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Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Faecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 region). General linear models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: β=−0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.
Urinary O-desmethylangolensin (ODMA) concentrations provide a functional gut microbiome marker of dietary isoflavone daidzein metabolism to ODMA. Individuals who do not have gut microbial environments that produce ODMA have less favourable cardiometabolic and cancer risk profiles. Urinary metabolomics profiles were evaluated in relation to ODMA metabotypes within and between individuals over time. Secondary analysis of data was conducted from the BEAN2 trial, which was a cross-over study of premenopausal women consuming 6 months on a high and a low soya diet, each separated by a 1-month washout period. In all of the 672 samples in the study, sixty-six of the eighty-four women had the same ODMA metabotype at seven or all eight time points. Two or four urine samples per woman were selected based on temporal metabotypes in order to compare within and across individuals. Metabolomics assays for primary metabolism and biogenic amines were conducted in sixty urine samples from twenty women. Partial least-squares discriminant analysis was used to compare metabolomics profiles. For the same ODMA metabotype across different time points, no profile differences were detected. For changes in metabotype within individuals and across individuals with different metabotypes, distinct metabolomes emerged. Influential metabolites (variables importance in projection score > 2) included several phenolic compounds, carnitine and derivatives, fatty acid and amino acid metabolites and some medications. Based on the distinct metabolomes of producers v. non-producers, the ODMA metabotype may be a marker of gut microbiome functionality broadly involved in nutrient and bioactive metabolism and should be evaluated for relevance to precision nutrition initiatives.
As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993–1996), 5280 at follow-up (Q3, 2003–2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013–2016). All participants provided a stool sample in 2013–2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.
Dietary indices have been related to risk for type 2 diabetes (T2D) predominantly in white populations. The present study evaluated this association in the ethnically diverse Multiethnic Cohort and examined four diet quality indices in relation to T2D risk, homoeostatic model assessment-estimated insulin resistance (HOMA-IR) and biomarkers of dyslipidaemia, inflammation and adipokines. The T2D analysis included 166 550 white, African American, Native Hawaiian, Japanese American and Latino participants (9200 incident T2D cases). Dietary intake was assessed at baseline using a quantitative FFQ and T2D status was based on three self-reports and confirmed by administrative data. Biomarkers were assessed about 10 years later in a biomarker subcohort (n 10 060). Sex- and ethnicity-specific hazard ratios were calculated for the Healthy Eating Index-2010 (HEI-2010), the alternative HEI-2010 (AHEI-2010), the alternate Mediterranean diet score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). Multivariable-adjusted means of biomarkers were compared across dietary index tertiles in the biomarker subcohort. The AHEI-2010, aMED (in men only) and DASH scores were related to a 10–20 % lower T2D risk, with the strongest associations in whites and the direction of the relationships mostly consistent across ethnic groups. Higher scores on the four indices were related to lower HOMA-IR, TAG and C-reactive protein concentrations, not related to leptin, and the DASH score was directly associated with adiponectin. The AHEI-2010 and DASH were directly related to HDL-cholesterol in women. Potential underlying biological mechanisms linking diet quality and T2D risk are an improved lipid profile and reduced systemic inflammation and, with regards to DASH alone, an improved adiponectin profile.
For cancer prevention, the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) emphasise recommendations to improve individual behaviour, including avoidance of tobacco products, maintaining a lean body mass, participating in physical activity, consuming a plant-based diet, and minimising the consumption of energy-dense foods, such as sodas, red and processed meats and alcohol. In the present study of 275 healthy premenopausal women, we explored the association of adherence scores with levels of three biomarkers of antioxidant and inflammation status: serum C-reactive protein (CRP), serum γ-tocopherol and urinary F2-isoprostane. The statistical analysis applied linear regression across categories of adherence to WCRF/AICR recommendations. Overall, seventy-two women were classified as low ( ≤ 4), 150 as moderate (5–6), and fifty-three as high adherers ( ≥ 7). The unadjusted means for CRP were 2·7, 2·0 and 1·7 mg/l for low, moderate and high adherers (Ptrend= 0·03); this association was strengthened after adjustment for confounders (Ptrend= 0·006). The respective values for serum γ-tocopherol were 1·97, 1·63 and 1·45 μg/ml (Ptrend= 0·02 before and Ptrend= 0·03 after adjustment). Only for urinary F2-isoprostane, the lower values in high adherers (16·0, 14·5, and 13·3 ng/ml) did not reach statistical significance (Ptrend= 0·18). In an analysis by BMI, overweight and obese women had higher biomarker levels than normal weight women; the trend was significant for CRP (Ptrend< 0·001) and γ-tocopherol (Ptrend= 0·003) but not for F2-isoprostane (Ptrend= 0·14). These findings suggest that both adherence to the WCRF/AICR guidelines and normal BMI status are associated with lower levels of biomarkers that indicate oxidative stress and inflammation.
Given the high intake levels of soya and low incidence rates of breast cancer in Asian countries, isoflavones, substances with an oestrogen-like structure occurring principally in soyabeans, are postulated to be cancer protective. In the present study, we examined the association of dietary isoflavone intake with breast cancer risk in 84 450 women (896 in situ and 3873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans and Native Hawaiians) with a wide range of soya intake levels. The absolute levels of dietary isoflavone intake estimated from a baseline FFQ were categorised into quartiles, with the highest quartile being further subdivided to assess high dietary intake. The respective intake values for the quartiles (Q1, Q2, Q3, and lower and upper Q4) were 0– < 3·2, 3·2– < 6·7, 6·7– < 12·9, 12·9– < 20·3, and 20·3–178·7 mg/d. After a mean follow-up period of 13 years, hazard ratios (HR) and 95 % CI were calculated using Cox regression models stratified by age and adjusted for known confounders. Linear trends were tested by modelling continuous variables of interest assigned the median value within the corresponding quartile. No statistically significant association was observed between dietary isoflavone intake and overall breast cancer risk (HR for upper Q4 v. Q1: 0·96 (95 % CI 0·85, 1·08); P trend = 0·40). While the test for interaction was not significant (P= 0·14), stratified analyses suggested possible ethnic/racial differences in risk estimates, indicating that higher isoflavone intakes may be protective in Latina, African American and Japanese American women. These results are in agreement with those of previous meta-analyses showing no protection of isoflavones at low intake levels, but suggesting inverse associations in populations consuming high amounts of soya.
Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status.
Intervention with repeated measures.
Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women.
BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E1) and oestradiol (E2) using RIA. Nine oestrogen metabolites were measured in urine by LC–MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders.
The mean age of the 272 participants was 41·9 (sd 4·5) years. Serum E1 (85 v. 100 pg/ml, P = 0·04) and E2 (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations.
Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.
We evaluated the influence of coffee consumption on diabetes incidence among the Hawaii component of the Multiethnic Cohort (MEC).
Population-based sample residing in Hawaii.
After exclusions, 75 140 men and women of Caucasian, Japanese American and Native Hawaiian ancestry aged 45–75 years were part of the current analysis. All participants provided information on diet and lifestyle through an FFQ. After 14 years of follow-up 8582 incident diabetes cases were identified using self-reports, medication questionnaires and health plan linkages. Hazard ratios (HR) and 95 % confidence intervals were calculated using Cox regression while adjusting for known covariates.
The risk for diabetes associated with total coffee consumption differed by sex (Pinteraction < 0·0001). Women consuming ≥3 cups of any type of coffee daily had a significantly lower risk (HR = 0·66; 95 % CI 0·58, 0·77; Ptrend < 0·0001) than those reporting <1 cup/d, whereas the relationship in men was borderline (HR = 0·89; 95 % CI 0·80, 0·99; Ptrend = 0·09). The same difference by sex was seen for regular coffee consumption, with HR of 0·65 (95 % CI 0·54, 0·78; Ptrend < 0·0001) and 0·86 (95 % CI 0·75, 0·98; Ptrend = 0·09) in men and women, respectively. No significant association with diabetes was apparent for decaffeinated coffee in women (HR = 0·85; 95 % CI 0·72, 1·01; Ptrend = 0·73) or men (HR = 1·07; 95 % CI 0·93, 1·23; Ptrend = 0·71). Despite small differences by ethnicity, the interaction terms between coffee intake and ethnicity were not significant.
In this multiethnic population, regular, but not decaffeinated, coffee intake was much more protective against diabetes in women of all ethnic groups than in men.
Equol (EQ) is a metabolite produced by gut bacteria through the chemical reduction of the soya isoflavone daidzein (DE), but only by 30–60 % of the population. EQ is believed to provide benefits derived from soya intake and its production is widely viewed as a relatively stable phenomenon. In a randomised, cross-over intervention with soya foods, seventy-nine pre-menopausal women were challenged with a high-soya and a low-soya diet each for 6 months, separated by a 1-month washout period. Overnight urine was collected at three time points during each diet period and analysed for DE and EQ by liquid chromatography tandem MS. Remaining an EQ producer (EP) or non-producer (NP) or changing towards an EP or NP was assessed using an EQ:DE ratio of ≥ 0·018 combined with a DE threshold of ≥ 2 nmol/mg creatinine as a cut-off point. We observed 19 and 24 % EP during the low-soya and high-soya diet periods, respectively, and found that 6–11 % of our subjects changed EQ status ‘within’ each study period (on an average of 1·2 times), while 16 % changed ‘between’ the two diet periods. The present finding challenges the widely held conviction that EQ production within an individual remains stable over time. The precise factors contributing to changes in EQ status, however, remain elusive and warrant further investigation.
To compare the prevalence of modifiable risk factors for cancer and other chronic diseases between adult cancer survivors and persons with no history of cancer.
Population-based sample residing in California and Hawaii.
A total of 177 003 men and women aged 45–75 years who participated in the Multiethnic Cohort Study (MEC). Logistic regression was used to examine adherence to recommendations regarding modifiable risk factors among cancer survivors (n 16 346) when compared with cohort members with no history of cancer (n 160 657).
Cancer survivors were less likely than cohort members with no history of cancer to meet recommendations specified in the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 2007 report (OR = 0·97; 95 % CI 0·96, 0·99). No difference between groups was seen for adherence to dietary recommendations alone (OR = 0·99; 95 % CI 0·98, 1·01). Site-specific analyses showed that results for colorectal cancer were similar to those for all cancers combined, but survivors of breast (OR = 1·04; 95 % CI 1·02, 1·07) and prostate (OR = 1·04; 95 % CI 1·01, 1·07) cancer were more likely to meet dietary recommendations. Latino survivors were less likely to adhere to WCRF/AICR recommendations than Latino controls; however, differences across ethnic groups were not significant (Pinteraction = 0·64).
The modest differences found between adult cancer survivors and persons with no history of cancer suggest that a diagnosis of cancer in itself may not be associated with improvements in health behaviours related to cancer and other chronic diseases.
The present study explored the association between dietary vitamin D and non-Hodgkin's lymphoma (NHL) risk. The multiethnic cohort (MEC) includes more than 215 000 Caucasians, African Americans, Native Hawaiians, Japanese Americans and Latinos, aged 45–75. After 10 years of follow-up, 939 incident NHL cases were identified. Risk was estimated using proportional hazards' models adjusted for possible confounders. Vitamin D intake was not associated with NHL risk in the entire cohort (Ptrend = 0·72 for men and Ptrend = 0·83 for women), but significantly lowered disease risk in African American women (hazard ratio (HR) = 0·50, 95 % CI: 0·28, 0·90, Ptrend = 0·03) and was borderline protective in African American men (HR = 0·68; 95 % CI: 0·39, 1·19; Ptrend = 0·31) when the highest to the lowest tertile was compared. In NHL subtype analyses, a 19, 36 and 32 % lowered risk, although not significant, was observed for diffuse large B-cell lymphoma, follicular lymphoma and small lymphocytic lymphoma/chronic lymphocytic leukemia in women, respectively. High dietary intake of vitamin D did not show a protective effect against NHL within the MEC except among African Americans, possibly because vitamin D production due to sun exposure is limited in this population.
The present analysis investigated the effect of soya foods on serum levels of six inflammatory markers, leptin, adiponectin, monocyte attractant protein 1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), IL-6 and C-reactive protein (CRP), and their relationship with BMI and lifetime soya intake. We randomised twenty-four men to a high- (two daily servings with 30–35 mg isoflavones per serving) or a low-soya diet for 3 months. After a 1-month washout period, the men crossed over to the other treatment. We used a multiplex bead immunoassay to measure leptin, adiponectin, MCP-1 and MIP-1b and ELISA assays for IL-6 and CRP. The statistical analysis applied mixed models that incorporated the four repeated measurements. The men had a mean age of 58·7 (sd 7·2) years and a mean BMI of 28·4 (sd 4·9) kg/m2. We observed no significant intervention effect of the soya treatment on any of the six markers. After adjustment for age and ethnicity, highly significant associations of BMI and body weight with leptin and MCP-1 emerged. Men with high soya intake early in life also had higher levels of leptin and MCP-1, whereas no association was seen for soya intake during adulthood. MIP-1b, adiponectin, IL-6 and CRP were not related to BMI, body weight or soya intake at any time in life. No intervention effect of soya foods on markers of inflammation was observed in this small study, but adiposity and early-life soya intake were related to higher leptin and MCP-1 levels.
Based on the hypothesis that isoflavones are absorbed more efficiently from fermented than from non-fermented soya foods, we compared the urinary isoflavonoid excretion (UIE) after intake of miso soup or soya milk. We recruited twenty-one women with Japanese ancestry who consumed standardized soya portions containing 48 mg isoflavones. On day 1, half the women consumed soya milk, the other half started with miso soup. On day 3, the subjects ate the other soya food and on day 5, they repeated the first food. Each participant collected a spot urine sample before and an overnight urine sample after soya food intake. All urine samples were analysed for daidzein, genistein and equol using LC–MS and were expressed as nmol/mg creatinine. We applied mixed models to evaluate the difference in UIE by food while including the baseline values and covariates. Relative to baseline, both groups experienced significantly higher UIE after consuming any of the soya foods. We observed no significant difference in UIE when soya milk was compared to miso soup (P = 0·87) among all women or in the seven equol producers (P = 0·88). Repeated intake of the same food on different days showed high reproducibility within subjects. These preliminary results indicate similar UIE after consuming a fermented soya food (miso) as compared to a non-fermented soya food (soya milk). Therefore, recommendations favouring fermented soya foods are not justified as long as the intestinal microflora is capable of hydrolysing the isoflavone glucosides from non-fermented soya foods.
The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk.
To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women.
A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake.
After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend = 0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (−8% between the lowest and highest quartiles of intake, Ptrend = 0.06), but not oestrogens. Similarly, consumption of fruits (−12%, Ptrend = 0.03), vegetables (−9%, Ptrend = 0.15) and whole grains (−7%, Ptrend = 0.07) showed inverse associations with androstenedione levels.
The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.
To compare the dietary habits of Japanese women in Japan with those of Japanese and Caucasian women living in Hawaii.
Data from two previous cross-sectional studies conducted within two years in Hawaii and Gifu, Japan were pooled and analysed. Dietary intakes were assessed with validated food-frequency questionnaires and urine samples were collected for isoflavone measurement.
Participants were recruited through mammography clinics in both locations.
In Hawaii, 164 Caucasian and 146 Japanese women; in Japan, 206 women.
Dietary habits differed considerably by ethnicity and location. In comparison to the Caucasian diet, the diet in Japan was relatively low in fat and high in carbohydrates and protein, whereas the Japanese women in Hawaii reported intermediate intakes. Japanese women in Gifu consumed a diet that was relatively high in fish, soy, eggs and vegetables, and low in fruits, dairy products and meat. In contrast, the Caucasian women consumed the most dairy products and fruits and the Japanese women in Hawaii reported the highest grain and meat intakes.
The diet of Japanese women in Hawaii appeared to be a combination of foods eaten in Japan and the dietary habits of Caucasian women in Hawaii, but eating habits in Japan are also different from traditional nutritional patterns. This study illustrates several problems related to dietary comparisons across populations and provides information for future investigations on chronic disease risk.
Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5–22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0·04) and the IGF-1:IGFBP-3 ratio (P=0·06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.
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