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A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.
Michelini, S, Balakrishnan, B, Parolo, S, Matone, A, Mullaney, JA, Young, W, Gasser, O, Wall, C, Priami, C, Lombardo, R, et al
Microbiome. 2018;(1):171
Abstract
BACKGROUND Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space. RESULTS Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial ( http://www.nourishtoflourish.auckland.ac.nz/ ). CONCLUSIONS In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.
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The impact of vitamin A supplementation on the immune system of vitamin A-deficient children.
de Azevedo Paiva, A, Rondó, PH, Rehder Vaz-de-Lima, L, de Freitas Oliveira, C, Ueda, M, Gonçalves-Carvalho, C, Reinaldo, LG
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2010;(3):188-96
Abstract
BACKGROUND & AIMS To investigate the effect of vitamin A supplementation on parameters of the immune system of vitamin A-deficient children. METHODS The study was carried out in four phases: 1) determination of serum retinol in 631 children from 36 to 83 months of age; 2) assessment of immunological markers [immunoglobulins and complement fractions, immunophenotyping of T and B lymphocytes, and natural killer (NK) cells], blood count, and serum ferritin of 52 vitamin A-deficient children (serum retinol < 0.70 micromol/L); 3) supplementation of the 52 deficient children with 200,000 IU of vitamin A; 4) determination of serum retinol and the immunological parameters 2 months after vitamin A supplementation. RESULTS before vitamin A supplementation, 24.0 % of the children were anemic and 4.3 %had reduced ferritin concentrations. There was no significant difference between mean values of retinol according to the presence/absence of anemia. The mean values of the humoral and cellular immunological parameters did not show a statistically significant difference before and after supplementation with vitamin A. Children with concomitant hypovitaminosis A and anemia presented a significant increase in absolute CD4 and CD8 T-cell counts after vitamin A supplementation (p < 0.05). CONCLUSION vitamin A had an effect on the recruitment of T and B lymphocytes to the circulation of children with hypovitaminosis A and anemia.
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The interplay between socio-demographic variables, nutritional and immune status of HIV-positive/AIDS patients.
Oguntibeju, OO, van den Heever, WM, Van Schalkwyk, FE
Pakistan journal of biological sciences : PJBS. 2007;(20):3592-8
Abstract
This study examined the association between socio-demographic factors (educational level and employment status) and the nutritional and immune status of 35 HIV-positive/AIDS patients at baseline. Assessment of selected macro-and micronutrient dietary intake was done using a validated food frequency questionnaire. Evaluation of anthropometric profiles (body mass index, waist-hip ratio and percentage of body fat) was also evaluated. A questionnaire was applied to obtain information on the educational level and employment status of the patients. The CD4+ T-cell counts and viral loads of the same patients were determined using the flow cytometry and Polymerase Chain Reaction (PCR) method respectively. An association between educational level and dietary intake was significant (p < 0.05) for total dietary fibre, selenium and vitamin C. There was no significant (p > 0.05) association between the two socio-demographic variables (education and employment) and anthropometric profiles. The association between education, employment and CD4+ T-cell count was not significant (p > 0.05). The viral load showed a significant (p < 0.05) association with employment status but not correlated with education. The sample size or certain inherent biological and social factors probably affected the outcomes of the interplay between the two selected socio-demographic factors and the nutritional and immune status. It is suggested that the results of this study should be interpreted with caution. Further studies with larger sample sizes are recommended.
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The influence of oxygenated water on the immune status, liver enzymes, and the generation of oxygen radicals: a prospective, randomised, blinded clinical study.
Gruber, R, Axmann, S, Schoenberg, MH
Clinical nutrition (Edinburgh, Scotland). 2005;(3):407-14
Abstract
BACKGROUND & AIMS Oxygenated water with an oxygen concentration of 30-120 mg/l water is believed to improve the immune status, without any toxicological effects. The purpose of this clinical study was to assess the effects of long-term drinking of oxygenated water on the immune status. METHODS In this prospective, double-blinded, randomised study 24 volunteers of either sex (age 18-63 years) drank daily 3 times 500 ml either oxygenated (Verum-group: n=12) or normal mineral water (Placebo-group: n=12) for 28 days. On day 1 and day 28 standard laboratory tests, IgG, IgA and IgM, lymphocyte subpopulations and functional analysis of T-cells by flow cytometry, were done. Furthermore, the oxygen radicals were determined by the detection of the ascorbyl radicals. RESULTS Drinking of normal or oxygenated water had no effect on whole blood count or the liver enzymes. Interestingly the volunteers in the Verum-group showed a significant increase in ascorbyl radicals after drinking oxygenated water for 14 and 21 days. CD4+ and CD4+CD45RA+ lymphocytes as well as lymphocyte activation marker (CD69) and soluble IL-2 receptor increased in both groups, in contrast T-helper2 cells and IgG decreased during the study. The only differences between the two groups were a significant decrease of NK-cells form 13.42%+ or -5.04 to 10.83%+ or -4.82 (P<.002) and an increase of the Th1/Th2-ratio from 2.77%+ or -1.07 to 6.68%+ or -5.33 (P<.03) in the Verum-group. CONCLUSION Long-term consumption of oxygenated water has no apparent harmful effect on the liver, blood and the immune system. Moreover it leads to a transient moderate increase of oxygen radicals in the blood. An interesting observation is the increase of the Th1/Th2-ratio in the Verum group, whereas in both groups T-cell activation after mitogen stimulation, the soluble IL-2 receptor, the CD4+ and the naive CD4+CD45RA+ cells increased.
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Immuno-endocrine and metabolic responses to long distance ski racing in world-class male and female cross-country skiers.
Rønsen, O, Børsheim, E, Bahr, R, Klarlund Pedersen, B, Haug, E, Kjeldsen-Kragh, J, Høstmark, AT
Scandinavian journal of medicine & science in sports. 2004;(1):39-48
Abstract
The purpose of this study was to characterize the extent of immune, endocrine, substrate and metabolic changes during a long-distance cross-country ski race in extremely well-trained athletes and evaluate if the blood perturbations would indicate signs of health risk. Ten male (M) and six female (F) national team skiers were investigated as they followed their usual routines of race preparations. Blood samples were drawn before and immediately after a World Cup 50-km M and 30-km F ski race with a mean finish time of 142 and 104 min, respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged for both M and F. Serum testosterone remained unchanged in M, but doubled in F. Significant increases were observed in concentrations of granulocytes (F: 5 x, M: 5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x), noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5 x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in several immuno-endocrine, substrate and metabolic measurements after long distance cross-country ski racing and suggest that some of these marked changes may reflect the large amount of muscle mass involved during skiing.
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Nutritional support with nucleotide addition favors immune response in severely malnourished infants.
Vásquez-Garibay, E, Méndez-Estrada, C, Romero-Velarde, E, García-Iglesias, MT, Campollo-Rivas, O
Archives of medical research. 2004;(4):284-8
Abstract
BACKGROUND Adequate nutritional support of severe primary protein energy malnutrition (PEM) is indispensable for achieving normal immune response. However, an ideal dietetic criterion has not yet been established or accepted by the majority of health professionals caring for malnourished infants. Our objective was to demonstrate improvement in immune response in infants with PEM who received starting infant formula with nucleotides. METHODS Twelve malnourished infants 3-18 months of age were included in our study and were fed through a nasogastric tube with infant formula (3.35 kJ/mL) for 2 weeks and ad libitum for an additional 2 weeks. Anthropometric measurements and immunologic indicators such as phagocytosis, microbicidal activity, chemotaxis, and cell proliferation index were determined. The sample was divided into two groups; group 1 (n=6) was fed formula with nucleotides added, while group 2 (n=6) was fed a formula with no nucleotides. Paired t test was used to determine differences between initial and final results for each group for comparison between group 1 vs. group 2; a nonparametric Mann-Whitney U test was used for immunologic indicators. RESULTS Comparison of immunologic indicators showed no significant difference between groups. Groups 1 and 2 showed improvement in phagocytosis and microbicidal activity (p <0.05) and group 2 additionally showed improvement in cell proliferation index. CONCLUSIONS Infant formula with intake of 837 kJ/kg/d (200 kcal/kg/d) and proteins of 4 g/kg/d in infants with PEM had a favorable impact on immunologic indicators regardless of addition of nucleotides.
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Effects of supplementing a low-carotenoid diet with a tomato extract for 2 weeks on endogenous levels of DNA single strand breaks and immune functions in healthy non-smokers and smokers.
Briviba, K, Kulling, SE, Möseneder, J, Watzl, B, Rechkemmer, G, Bub, A
Carcinogenesis. 2004;(12):2373-8
Abstract
Increased consumption of tomato products is associated with a decreased risk of cancer. The present study was performed to investigate whether consumption of a tomato oleoresin extract for 2 weeks can affect endogenous levels of DNA single strand breaks in peripheral blood lymphocytes in healthy non-smokers and smokers. We also assessed, the effect of the tomato oleoresin extract on various immunological functions of peripheral blood mononuclear cells. A double-blinded, randomized, placebo-controlled study design was used. Over a period of 2 weeks 15 non-smokers and 12 smokers were given three tomato oleoresin extract capsules daily (each containing 4.88 mg lycopene, 0.48 mg phytoene, 0.44 mg phytofluene and 1.181 mg alpha-tocopherol). The control group received placebos. The baseline level of endogenous DNA damage for non-smokers was slightly (13%) and non-significantly (P = 0.44) lower than that of smokers. Placebo supplementation of non-smokers and smokers for 2 weeks did not significantly affect lycopene plasma levels or DNA damage in either group. Intervention with tomato oleoresin extract resulted in significant increases in total plasma lycopene and resulted in decreased levels of DNA strand breaks of approximately 32 (non-smokers) and 39% (smokers). However, this effect was not statistically significant in either group (P = 0.09 for non-smokers and P = 0.12 for smokers). Analysis of the distribution pattern of DNA strand breaks showed a statistically significant (P < 0.05) increase in the number of comets in class 0 (undamaged) and a decrease in classes 1 and 2 (damaged) after the tomato oleoresin extract intervention in non-smokers. The changes in the smoker group were not statistically significant. Treatment with the tomato extract had no effect on lymphocyte proliferation, NK cell activity, interleukin (IL)-2 production and tumor necrosis factor (TNF)alpha production, but it significantly reduced IL-4 production in smokers (P = 0.009).
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Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men.
Turnlund, JR, Jacob, RA, Keen, CL, Strain, JJ, Kelley, DS, Domek, JM, Keyes, WR, Ensunsa, JL, Lykkesfeldt, J, Coulter, J
The American journal of clinical nutrition. 2004;(6):1037-44
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Abstract
BACKGROUND Short-term high copper intake does not appear to affect indexes of copper status or functions related to copper status, but the effects of long-term high copper intake are unknown. OBJECTIVE A study was conducted in men to determine the effect of long-term high copper intake on indexes of copper status, oxidant damage, and immune function. DESIGN Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing an average of 1.6 mg Cu/d. The men continued the study under free-living conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men then returned to the MRU for 18 d of the same diet as during the first period, except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity, ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity, erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary thiobarbituric acid-reactive substances were measured during each MRU period. RESULTS Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase were significantly higher at the end of the second MRU period than at the end of the first. Urinary copper excretion, hair copper concentrations, and urinary thiobarbituric acid-reactive substances were significantly higher during the second MRU period than during the first. Polymorphonuclear cell count, the percentage of white blood cells, lymphocyte count, and interleukin 2R were affected by copper supplementation. Antibody titer for the Beijing strain of influenza virus was significantly lower in supplemented subjects after immunization than in unsupplemented control subjects. CONCLUSIONS Under highly controlled conditions, long-term high copper intake results in increases in some indexes of copper status, alters an index of oxidant stress, and affects several indexes of immune function. The physiologic implications of these changes are unknown.
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Vitamin E and immunity after the Kona Triathlon World Championship.
Nieman, DC, Henson, DA, McAnulty, SR, McAnulty, LS, Morrow, JD, Ahmed, A, Heward, CB
Medicine and science in sports and exercise. 2004;(8):1328-35
Abstract
PURPOSE To measure the influence of vitamin E ingestion on oxidative stress and immune changes in response to the Triathlon World Championship in Kona, Hawaii. METHODS Thirty-eight triathletes received vitamin E (VitE) (800 IU x d(-1) alpha-tocopherol) or placebo (Pla) capsules in randomized, double-blind fashion for 2 months before the race event. Blood, urine, and saliva samples were collected the day before the race, 5-10 min postrace, and 1.5 h postrace. RESULTS Race times did not differ between VitE (N = 19, 721 +/- 24 min) and Pla groups (N = 17, 719 +/- 27 min, P = 0.959), and both groups maintained an intensity of approximately 80% maximum heart rate during the bike and run portions. Plasma alpha-tocopherol was approximately 75% higher in the VitE versus Pla group prerace (24.1 +/- 1.1 and 13.8 +/- 1.1 micromol x L(-1), P < 0.001, respectively) and postrace. Plasma F2-isoprostanes increased 181% versus 97% postrace in the VitE versus Pla groups (P = 0.044). IL-6 was 89% higher (166 +/- 28 and 88 +/- 13 pg x mL(-1), respectively, P = 0.016), IL-1ra was 107% higher (4848 +/- 1203 and 2341 +/- 790 pg x mL(-1), respectively, P = 0.057), and IL-8 was 41% higher postrace in the VitE versus Pla groups (26.0 +/- 3.6 and 18.4 +/- 2.4 pg x mL(-1), respectively, P = 0.094). CONCLUSION These data indicate that vitamin E (800 IU x d(-1) for 2 months) compared with placebo ingestion before a competitive triathlon race event promotes lipid peroxidation and inflammation during exercise.
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L-ornithine alpha-ketoglutarate in HIV infection: effects on muscle, gastrointestinal, and immune functions.
Karsegard, VL, Raguso, CA, Genton, L, Hirschel, B, Pichard, C
Nutrition (Burbank, Los Angeles County, Calif.). 2004;(6):515-20
Abstract
OBJECTIVES There have been claims that l-ornithine alpha-ketoglutarate (OKG) exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed at quantifying the effects of OKG on muscle force, body composition, and immune function in outpatients infected with the human immunodeficiency virus (HIV) and presenting weight loss. METHODS Forty-six HIV(+) patients were included in a double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG or isonitrogenous placebo and nutritional counseling). Podometry, handgrip strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance, 3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk. RESULTS At baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/- 172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10) copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808 kcal/d). Twenty-nine patients completed the protocol. Both groups increased their body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P < 0.01 versus baseline). They showed a similar positive correlation between handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No other differences were observed between groups. CONCLUSIONS All patients increased their body mass index and triceps skinfold thickness due to food supplementation and diet counseling. Oral OKG failed to improve nutritional, functional, or immunologic status in these weight-losing HIV(+) patients and had important gastrointestinal side effects.