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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.
2.
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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Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon.
Nieman, DC, Henson, DA, McAnulty, SR, McAnulty, L, Swick, NS, Utter, AC, Vinci, DM, Opiela, SJ, Morrow, JD
Journal of applied physiology (Bethesda, Md. : 1985). 2002;(5):1970-7
Abstract
The purpose of this randomized study was to measure the influence of vitamin C (n = 15 runners) compared with placebo (n = 13 runners) supplementation on oxidative and immune changes in runners competing in an ultramarathon race. During the 7-day period before the race and on race day, subjects ingested in randomized, double-blind fashion 1,500 mg/day vitamin C or placebo. On race day, blood samples were collected 1 h before race, after 32 km of running, and then again immediately after race. Subjects in both groups maintained an intensity of approximately 75% maximal heart rate throughout the ultramarathon race and ran a mean of 69 km (range: 48-80 km) in 9.8 h (range: 5-12 h). Plasma ascorbic acid was markedly higher in the vitamin C compared with placebo group prerace and rose more strongly in the vitamin C group during the race (postrace: 3.21 +/- 0.29 and 1.28 +/- 0.12 microg/100 microl, respectively, P < 0.001). No significant group or interaction effects were measured for lipid hydroperoxide, F2-isoprostane, immune cell counts, plasma interleukin (IL)-6, IL-10, IL-1-receptor antagonist, or IL-8 concentrations, or mitogen-stimulated lymphocyte proliferation and IL-2 and IFN-gamma production. These data indicate that vitamin C supplementation in carbohydrate-fed runners does not serve as a countermeasure to oxidative and immune changes during or after a competitive ultramarathon race.