prevalence and intra-species genetic makeup across human populations. Based on a meta-analysis, we found reproducible associations between members of ScC and the male sex and positive correlations with lower visceral fat and favorable markers of cardiometabolic health. Our work uncovers genomic diversity within ScC, facilitating a better characterization of the human microbiome.

Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.

BACKGROUND: B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants. RESULTS: Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites - pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) - were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E-09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals. CONCLUSION: Metabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.

Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort.

PURPOSE: In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). METHODS: We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. RESULTS: The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen's effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. CONCLUSIONS: Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h2: serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.

Plasma protein N-glycome composition associates with postprandial lipaemic response.

BACKGROUND: A dysregulated postprandial metabolic response is a risk factor for chronic diseases, including type 2 diabetes mellitus (T2DM). The plasma protein N-glycome is implicated in both lipid metabolism and T2DM risk. Hence, we first investigate the relationship between the N-glycome and postprandial metabolism and then explore the mediatory role of the plasma N-glycome in the relationship between postprandial lipaemia and T2DM. METHODS: We included 995 individuals from the ZOE-PREDICT 1 study with plasma N-glycans measured by ultra-performance liquid chromatography at fasting and triglyceride, insulin, and glucose levels measured at fasting and following a mixed-meal challenge. Linear mixed models were used to investigate the associations between plasma protein N-glycosylation and metabolic response (fasting, postprandial (Cmax), or change from fasting). A mediation analysis was used to further explore the relationship of the N-glycome in the prediabetes (HbA1c = 39-47 mmol/mol (5.7-6.5%))-postprandial lipaemia association. RESULTS: We identified 36 out of 55 glycans significantly associated with postprandial triglycerides (Cmax ß ranging from -0.28 for low-branched glycans to 0.30 for GP26) after adjusting for covariates and multiple testing (padjusted < 0.05). N-glycome composition explained 12.6% of the variance in postprandial triglycerides not already explained by traditional risk factors. Twenty-seven glycans were also associated with postprandial glucose and 12 with postprandial insulin. Additionally, 3 of the postprandial triglyceride-associated glycans (GP9, GP11, and GP32) also correlate with prediabetes and partially mediate the relationship between prediabetes and postprandial triglycerides. CONCLUSIONS: This study provides a comprehensive overview of the interconnections between plasma protein N-glycosylation and postprandial responses, demonstrating the incremental predictive benefit of N-glycans. We also suggest a considerable proportion of the effect of prediabetes on postprandial triglycerides is mediated by some plasma N-glycans.

Characterisation of Fasting and Postprandial NMR Metabolites: Insights from the ZOE PREDICT 1 Study.

BACKGROUND: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort. METHODS: In the ZOE PREDICT 1 study (n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated. RESULTS: Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (ß-hydroxybutyrate, acetoacetate, acetate) and lactate. CONCLUSIONS: In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.

The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery.

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (ß = -0.72, p = 1 × 10-5) and in response to fiber supplementation (ß = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.

Cardiometabolic health, diet and the gut microbiome: a meta-omics perspective.

Cardiometabolic diseases have become a leading cause of morbidity and mortality globally. They have been tightly linked to microbiome taxonomic and functional composition, with diet possibly mediating some of the associations described. Both the microbiome and diet are modifiable, which opens the way for novel therapeutic strategies. High-throughput omics techniques applied on microbiome samples (meta-omics) hold the unprecedented potential to shed light on the intricate links between diet, the microbiome, the metabolome and cardiometabolic health, with a top-down approach. However, effective integration of complementary meta-omic techniques is an open challenge and their application on large cohorts is still limited. Here we review meta-omics techniques and discuss their potential in this context, highlighting recent large-scale efforts and the novel insights they provided. Finally, we look to the next decade of meta-omics research and discuss various translational and clinical pathways to improving cardiometabolic health.

Particle Size Distribution and Predicted Lipid Bioaccessibility of Almonds and the Effect of Almond Processing: A Randomised Mastication Study in Healthy Adults.

Almonds are rich in unsaturated lipids, which play a role in some of the reported benefits of almond consumption for human health. Almond lipids are poorly bioaccessible due to almonds' unique physicochemical properties that influence particle size distribution (PSD) following mastication, allowing much intracellular lipid to escape digestion in the upper gastrointestinal tract. To investigate the impact of commercial processing (grinding almonds into flour), on PSD and predicted lipid bioaccessibility following mastication, a randomised cross-over design mastication study was conducted in healthy adults. The PSDs of masticated whole and ground almonds was assessed using two laboratory methods (mechanical sieving and laser diffraction). PSD from mechanical sieving was used to calculate lipid bioaccessibility using a theoretical mathematical model. Thirty-one healthy adults (18-45 years) completed both mastication sessions. Following mastication, ground almonds had a PSD with significantly fewer larger particles and more smaller particles, compared with whole almonds. Predicted lipid bioaccessibility of masticated ground almonds (10.4%, SD 1.8) was marginally but significantly greater than the predicted lipid bioaccessibility of masticated whole almonds (9.3%, SD 2.0; p = 0.017). Commercial grinding of almonds significantly influences the PSD of almonds following mastication, which results in a modest but significant increase in predicted lipid bioaccessibility.

Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4.

Metagenomic assembly enables new organism discovery from microbial communities, but it can only capture few abundant organisms from most metagenomes. Here we present MetaPhlAn 4, which integrates information from metagenome assemblies and microbial isolate genomes for more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01 M prokaryotic reference and metagenome-assembled genomes, we define unique marker genes for 26,970 species-level genome bins, 4,992 of them taxonomically unidentified at the species level. MetaPhlAn 4 explains ~20% more reads in most international human gut microbiomes and >40% in less-characterized environments such as the rumen microbiome and proves more accurate than available alternatives on synthetic evaluations while also reliably quantifying organisms with no cultured isolates. Application of the method to >24,500 metagenomes highlights previously undetected species to be strong biomarkers for host conditions and lifestyles in human and mouse microbiomes and shows that even previously uncharacterized species can be genetically profiled at the resolution of single microbial strains.

Enhanced secretion of satiety-promoting gut hormones in healthy humans after consumption of white bread enriched with cellular chickpea flour: A randomized crossover study.

BACKGROUND: Dietary intake of pulses is associated with beneficial effects on body weight management and cardiometabolic health, but some of these effects are now known to depend on integrity of plant cells, which are usually disrupted by flour milling. Novel cellular flours preserve the intrinsic dietary fiber structure of whole pulses and provide a way to enrich preprocessed foods with encapsulated macronutrients. OBJECTIVES: This study aimed to determine the effects of replacing wheat flour with cellular chickpea flour on postprandial gut hormones, glucose, insulin, and satiety responses to white bread. METHODS: We conducted a double-blind randomized crossover study in which postprandial blood samples and scores were collected from healthy human participants (n = 20) after they consumed bread enriched with 0%, 30%, or 60% (wt/wt) cellular chickpea powder (CCP, 50 g total starch per serving). RESULTS: Bread type significantly affected postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) responses (time × treatment, P = 0.001 for both). The 60% CCP breads elicited significantly elevated and sustained release of these anorexigenic hormones [between 0% and 60% CPP-GLP-1: mean difference incremental area under the curve (iAUC), 3101 pM/min; 95% CI: 1891, 4310; P-adjusted < 0.001; PYY: mean difference iAUC, 3576 pM/min; 95% CI: 1024, 6128; P-adjusted = 0.006] and tended to increase fullness (time × treatment, P = 0.053). Moreover, bread type significantly influenced glycemia and insulinemia (time × treatment, P < 0.001, P = 0.006, and P = 0.001 for glucose, insulin, and C-peptide, respectively), with 30% CCP breads eliciting a >40% lower glucose iAUC (P-adjusted < 0.001) than the 0% CCP bread. Our in vitro studies revealed slow digestion of intact chickpea cells and provide a mechanistic explanation for the physiologic effects. CONCLUSIONS: The novel use of intact chickpea cells to replace refined flours in a white bread stimulates an anorexigenic gut hormone response and has potential to improve dietary strategies for prevention and treatment of cardiometabolic diseases. This study was registered at clinicaltrials.gov as NCT03994276.

How people wake up is associated with previous night's sleep together with physical activity and food intake.

How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual's set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable.

Postprandial Responses to a Standardised Meal in Hypertension: The Mediatory Role of Visceral Fat Mass.

Postprandial insulinaemia, triglyceridaemia and measures of inflammation are thought to be more closely associated with cardiovascular risk than fasting measures. Although hypertension is associated with altered fasting metabolism, it is unknown as to what extent postprandial lipaemic and inflammatory metabolic responses differ between hypertensive and normotensive individuals. Linear models adjusting for age, sex, body mass index (BMI), visceral fat mass (VFM) and multiple testing (false discovery rate), were used to investigate whether hypertensive cases and normotensive controls had different fasting and postprandial (in response to two standardised test meal challenges) lipaemic, glycaemic, insulinaemic, and inflammatory (glycoprotein acetylation (GlycA)) responses in 989 participants from the ZOE PREDICT-1 nutritional intervention study. Compared to normotensive controls, hypertensive individuals had significantly higher fasting and postprandial insulin, triglycerides, and markers of inflammation after adjusting for age, sex, and BMI (effect size: Beta (Standard Error) ranging from 0.17 (0.08), p = 0.04 for peak insulin to 0.29 (0.08), p = 4.4 × 10-4 for peak GlycA). No difference was seen for postprandial glucose. When further adjusting for VFM effects were attenuated. Causal mediation analysis suggests that 36% of the variance in postprandial insulin response and 33.8% of variance in postprandial triglyceride response were mediated by VFM. Hypertensive individuals have different postprandial insulinaemic and lipaemic responses compared to normotensive controls and this is partially mediated by visceral fat mass. Consequently, reducing VFM should be a key focus of health interventions in hypertension. Trial registration: The ClinicalTrials.gov registration identifier is NCT03479866.

Reproducibility of sequential ambulatory blood pressure and pulse wave velocity measurements in normotensive and hypertensive individuals.

OBJECTIVE: Errors in blood pressure (BP) measurement account for a large proportion of misclassified hypertension diagnoses. Ambulatory blood pressure monitoring (ABPM) is often considered to be the gold standard for measurement of BP, but uncertainty remains regarding the degree of measurement error. The aim of this study was to determine reproducibility of sequential ABPM in a population of normotensive and well controlled hypertensive individuals. METHODS: Individual participant data from three randomized controlled trials, which had recorded ABPM and carotid-femoral pulse wave velocity (PWV) at least twice were combined ( n  = 501). We calculated within-individual variability of daytime and night-time BP and compared the variability between normotensive ( n  = 324) and hypertensive ( n  = 177) individuals. As a secondary analysis, variability of PWV measurements was also calculated, and multivariable linear regression was used to assess characteristics associated with blood pressure variability (BPV). RESULTS: Within-individual coefficient of variation (CoV) for systolic BP was 5.4% (day) and 7.0% (night). Equivalent values for diastolic BP were 6.1% and 8.4%, respectively. No statistically significant difference in CoV was demonstrated between measurements for normotensive and hypertensive individuals. Within-individual CoV for PWV exceeded that of BP measurements (10.7%). BPV was associated with mean pressures, and BMI for night-time measurements. PWV was not independently associated with BPV. CONCLUSION: The variability of single ABPM measurements will still yield considerable uncertainty regarding true average pressures, potentially resulting in misclassification of hypertensive status and incorrect treatment regimes. Repeated ABPM may be necessary to refine antihypertensive therapy.