Abstract
Context
Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma ...metabolome might reflect differences in the gut microbiome.
Objective
To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota.
Design
Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography–mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants.
Results
BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PCBMI). In addition to glutamate, PCBMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PCBMI (P < 8.0e-4 for all). When simultaneously regressing PCBMI and metabolite-associated gut bacteria against BMI, only PCBMI remained statistically significant.
Conclusions
We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.
We identified metabolites associated with BMI. The BMI-related metabolites were connected to four microbiota genera, suggesting a mediating role of the metabolites in the microbiota–obesity relationship.
The aim of this study was to explore the longitudinal association between reported baseline water intake and incidence of coronary artery disease (CAD) and type 2 diabetes in the Malmö Diet and ...Cancer Cohort (n = 25,369). Using cox proportional hazards models, we separately modelled the effect of plain and total (all water, including from food) water on CAD and type 2 diabetes risk, whilst adjusting for age, sex, diet collection method, season, smoking status, alcohol intake, physical activity, education level, energy intake, energy misreporting, body mass index, hypertension, lipid lowering medication, apolipoprotein A, apolipoprotein B, and dietary variables. Sensitivity analyses were run to assess validity. After adjustment, no association was found between tertiles of plain or total water intake and type 2 diabetes risk. For CAD, no association was found comparing moderate to low intake tertiles from plain or total water, however, risk of CAD increased by 12% (95% CI 1.03, 1.21) when comparing high to low intake tertiles of plain water, and by 17% (95% CI 1.07, 1.27) for high versus low tertiles of total water. Sensitivity analyses were largely in agreement. Overall, baseline water intake was not associated with future type 2 diabetes risk, whilst CAD risk was higher with higher water intakes. Our findings are discordant with prevailing literature suggesting higher water intakes should reduce cardiometabolic risk. These findings may be an artefact of limitations within the study, but future research is needed to understand if there is a causal underpinning.
As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, ...genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called
missing heritability
to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
Purpose
Elevated plasma concentration of the vasopressin marker copeptin and low water intake are associated with elevated blood glucose and diabetes risk at a population level. Moreover, in ...individuals with low urine volume and high urine osmolality (u-Osm), water supplementation reduced fasting plasma (fp) copeptin and fp-glucose. In this observational study, we investigated if low total water intake or high u-Osm correlated with high fp-copeptin and components of the metabolic syndrome at the population level.
Methods
In the population-based Malmö Offspring Study (MOS,
n
= 2599), fp-copeptin and u-Osm from morning urine samples were measured, and diet and total water intake (from beverages and food moisture) was assessed by a 4-day web-based record.
Results
Increasing water intake by tertile was after adjustment for age and sex associated with low fp-triglycerides (
p
= 0.002) and high fp-HDL (
p
= 0.004), whereas there was no association with the other investigated metabolic traits (HbA1c, fp-glucose, BMI or waist circumference). Increasing u-Osm by tertile was, after adjustment for age and sex, associated with high fp-glucose (
p
= 0.007), and borderline significantly associated with high HbA1c (
p
= 0.053), but no association was observed with fp-HDL, fp-triglycerides, BMI or waist circumference. Fp-copeptin concentration correlated significantly with water intake (
r
= − 0.13,
p
< 0.001) and u-Osm (
r
= 0.27,
p
< 0.001). High copeptin was associated with all investigated metabolic traits (
p
< 0.001 for all).
Conclusion
Low concentrations of the vasopressin marker copeptin is linked to high water intake, low u-Osm, and a favorable metabolic profile, suggesting that vasopressin lowering lifestyle interventions, such as increased water intake, may promote metabolic health.
BACKGROUND: The fat mass and obesity-associated gene (FTO) has been shown to be associated with obesity and to influence appetite regulation. OBJECTIVE: The aim was to examine whether dietary factors ...(macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m²). DESIGN: A cross-sectional study examined 4839 subjects in the population-based Malmö Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO (rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities. RESULTS: Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 (95% CI: 25.8, 26.8) among AA carriers (P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes (BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity (P for trend = 0.004, P for interaction = 0.05). CONCLUSION: Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.
Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with ...unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective.
We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided.
A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified.
Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.77; 95% CI: 0.68, 0.87; P-trend < 0.001). Most robust inverse associations were seen for intakes of cream and high-fat fermented milk (P-trend < 0.01) and for cheese in women (P-trend = 0.02). High intake of low-fat dairy products was associated with increased risk, but this association disappeared when low- and high-fat dairy were mutually adjusted (P-trend = 0.18). Intakes of both high-fat meat (P-trend = 0.04) and low-fat meat (P-trend < 0.001) were associated with increased risk. Finally, we did not observe significant association between total dietary fat content and T2D (P-trend = 0.24), but intakes of saturated fatty acids with 4-10 carbons, lauric acid (12:0), and myristic acid (14:0) were associated with decreased risk (P-trend < 0.01).
Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. Meat intake was associated with increased risk independently of the fat content.
Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on ...sugar-sweetened beverages (SSBs), not sugar per se.
The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, and mortality risk.
Two prospective population-based cohorts were examined: the Malmö Diet and Cancer Study (MDCS; n = 24,272), which collected dietary data by combining a food diary, interview, and food-frequency questionnaire (FFQ), and the Northern Swedish Health and Disease Study (NSHDS; n = 24,475), which assessed diet with an FFQ. Sugar intakes defined as both added and free sugar and different sugar sources were examined. The associations with mortality were examined using a multivariable Cox proportional hazards regression.
Higher sugar consumption was associated with a less favorable lifestyle in general. The lowest mortality risk was found with added sugar intakes between 7.5% and 10% of energy (E%) intake in both cohorts. Intakes >20E% were associated with a 30% increased mortality risk, but increased risks were also found at intakes <5E% 23% in the MDCS and 9% (nonsignificant) in the NSHDS. Similar U-shaped associations were found for both cardiovascular and cancer mortality in the MDCS. By separately analyzing the different sugar sources, the intake of SSBs was positively associated with mortality, whereas the intake of treats was inversely associated.
Our findings indicate that a high sugar intake is associated with an increased mortality risk. However, the risk is also increased among low sugar consumers, although they have a more favorable lifestyle in general. In addition, the associations are dependent on the type of sugar source.
Studies have shown conflicting associations between the salivary amylase gene (
) copy number and obesity. Salivary amylase initiates starch digestion in the oral cavity; starch is a major source of ...energy in the diet.
We investigated the association between
copy number and obesity traits, and the effect of the interaction between
copy number and starch intake on these obesity traits.
We first assessed the association between
copy number (genotyped by digital droplet polymerase chain reaction) and obesity traits in 4800 individuals without diabetes (mean age: 57 y; 60% female) from the Malmö Diet and Cancer Cohort. Then we analyzed interactions between
copy number and energy-adjusted starch intake (obtained by a modified diet history method) on body mass index (BMI) and body fat percentage.
copy number was not associated with BMI (
= 0.80) or body fat percentage (
= 0.38). We observed a significant effect of the interaction between
copy number and starch intake on BMI (
-interaction = 0.007) and body fat percentage (
-interaction = 0.03). Upon stratification by dietary starch intake, BMI tended to decrease with increasing
copy numbers in the low-starch intake group (
= 0.07) and tended to increase with increasing
copy numbers in the high-starch intake group (
= 0.08). The lowest mean BMI was observed in the group of participants with a low
copy number and a high dietary intake of starch.
Our findings suggest an effect of the interaction between starch intake and
copy number on obesity. Individuals with high starch intake but low genetic capacity to digest starch had the lowest BMI, potentially because larger amounts of undigested starch are transported through the gastrointestinal tract, contributing to fewer calories extracted from ingested starch.
Purpose
It has been suggested that a high intake of sugar or sweeteners may result in an unfavorable microbiota composition; however, evidence is lacking. Hence, in this exploratory epidemiological ...study, we aim to examine if intake of added sugar, sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) associate with the gut microbiota composition.
Methods
Participants (18–70 years) in the Malmö Offspring Study have provided blood, urine, and fecal samples and completed both web-based 4 day food records and short food frequency questionnaires. The gut microbiota was assessed by 16S rRNA sequencing, processed in QIIME and matched to Greengenes (v.13.8), giving 64 included genera after filtering. Intake of added sugar (
n
= 1371) (also supported by the overnight urinary sugar biomarker in a subgroup
n
= 577), SSBs (
n
= 1086) and ASBs (
n
= 1085) were examined as exposures in negative binomial regressions.
Results
Various genera nominally associated with intake of added sugar, SSBs, and ASBs. Only the negative association between SSB intake and
Lachnobacterium
remained significant after multiple testing correction. A positive association between SSB intake and the Firmicutes:Bacteroidetes ratio was also observed.
Conclusion
In this wide population, the cross-sectional associations between added sugar and sweet beverage intake and the gut microbiota are modest, but the results suggest that SSB intake is associated negatively with the genus
Lachnobacterium
and positively with the Firmicutes:Bacteroidetes ratio. Larger studies, preferably using metagenomic sequencing, are needed to further evaluate if a link exists between intake of sugars and sweeteners and the human gut microbiota.
While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity ...on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study.
Out of 26,615 adults (45-74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk.
All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk.
A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.
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