Effects of 4G-beta-D-Galactosylsucrose in patients with depression: A randomized, double-blinded, placebo-controlled, parallel-group comparative study.

Advances in genetic research on microbiome have led to several trials on the effectiveness of synbiotics or probiotics in patients with depression; however, none have evaluated the efficacy of prebiotics. 4G-beta-D-Galactosylsucrose (Lactosucrose, LS) is selectively assimilated by Bifidobacterium as a prebiotic and improves microbiome diversity. However, as it is not clear if LS consumption can improve symptoms of depression, we investigated whether LS intake can improve depressive symptoms, quality of life (QOL), and self-efficacy by conducting a single cite, double-blinded, randomized controlled trial in 20 outpatients with depressive episodes (F32, ICD-10) for 24 weeks. Participants (age range, 36-72 years) were randomized to the LS (n = 9) or placebo groups (n = 11). Primary outcome was improvement in total Montgomery Asberg Depression Rating Scale (MADRS) score, and the secondary outcomes were MADRS subscores, global self-efficacy scale (GSES) score, World Health Organization QOL (WHO/QOL-26) score, and 16S rRNA analysis of the fecal microbiome. LS consumption did not significantly improve total MADRS scores (-2 (-16 to 16) vs 0 (-6 to 10), p = 0.552), but GSES tended to improve in the LS group (2.00 ± 4.24 vs -1.36 ± 4.15, p = 0.091) with a large effect size (Cohen's d = 0.802). Sequencing of 16S rRNA revealed individual-level differences in microbiome diversity changes due to the intervention. Thus, we show that LS intake can improve self-efficacy, but not depressive symptoms, even in a small sample. Additional studies that also regulate diet and ensure adherence may help determine a correlation between depression and the gut microbiome.

Clinical trial of glutamate for the improvement of nutrition and health in the elderly.

Dietary free-glutamate (Glu) improves taste and palatability. In our previous study, we found that Glu intake by hospitalized elderly was low and supplementation of monosodium L-glutamate (MSG) to their staple diet improved their behavior. To confirm such findings, we conducted a double-blind and placebo-controlled trial in hospitalized elderly. The study consisted of a 1-month lead-in period, a 3-month intervention period, and a 1-month follow-up period. In the intervention group, 0.5% (w/w) MSG was added to every staple diet, 150 g of rice gruel (the MSG group). Fourteen subjects in the MSG group (average age 83.0 +/- 8.9 years) and 15 in the control group (average age 84.3 +/- 9.6 years) completed the study. The subjects of both groups took most of the given foods based on the energy requirement of each subject's metabolic rate, body weight, and activity. In the last week of each period, nurses assessed the dementia score and daily performance of both groups. The daily performance was improved by dietary MSG. Behavior during mealtime was video-recorded for 5 min in the lead-in period and after 3 months in the intervention period. Significant improvement in the mealtime behavior was observed only in the MSG group. Furthermore, although serum albumin itself did not increase, the ratio of reduced-form albumin to total albumin increased only in the MSG group. In conclusion, supplementation of 0.5% MSG to rice gruel three times a day for 3 months improved behaviors and the nutritional status of hospitalized elderly.

Genistein enhances antigen-specific cytokine production in female DO11.10 transgenic mice.

Genistein is a phytoestrogen contained at high levels in soy products and has been shown to regulate immunoresponse. In this study, we evaluated the effects of genistein on the production of cytokines from antigen (Ag)-specific T cells using DO11.10 transgenic mice because the direct effect of genistein on Ag-specific cytokine production has not been elucidated. The oral administration of 20 mg/kg genistein increased IFN-gamma and IL-4 production from DO11.10+ T cells in response to ovalbumin (OVA)323-339 peptide in female DO11.10 mice. Analysis of intracellular cytokine synthesis revealed that the percentages of cytokine-producing cells in the control and genistein-treated groups were not different, indicating that increased cytokine production occurred at the single-cell level. In contrast to the female mice, genistein did not increase cytokine production in male mice, suggesting that the effect of genistein on cytokine production is gender-dependent.

Protein deficiency impairs DNA vaccine-induced antigen-specific T cell but not B cell response in C57BL/6 mice.

DNA vaccination is a simple method to induce antigen (Ag)-specific immunoresponse and has many potential advantages over other vaccines. Although people who need to receive vaccines often suffer undernutrition, there has been no study on a how nutritional status affects the immunoresponse induced by DNA vaccination. The aim of this study was to determine the relationship between protein deficiency and DNA vaccine-induced immunoresponses. C57BL/6 mice were fed a 5% or 20% casein diet for 30 d. The mice were immunized with an ovalubumin (OVA)-expression plasmid by the gene gun-based method three times at 10-d intervals. Body weight and serum albumin concentration in protein-deficient mice were significantly lower than those in mice fed the 20% casein diet (p<0.01, p<0.05). The percentage of OVA-specific CD8+ T cells was significantly decreased in the 5% casein group compared to that in the 20% casein group (p<0.05). Furthermore, CD4+ T cells from mice fed the low-protein diet showed lower interleukin (IL)-2 production than did those from the 20% group. In contrast to the T-cell function, protein deficiency did not affect OVA-specific Ab responses (p>0.05). These results suggest that protein deficiency impairs the induction of Ag-specific T-cell but not B-cell response in DNA-immunized mice. Our observation indicates that, in addition to development of an effective of DNA vaccine, the management of nutritional state is important for the prevention of infectious disease by DNA vaccination.

Genistein suppresses antigen-specific immune responses through competition with 17beta-estradiol for estrogen receptors in ovalbumin-immunized BALB/c mice.

OBJECTIVE: The aim of this study was to determine the effects of phytoestrogen genistein on antigen (Ag)-specific immune responses and elucidate the mechanisms underlying those effects. METHODS: Ovalbumin (OVA)-immunized BALB/c mice were administered genistein for 35 d, and OVA-specific immune responses were examined by measuring OVA-specific proliferative responses, production of cytokines, and antibody responses. To assess the effect of genistein on antibody responses to thymus-independent Ag, mice were immunized with 2,4,6-trinitrophenyl (TNP)-Ficoll instead of OVA. Effect of genistein on the functions of CD11c(+) dendritic cells was also examined. Finally, to determine the contribution of estrogen receptor to genistein-mediated immune regulation, mice that had been administered genistein were treated with the estrogen receptor antagonist ICI 182,780 and OVA-specific proliferative responses were examined. RESULTS: OVA-specific proliferative responses and interferon-gamma production levels were decreased in mice administered 20 mg/kg genistein compared with those in control mice without reduction in responses to anti-CD3 monoclonal (m)antibody. The level of OVA-specific immunoglobulin (Ig)G1 was also decreased in mice administered genistein. Levels of OVA-specific IgG2a and IgG2b production and interleukin-4 production in response to OVA were not significantly different but tended to decrease in genistein-treated mice. Genistein administration did not influence the TNP-specific IgM and IgG levels. Furthermore, genistein did not affect the Ag-presenting activity of CD11c(+) dendritic cells. Treatment with ICI 182,780 decreased OVA-specific proliferative responses, but genistein did not suppress these responses synergistically in mice treated with ICI 182,780. CONCLUSIONS: The results of this study suggest that genistein suppresses Ag-specific immune responses. The mechanism underlying the suppression is responsible for the competition of genistein with endogenous 17beta-estradiol for estrogen receptors.

Deletion polymorphisms in the promoter region of Fcgamma receptor IIB is not associated with antigen-specific IgG2a and IgG2b antibody responses in NC/Nga mice.

Fcgamma receptor (R) IIB, a low-affinity FcR for IgG, inhibits B cell Ag R (BCR)-mediated activation when these two receptors are cross-linked by Ag and IgG-containing immune complexs (ICs). We found deletion polymorphisms in the promoter region of fcgr2b in NC/Nga mice, a model for human atopic dermatitis. NC/Nga mice produced significantly higher levels of ovalbumin (OVA)-specific IgG, IgG2a and IgG2b than did BALB/c mice. Analysis of (BALB/c x NC/Nga)F1 x BALB/c or (BALB/c x NC/Nga) F1 x NC/Nga backcross mice revealed that deletion polymorphisms of fcgr2b in NC/Nga mice does not directly regulate hyper OVA-specific IgG2a and IgG2b Ab responses.

Defect of toll-like receptor 9-mediated activation in NC/Nga mouse macrophages.

Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). In this study, we examined TLR9-mediated activation in NC/Nga mice, an animal model for human atopic dermatitis. NC/Nga mouse macrophages produced significantly less TNF-alpha than did BALB/c mouse macrophages in response to CpG oligonucleotide (ODN). In addition to defective TLR9-mediated TNF-alpha production, phosphorylation of ERK1,2 and p38 was rapidly diminished after 60 min of CpG ODN stimulation, whereas phosphorylation of these molecules was sustained until 60 min in BALB/c mice. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was not observed in NC/Nga mouse macrophages. In contrast, B cells and dendritic cells (DCs) from NC/Nga mice showed normal responses to CpG ODN stimulation. The expression level of TLR9 in NC/Nga mouse macrophages was significantly lower than that in BALB/c mouse macrophages, whereas levels of TLR9 expression in B cells and DCs in NC/Nga mice were the same as those in BALB/c mice. These results suggest that defective TLR9-mediated activation in NC/Nga mouse macrophages contributes to the reduction of TLR9 expression levels.

Oolong tea increases energy metabolism in Japanese females.

Oolong tea is a traditional Chinese tea that has long been believed to be beneficial to health such as decreasing body fat. We were interested in this assertion and tried to evaluate the effect of oolong tea on energy expenditure (EE) in comparison with green tea. The subjects were eleven healthy Japanese females (age 20+/-1 y; body mass index (BMI) 21.2+/-2.5 kg/m2) who each consumed of three treatments in a crossover design: 1) water, 2) oolong tea, 3) green tea. Resting energy expenditure (REE) and EE after the consumption of the test beverage for 120 min were measured using an indirect calorimeter. The cumulative increases of EE for 120 min were significantly increased 10% and 4% after the consumption of oolong tea and green tea, respectively. EE at 60 and 90 min were significantly higher after the consumption of oolong tea than that of water (P<0.05). In comparison with green tea, oolong tea contained approximately half the caffeine and epigallocatechin galate, while polymerized polyphenols were double. These results suggest that oolong tea increases EE by its polymerized polyphenols.

Glutamine and arginine affect Caco-2 cell proliferation by promotion of nucleotide synthesis.

OBJECTIVE: We tested our hypothesis that 1) the major effect of Gln is as a nitrogen donor, not an energy source, for nucleotides (NT) and 2) the supplementation of culture medium with arginine (Arg) decreases the flux of glutamine (Gln) for conversion to Arg, thus accelerating NT synthesis. METHODS: Various concentrations of nucleosides (NS+NT) Gln, and glutamate (Glu) in culture were tested for their effect on Caco-2 cell proliferation. (Arg was tested in media with and without Gln to evaluate the Gln pathway. The incorporation of (15)N from L-[5-(15)N]-Gln into NTs of DNA was measured under different NS + NT and Arg concentrations.) RESULTS: The proliferation of Caco-2 cells was increased by NS + NT and Gln supplementation, but not by Glu. The effective concentration of NS + NT was 100-fold smaller than that of Gln. An Arg effect was observed only in the presence of Gln. The NT synthesis from Gln, as indicated by (15)N incorporation from L-[5-(15)N]-Gln, was increased by Arg supplementation and decreased by NS + NT supplementation. CONCLUSION: These results support our hypothesis that the effects of Gln and Arg on Caco-2 cell proliferation are by the promotion of NT synthesis and that the major role of Gln is not energy supply.

Nutrition during pregnancy may be associated with allergic diseases in infants.

The prevalence of allergic diseases is high in Japan, even in infants. Their risk for developing allergies is influenced by the antigens in the mother's diet during pregnancy. We hypothesized that, apart from the antigens, hypersensitivity induced through high energy and nutrient intake by mothers during pregnancy may be a factor for allergic diseases in their babies. In this study, we tried to confirm our hypothesis. Allergy histories of parents and their infants, body characteristics and food and nutrient intake were measured by a questionnaire and a food frequency questionnaire, respectively. A total of 2,642 responses were obtained (return rate, 94.7%). The major allergic diseases in the infants were atopic dermatitis (6.0%), food allergy (3.7%) and bronchial asthma or asthmatic bronchitis (3.2%). About 60% of the infants with allergies had a family history of allergies. Family history of allergy, age of infant, order of birth, head and chest circumferences of infants, BMI of mothers before pregnancy and delivery and intake of lipids (fat and vegetable oil) and vegetables by mothers related positively, and the intake of protein, carbohydrates and milk and its products correlated negatively with allergic diseases in the infants (p < 0.05). The results, together with previous reports, suggest that a high intake of energy and lipids (fat and vegetable oil) during pregnancy may accelerate allergic diseases in infants.