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IntroductionGalacto-oligosaccharides (GOS) are well-substantiated prebiotic substrates. Multiple studies have demonstrated a positive impact of GOS on gut microbiota composition and activity, so-far mainly related to Bifidobacterium. However, data on the beneficial impact at lower dosages in a healthy female population are limited. The primary aim of the current study was to reveal the effect of low dosages (1.3 and 2.0 g) of GOS on fecal Bifidobacterium abundance in healthy women. Other outcomes included the effect of low dosage of GOS on overall fecal microbiota composition and on self-perceived GI comfort, sleep quality and mental wellbeing.MethodEighty-eight healthy women (42–70 years, BMI 18.7–30 kg/m2) were included in this randomized, parallel, double-blind study of 6 weeks. The participants were stratified for fiber intake, BMI and age and randomized to consume either 1.3 or 2.0 g of GOS per day for 3 weeks after a control period of 3 weeks without any intervention. Fecal samples were collected for shotgun metagenomics sequencing at the start (t = −3) and end (t = 0) of the control period and at the end of the intervention period (t = 3). Self-perceived gut comfort, sleep quality, and mental wellbeing were assessed weekly. Hierarchical clustering of principal components was applied to data collected from study participants.ResultsThe relative abundance of Bifidobacterium in feces increased significantly after 3 weeks of daily consumption of both 1.3 g (p

IntroductionAn elevated postprandial glucose response is associated with an increased risk of cardiometabolic diseases. Existing research suggests large heterogeneity in the postprandial glucose responses to identical meals and food products between individuals, but the effect of other consumed meals during the day and the order of meals during the day on the heterogeneity in postprandial glucose responses still needs to be investigated. In addition, the robustness of the glucose responses to meals or foods is still unknown.ObjectivesThe overall aim of the project is to assess whether the glucose response to a meal is sufficiently person-specific to use in personalized dietary advice. We aim to answer the question: “How replicable are glucose responses to meals within individuals and how consistent is the variation in glucose responses between individuals?”MethodsThe question will be assessed under standardized conditions of a 9-week fully controlled dietary intervention in which all meals are the same between individuals and consumed in a fixed order at a fixed time. 63 apparently healthy men and women with a BMI of 25–40 kg/m2 and aged 45–75 years were enrolled in the RepEAT study (NCT05456815), of whom 53 participants completed the study. The RepEAT study comprised a fully controlled dietary intervention of nine weeks, consisting of three repetitive periods of three weeks. Within each three-week period, a variety of meals and food products were offered during breakfast, lunch, dinner and in between meal snacks. Throughout the dietary intervention, glucose was continuously monitored using Freestyle Libre Pro IQ monitors. Physical activity was monitored using the ActiGraph and ActivPAL. To measure the association between glucose responses and an individual’s phenotype, various measurements were performed before the start of the dietary intervention including an oral glucose tolerance test, a high-fat mixed meal challenge, assessment of body fat distribution including liver fat (MRI/MRS), and cardiometabolic markers.DiscussionThe repetitive and fully controlled nature of the dietary study allows detailed assessment of the replicability of the glucose responses to meals and food products within individuals. Furthermore, the consistency of the variation between individuals independent of insulin resistance will be determined.

The experimental challenge with attenuated enterotoxigenic E. coli strain E1392/75-2A prevents diarrhea upon a secondary challenge with the same bacteria. A dose-response pilot study was performed to investigate which immunological factors are associated with this protection. Healthy subjects were inoculated with increasing E. coli doses of 1E6-1E10 CFU, and three weeks later, all participants were rechallenged with the highest dose (1E10 CFU). Gastrointestinal discomfort symptoms were recorded, and stool and blood samples were analyzed. After the primary challenge, stool frequency, diarrhea symptom scores, and E. coli-specific serum IgG (IgG-CFA/II) titer increased in a dose-dependent manner. Fecal calprotectin and serum IgG-CFA/II response after primary challenge were delayed in the lower dose groups. Even though stool frequency after the secondary challenge was inversely related to the primary inoculation dose, all E. coli doses protected against clinical symptoms upon rechallenge. Ex vivo stimulation of PBMCs with E. coli just before the second challenge resulted in increased numbers of IL-6+/TNF-α+ monocytes and mDCs than before the primary challenge, without dose-dependency. These data demonstrate that primary E. coli infection with as few as 1E6 CFU protects against a high-dose secondary challenge with a homologous attenuated strain. Increased serum IgG-CFA/II levels and E. coli-induced mDC and monocyte responses after primary challenge suggest that protection against secondary E. coli challenges is associated with adaptive as well as innate immune responses.

Kori-tofu is a frozen soy tofu, and soy consumption is associated with positive effects on cardiometabolic health markers. We aimed to assess the potential of Kori-tofu to improve cardiometabolic health outcomes in humans by repetitive daily consumption. In a double-blind randomized controlled cross-over trial, 45 subjects aged 40–70 years with (mildly) elevated cholesterol levels, received a four week Kori-tofu intervention or whey protein control intervention with a four week wash-out period in between. Cardiometabolic biomarkers were measured before and after both interventions. A significant decrease in total, low-density lipids (LDL), and high-density lipids (HDL) cholesterol, Hemoglobin A1c (HbA1c), fructosamine and systolic blood pressure was observed within the Kori-tofu intervention. However, many of these findings were also observed in the control intervention. Only adiponectin changes were different between treatments but did not change significantly within interventions. Improvements in cardiometabolic markers within the Kori-tofu intervention point toward potential beneficial health effects. Due to the lack of significant effects as compared to control, there is, however, currently no substantiating evidence to claim that Kori-tofu has beneficial effects on cardiometabolic health.

Infectious diseases are a major cause of morbidity and mortality worldwide. Nutritional interventions may enhance resistance to infectious diseases or help to reduce clinical symptoms. Here, we investigated whether a whey protein concentrate (WPC) could decrease diarrheagenic Escherichia coli-induced changes in reported stool frequency and gastrointestinal complaints in a double-blind, parallel 4-week intervention study. Subjects were randomly assigned to a whey hydrolysate placebo group, a low-dose WPC group or a high-dose WPC group. After 2 weeks of consumption, subjects (n = 121) were orally infected with a high dose of live but attenuated diarrheagenic E. coli (strain E1392/75-2A; 1E10 colony-forming units). Subjects recorded information on stool consistency and the frequency and severity of symptoms in an online diary. The primary outcome parameters were a change in stool frequency (stools per day) and a change in Gastrointestinal Symptom Rating Scale (GSRS) diarrhea score between the first and second days after infection. Neither dose of the whey protein concentrate in the dietary treatment affected the E. coli-induced increase in stool frequency or GSRS diarrhea score compared to placebo treatment. The composition of the microbiota shifted between the start of the study and after two weeks of consumption of the products, but no differences between the intervention groups were observed, possibly due to dietary guidelines that subjects had to adhere to during the study. In conclusion, consumption of the whey protein concentrate by healthy adults did not reduce diarrhea scores in an E. coli infection model compared to a whey hydrolysate placebo control.

People experiencing sleep problems may benefit from nutrients supporting serotonin metabolism and stress reduction. We studied the effect of a dairy-based product (DP) containing protein, galacto-oligosaccharides, vitamins and minerals, on sleep quality, stress, and gut-microbiota. In a cross-over RCT (three weeks intervention; three weeks washout), adults (n = 70; 30–50 y) with sleep disturbances (Pittsburgh Sleep Quality Index (PSQI) ≥ 9) consumed products 1 h before bed-time. Sleep quality (PSQI) was measured weekly, stress at base- and end-line (Depression Anxiety Stress Scale and saliva cortisol). Fecal samples were collected in the 1st intervention period only. Compared to placebo (skimmed milk), PSQI was only lower at day 14 in the 2nd intervention period in intention-to-treat (ITT) (p = 0.017; n = 69) and per-protocol (PP) (p = 0.038; n = 64) analyses. Post-hoc analysis (modified-PP: n=47, with baseline PSQI ≥ 9, and endline day 14), however, showed a decrease in PSQI (−1.60 ± 2.53; p = 0.034). Early morning saliva cortisol decreased versus placebo (p = 0.045). Relative abundance of Bifidobacterium increased (p = 0.02). Redundancy analysis showed an inverse relationship between baseline microbiota composition and baseline PSQI (p = 0.046). Thus, although DP did not improve sleep quality in ITT and PP populations, it did in the modPP. DP reduced salivary cortisol and stimulated Bifidobacterium, which possibly is important for sleep improvement.