To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals ...Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.
Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the ...Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial.
In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples.
Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction.
Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors.
The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.
The effect of microbes on their human host is often mediated through changes in metabolite concentrations. As such, multiple tools have been proposed to predict metabolite concentrations from ...microbial taxa frequencies. Such tools typically fail to capture the dependence of the microbiome-metabolite relation on the environment.
We propose to treat the microbiome-metabolome relation as the equilibrium of a complex interaction and to relate the host condition to a latent representation of the interaction between the log concentration of the metabolome and the log frequencies of the microbiome. We develop LOCATE (Latent variables Of miCrobiome And meTabolites rElations), a machine learning tool to predict the metabolite concentration from the microbiome composition and produce a latent representation of the interaction. This representation is then used to predict the host condition. LOCATE's accuracy in predicting the metabolome is higher than all current predictors. The metabolite concentration prediction accuracy significantly decreases cross datasets, and cross conditions, especially in 16S data. LOCATE's latent representation predicts the host condition better than either the microbiome or the metabolome. This representation is strongly correlated with host demographics. A significant improvement in accuracy (0.793 vs. 0.724 average accuracy) is obtained even with a small number of metabolite samples (Formula: see text).
These results suggest that a latent representation of the microbiome-metabolome interaction leads to a better association with the host condition than any of the two separated or the simple combination of the two. Video Abstract.
Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging ...in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention.
In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age.
To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age.
Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging.
The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai).
•We examined neural correlates of weight loss following a lifestyle intervention.•Weight loss correlated with baseline connectivity within a functional subnetwork.•The weight loss subnetwork is ...comprised of senso-motor cortical regions.•We tested a novel hypothesis regarding the role of brain-gastric interaction.
Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.
Background Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary ...polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m.sup.2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). Conclusions A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. Trial registration ClinicalTrials.gov, NCT03020186 Keywords: Mediterranean, Obesity, Plant-based diet, Polyphenols, Visceral adipose tissue
Background and Aims
In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual ...variation. Moreover, genetic factors are involved in developing nonalcoholic fatty‐liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA‐methylation of NAFLD related genes associated with IHF.
Methods
For 120 participants from the CENTRAL trial, an 18‐month regimen of either low‐fat (LF) or Mediterranean‐low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA−), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA‐methylation levels of 41 selected candidate genes. Single‐nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays.
Results
At baseline, participants (92% men; body mass index = 30.2 kg/m2) had mean IHF of 10.7% (59% NAFLD). Baseline‐IHF% was inversely correlated with DNA‐methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18‐month lifestyle intervention, differential DNA‐methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA‐methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA−vs. PA+).
Conclusions
This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long‐term lifestyle interventions.
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•Wolffia globosa an emerging functional food, targets obesity and metabolic disease.•Wolffia globosa rich in fiber and polyphenols modulates the gut microbiome.•Wolffia globosa ...increases microbiota phenolic acid and SCFA production in vitro.•Microbiome modulation may underpin certain health effects of Wolffia globosa ingestion.
Mankai® is a cultivated strain of Wolffia globosa an aquatic plant of the family Lemnaceae commonly known as Duckweeds. Recent studies suggest that consumption of a Mankai® enriched diet may provide positive health effects by decreasing body weight and improving glucose homeostasis and plasma lipid profiles. However, the effects of Mankai® alone on the composition and metabolic output of the human gut microbiota has not been fully investigated. Here, Mankai® was digested and fermented in vitro using a batch culture model of the proximal colon. Inulin and cellulose were used as readily and poorly fermentable control fibers respectively. Mankai® significantly stimulated the production of phenolic metabolites and short chain fatty acids by the gut microbiota (p<0.05). Three major microbial metabolites, 3-4-hydroxyphenyl propionic acid, 3-3-hydroxyphenyl propanoic acid and protocatechuic acid were significantly increased after 24 h fermentation. Moreover, Mankai® treatment lowered the overall microbial diversity (p<0.05), in line with a selective microbiome modulation.
Background: Rare plants that contain corrinoid compounds mostly comprise cobalamin analogues, which may compete with cobalamin (vitamin B12 (B12)) metabolism. We examined the presence of B12 in a ...cultivated strain of an aquatic plant: Wolffia globosa (Mankai), and predicted functional pathways using gut-bioreactor, and the effects of long-term Mankai consumption as a partial meat substitute, on serum B12 concentrations. Methods: We used microbiological assay, liquid-chromatography/electrospray-ionization-tandem-mass-spectrometry (LC-MS/MS), and anoxic bioreactors for the B12 experiments. We explored the effect of a green Mediterranean/low-meat diet, containing 100 g of frozen Mankai shake/day, on serum B12 levels during the 18-month DIRECT-PLUS (ID:NCT03020186) weight-loss trial, compared with control and Mediterranean diet groups. Results: The B12 content of Mankai was consistent at different seasons (p = 0.76). Several cobalamin congeners (Hydroxocobalamin(OH-B12); 5-deoxyadenosylcobalamin(Ado-B12); methylcobalamin(Me-B12); cyanocobalamin(CN-B12)) were identified in Mankai extracts, whereas no pseudo B12 was detected. A higher abundance of 16S-rRNA gene amplicon sequences associated with a genome containing a KEGG ortholog involved in microbial B12 metabolism were observed, compared with control bioreactors that lacked Mankai. Following the DIRECT-PLUS intervention (n = 294 participants; retention-rate = 89%; baseline B12 = 420.5 ± 187.8 pg/mL), serum B12 increased by 5.2% in control, 9.9% in Mediterranean, and 15.4% in Mankai-containing green Mediterranean/low-meat diets (p = 0.025 between extreme groups). Conclusions: Mankai plant contains bioactive B12 compounds and could serve as a B12 plant-based food source.
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