Mads Vendelbo Lind

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet–gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (–0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Increasing evidence indicates that the gut microbiome (GM) plays an important role in dyslipidemia. To date, however, no in-depth characterization of the associations between GM with lipoproteins distributions (LPD) among adult individuals with diverse BMI has been conducted. To determine such associations, we studied blood-plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 Danes aged 19–89 years. Stratification of LPD segregated subjects into three clusters displaying recommended levels of lipoproteins and explained by age and body-mass-index. Higher levels of HDL2a and HDL2b were associated with a higher abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL-1 and LDL-2 were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome-sequencing showed a higher abundance of biosynthesis of multiple B-vitamins and SCFA metabolism genes among healthier LPD profiles. Metagenomic-assembled genomes (MAGs) affiliated to Eggerthellaceae and Clostridiales were contributors of these genes and their relative abundance correlated positively with larger HDL subfractions. The study demonstrates that differences in composition and metabolic traits of the GM are associated with variations in LPD among the recruited subjects. These findings provide evidence for GM considerations in future research aiming to shed light on mechanisms of the GM–dyslipidemia axis.

The food availability and dietary behaviours in Greenland have changed with increasing Westernisation. Food reward is an important driver of food choice and intake, which has not previously been explored in the Arctic population. The aim of this study was to explore differences in food reward after a four-week intervention period with a traditional Inuit diet (TID) or Westernised diet (WD) in Inuit populations in Northern and Western Greenland. This cross-sectional analysis included 44 adults (n = 20 after TID and n = 24 after WD). We assessed the food reward components, explicit liking and implicit wanting, using the Leeds Food Preference Questionnaire under standardised conditions 60 min after drinking a glucose drink as part of an oral glucose tolerance test after four weeks following a TID or WD. The food intake was assessed using food frequency questionnaires. The intervention groups differed only in implicit wanting for high-fat sweet foods, with higher implicit wanting among the participants following TID compared to WD. Both groups had lower explicit liking and implicit wanting for sweet relative to savoury foods and for high-fat relative to low-fat foods. This exploratory study can guide future studies in Inuit populations to include measures of food reward to better understand food intake in the Arctic.

Lipoprotein subfractions are biomarkers for the early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time-consuming, and there is a need to develop a rapid method for cohort screenings. This study presents partial least-squares regression models developed using ¹H nuclear magnetic resonance (NMR) spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. This study explores, for the first time, different regions of the ¹H NMR spectrum representing signals of molecules in lipoprotein particles and different lipid species to develop parsimonious, reliable, and optimal prediction models. A total of 65 lipoprotein main and subfractions were predictable with high accuracy, Q² of >0.6, using an optimal spectral region (1.4–0.6 ppm) containing methylene and methyl signals from lipids. The models were subsequently tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85–95%. In addition, an open software tool was developed to predict lipoproteins concentrations in human blood from standardized ¹H NMR spectral recordings.

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promotedBifidobacteriumspecies convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability ofBifidobacteriumspecies to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degradingBifidobacteriumspecies containing the ALDH, includingBifidobacterium longum,B. breveandB. bifidum. We further demonstrate that faecal concentrations ofBifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4⁺T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA₃). Our findings reveal that breastmilk-promotedBifidobacteriumspecies produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

Breastfeeding protects against diseases, with potential mechanisms driving this being human milk oligosaccharides (HMOs) and the seeding of milk-associated bacteria in the infant gut. In a cohort of 34 mother–infant dyads we analyzed the microbiota and HMO profiles in breast milk samples and infant’s feces. The microbiota in foremilk and hindmilk samples of breast milk was compositionally similar, however hindmilk had higher bacterial load and absolute abundance of oral-associated bacteria, but a lower absolute abundance of skin-associated Staphylococcus spp. The microbial communities within both milk and infant’s feces changed significantly over the lactation period. On average 33% and 23% of the bacterial taxa detected in infant’s feces were shared with the corresponding mother’s milk at 5 and 9 months of age, respectively, with Streptococcus, Veillonella and Bifidobacterium spp. among the most frequently shared. The predominant HMOs in feces associated with the infant’s fecal microbiota, and the dominating infant species B. longum ssp. infantis and B. bifidum correlated inversely with HMOs. Our results show that breast milk microbiota changes over time and within a feeding session, likely due to transfer of infant oral bacteria during breastfeeding and suggest that milk-associated bacteria and HMOs direct the assembly of the infant gut microbiota.

Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength. To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults. In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3–5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition. There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm²; 95% CI, +0.41 to +2.95 cm²; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10⁻⁴) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10⁻⁵). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01). Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.