Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women

Omega-3 fatty acids may influence human physiological parameters in part by affecting the gut microbiome. The aim of this study was to investigate the links between omega-3 fatty acids, gut microbiome diversity and composition and faecal metabolomic profiles in middle aged and elderly women. We analysed data from 876 twins with 16S microbiome data and DHA, total omega-3, and other circulating fatty acids. Estimated food intake of omega-3 fatty acids were obtained from food frequency questionnaires. Both total omega-3and DHA serum levels were significantly correlated with microbiome alpha diversity (Shannon index) after adjusting for confounders (DHA Beta(SE) = 0.13(0.04), P = 0.0006 total omega-3: 0.13(0.04), P = 0.001). These associations remained significant after adjusting for dietary fibre intake. We found even stronger associations between DHA and 38 operational taxonomic units (OTUs), the strongest ones being with OTUs from the Lachnospiraceae family (Beta(SE) = 0.13(0.03), P = 8 × 10-7). Some of the associations with gut bacterial OTUs appear to be mediated by the abundance of the faecal metabolite N-carbamylglutamate. Our data indicate a link between omega-3 circulating levels/intake and microbiome composition independent of dietary fibre intake, particularly with bacteria of the Lachnospiraceae family. These data suggest the potential use of omega-3 supplementation to improve the microbiome composition

Metabolomic Profiling of Long-Term Weight Change:Role of Oxidative Stress and Urate Levels in Weight Gain

OBJECTIVE: To investigate the association between long-term weight change and blood metabolites. METHODS: Change in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3-79.6, baseline BMI: 25.11 ± 4.35) measured for 280 metabolites at follow-up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n = 1,760; age range: 25-70, baseline BMI: 27.72 ± 4.53). The study examined whether the metabolites identified could prospectively predict weight change in KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n = 471; age range: 55-74, baseline BMI: 27.24 ± 5.37). RESULTS: Thirty metabolites were significantly associated with change in BMI per year in TwinsUK using Bonferroni correction. Four were independently associated with weight change in the multivariable LASSO model and replicated in KORA: namely, urate (meta-analysis β [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 × 10-19 ), gamma-glutamyl valine (β [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 × 10-20 ), butyrylcarnitine (β [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 × 10-12 ), and 3-phenylpropionate (β [95% CI] = -0.03 [-0.041 to -0.019]; P = 9.8 × 10-8 ), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO. CONCLUSIONS: Metabolites linked to higher oxidative stress are associated with increased long-term weight gain

Heritable components of the human fecal microbiome are associated with visceral fat

Background: Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.Results: We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.Conclusions: Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies

Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: a twin study

Background: Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics.  Methods: In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, highsensitivity C-reactive protein (hs-CRP) and lipids. We also measured plasma concentrations of BCAA and known metabolites of amino acid metabolism using untargeted mass spectrometry. Using a within-twin design, multivariable analyses were used to compare the associations between BCAA intake and endpoints of cardiometabolic health, independently of genetic confounding.  Results: Higher BCAA intake was significantly associated with lower HOMA-IR (-0.1, Ptrend 0.02), insulin (-0.5 µU/mL, P-trend 0.03), hs-CRP -0.3 mg/L, P-trend 0.01), systolic blood pressure (-2.3 mm Hg, P-trend 0.01) and waist-to-height ratio (-0.01, P-trend 0.04), comparing extreme quintiles of intake. These associations persisted in within-pair analysis for monozygotic twins for insulin resistance (P<0.01), inflammation (P=0.03), and blood pressure (P=0.04) suggesting independence from genetic confounding. There were no association between BCAA intake and plasma concentrations, although two metabolitespreviously associated with obesity were inversely associated with BCAA intake (alphahydroxyisovalerate and trans-4-hydroxyproline).  Conclusions: Higher intakes of BCAA were associated, independently of genetics, with lower insulin resistance, inflammation, blood pressure and adiposity-related metabolites. The BCAA intake associated with our findings are easily achievable in the habitual diet.  Abbreviations: BCAA, branched chain amino acids; DBP, diastolic blood pressure; DZ, dizygotic; FFQ, food frequency questionnaire; HDL-C, high density lipoprotein cholesterol; hs-CRP, high sensitivity C-reactive protein; MZ, monozygotic; SBP, systolic blood pressure; T2DM, type 2 diabetes; SBP, systolic blood pressure; WHtR, waist to height rati

A Historicai Consideration on the Changes of the Wabicha (Tea Ceremony) and the Roji (Tea Garden) : Part 3: The Succession and development of Oribe\u27s Style for Tea Ceremony by Enshu

織部において, 茶室, 茶庭は客のためのよりよき茶を演出するための場としてとらえる立場をとる.この織部の茶を継承し, さらに展開した遠州は茶庭(露地)のための造形を含めて, かずかずの茶の造形をものしている.しかも, その中には, 後世に受けつがれ, 語りつがれる, すぐれた数々の成果がある.このすぐれた成果を生み出した基盤には, 彼の豊かな天賦の才があったこと勿論であるが, しかし, 一方, 彼を取り巻くすぐれた人びとが, 彼のこのすぐれた天賦の才をさらにみがき, そして大きく育てる役割を果したことも, また軽視できないといわねばならない.本報告では, このような遠州を取り巻くすぐれた人びとの中で, 特に松花堂昭乗を取りあげる.滝本坊客殿の幅広い東縁と, これから茶室・閑雲軒の躙口へ通じる狭い榑縁と, このひとつらなりの廊下がつくり出す構成は, 外露地から内露地への園路の構成に通じるものといえる.而して, この構成を, 遠州が先きに金地院八窓席の躙口まえにおいて試みた手法から, さらに一歩を踏み出したデザインとみる.また, その手水構えにおいても, ここ閑雲軒においては, 蹲踞構えではなく, 書院における縁先手水の構えを思わせる構成をとるものであって, それは廊下を園路と見立てる手法によって, はじめて成立する構成といえる.そして, この構成は, やがて, 書院茶室へと展開する遠州の新しい茶の造形に向う, 一階梯として大きな意義をもつ.また, 滝本坊茶立所の室内構成をみるとき, そこには遠州伏見屋敷におけるデザインからの発展といえるかずかずの特徴がみられる.さらに, この滝本坊茶立所における作事のかずかずの体験が, やがて, 遠州の造形デザインの世界を, さEnshu Kobori succeeded Oribe Furuta\u27s style for a wabicha (a tea ceremony in the special room or house for it) to recieve the quests with a tea in the hospitable settings of a room and a garden, and developed it cultivating his talent by the communicaion with several outstanding people of his salon like Shojo Shokado or a monk of Iwashimizu Hachimangu. One of the process of the development could be found in the approach from the kyakuden (a reception hall) of Takimotobo of Shojo\u27s living house to Kanunken of a special house for a tea ceremony through the verandah, and in the design of chatatedokoro, i.e. the room for a wabicha in a shoin style. The way from the kyakuden to Kanunken through the verandah would have been supposed as the way from a soto-roji to a uchi-roji, and a set of tsukubai or a basin for washing hands beside the verandah used like a ensaki-chouzu in case of a shoincha or a tea service in a shoin. And, we can point out several effects of Shojo in the design of chatatedokoro. Therefore, the design of Takimotobo is on the way to a wabicha in a shoin style, which is completed by Enshu in the design of Bosen of Kohoan, Daitokuji

Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts

Purpose: Milk provides a significant source of calcium, protein, vitamins and other minerals to Western populations throughout life. Due to its widespread use, the metabolic and health impact of milk consumption warrants further investigation and biomarkers would aid epidemiological studies.  Methods: Milk intake assessed by a validated food frequency questionnaire was analyzed against fasting blood metabolomic profiles from two metabolomic platforms in females from the TwinsUK cohort (n = 3559). The top metabolites were then replicated in two independent populations (EGCUT, n = 1109 and KORA, n = 1593), and the results from all cohorts were meta-analyzed.  Results: Four metabolites were significantly associated with milk intake in the TwinsUK cohort after adjustment for multiple testing (P < 8.08 × 10−5) and covariates (BMI, age, batch effects, family relatedness and dietary covariates) and replicated in the independent cohorts. Among the metabolites identified, the carnitine metabolite trimethyl-N-aminovalerate (β = 0.012, SE = 0.002, P = 2.98 × 10−12) and the nucleotide uridine (β = 0.004, SE = 0.001, P = 9.86 × 10−6) were the strongest novel predictive biomarkers from the non-targeted platform. Notably, the association between trimethyl-N-aminovalerate and milk intake was significant in a group of MZ twins discordant for milk intake (β = 0.050, SE = 0.015, P = 7.53 × 10−4) and validated in the urine of 236 UK twins (β = 0.091, SE = 0.032, P = 0.004). Two metabolites from the targeted platform, hydroxysphingomyelin C14:1 (β = 0.034, SE = 0.005, P = 9.75 × 10−14) and diacylphosphatidylcholine C28:1 (β = 0.034, SE = 0.004, P = 4.53 × 10−16), were also replicated.  Conclusions: We identified and replicated in independent populations four novel biomarkers of milk intake: trimethyl-N-aminovalerate, uridine, hydroxysphingomyelin C14:1 and diacylphosphatidylcholine C28:1. Together, these metabolites have potential to objectively examine and refine milk-disease associations

Characterizing blood metabolomics profiles associated with self-reported food intakes in female twins

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations