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.

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.

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.