Dietary supplementation with Bifidobacterium lactis NCC2818 from weaning reduces local immunoglobulin production in lymphoid-associated tissues but increases systemic antibodies in healthy neonates

Weaning is associated with a major shift in the microbial community of the intestine, and this instability may make it more acquiescent than the adult microbiota to long-term changes. Modulation achieved through dietary interventions may have potentially beneficial effects on the developing immune system, which is driven primarily by the microbiota. The specific aim of the present study was to determine whether immune development could be modified by dietary supplementation with the human probiotic Bifidobacterium lactis NCC2818 in a tractable model of weaning in infants. Piglets were reared by their mothers before being weaned onto a solid diet supplemented with B. lactis NCC2818, while sibling controls did not receive supplementation. Probiotic supplementation resulted in a reduction in IgA (P,0·0005) and IgM (P,0·009) production by mucosal tissues but had no effect on IgG production (P.0·05). Probiotic- supplemented pigs had more mast cells than unsupplemented littermates (P,0·0001), although numbers in both groups were low. In addition, the supplemented piglets made stronger serum IgG responses to fed and injected antigens (P,0·05). The present findings are consistent with B. lactis NCC2818 reducing intestinal permeability induced by weaning, and suggest that the piglet is a valuable intermediate between rodent models and human infants. The results also strongly suggest that measures of the effect of probiotic supplementation on the immune system need to be interpreted carefully as proxy measures of health benefit. However, they are useful in developing an understanding of the mechanism of action of probiotic strains, an important factor in predicting favourable health outcomes of nutritional intervention.

Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818

Background: The process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals. Objective: To use a new systems approach to provide an overview of host metabolism and the developing immune system in response to nutritional intervention around the weaning period. Design: Piglets (n¼14) were weaned onto either an eggbased or soya-based diet at 3 weeks until 7 weeks, when all piglets were switched onto a fish-based diet. Half the animals on each weaning diet received Bifidobacterium lactis NCC2818 supplementation from weaning onwards. Immunoglobulin production from immunologically relevant intestinal sites was quantified and the urinary 1H NMR metabolic profile was obtained from each animal at post mortem (11 weeks). Results: Different weaning diets induced divergent and sustained shifts in the metabolic phenotype, which resulted in the alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary standardisation. B lactis NCC2818 supplementation affected the systemic metabolism of the different weaning diet groups over and above the effects of diet. Additionally, production of gut mucosa-associated IgA and IgM was found to depend upon the weaning diet and on B lactis NCC2818 supplementation. Conclusion: The correlation of urinary 1H NMR metabolic profile with mucosal immunoglobulin production was demonstrated, thus confirming the value of this multiplatform approach in uncovering non-invasive biomarkers of immunity. This has clear potential for translation into human healthcare with the development of urine testing as a means of assessing mucosal immune status. This might lead to early diagnosis of intestinal dysbiosis and with subsequent intervention, arrest disease development. This system enhances our overall understanding of pathologies under supra-organismal control.

Effect of inclusion of lactulose and Lactobacillus plantarum on the intestinal environment and performance of piglets at weaning

The prebiotic lactulose, a probiotic strain of Lactobacillus plantarum (L. plantarum) and a synbiotic combination of these two agents were evaluated as growth promoters in 25–39-day old commercial weaning pigs. Ninety-six weaning pigs were allocated into 32 pens, taking initial weight into account, and distributed into four groups as follows: a control diet (CTR), the same diet supplemented daily with L. plantarum (109 CFU/mL sprayed on top; 20 mL/pig) (LPN); 10 g/kg lactulose (LAC) or a combination of both treatments (SYN). At day 14, eight piglets from each group were euthanized and proximal colon digesta was sampled for luminal pH, short-chain fatty acids (SCFA) and lactic acid concentrations. Deoxyribonucleic acid was extracted from colonic digesta and the microbial community was profiled by terminal restriction fragment length polymorphism analysis (T-RFLP) and qPCR. Blood urea nitrogen (BUN) and acute-phase proteins (Pig-MAP) were measured. Lactulose treatment (LAC) improved feed intake (P<0.05), average daily gain (P<0.01), feed:gain ratio (P<0.05) and reduced BUN (P<0.01). Both, LAC and LPN treatment, decreased the Enterobacteriaceae:Lactobacillus spp. ratio in the colonic luminal contents (P<0.05). Moreover LPN treatment promoted a decrease in the percentage of branched fatty acids (P<0.01) suggesting a reduction in proteolytic microbial activity. Microbial profiling of colonic luminal contents by T-RFLP revealed changes in some microbial species. Terminal restriction fragments (TRFs) compatible with Bifidobacterium thermoacidophilum were more frequently detected in experimental diets compared to CTR (P<0.05). Pigs receiving SYN diet demonstrated the combined positive effects of individual LAC and LPN treatment although we were not able to show a specific increase in the probiotic strain with the inclusion of lactulose. Collectively, these data suggest the combination of lactulose and L. plantarum acts as a complementary synbiotic, but not as a synergistic combination.

Dietary iron depletion at weaning imprints low microbiome diversity and this is not recovered with oral nano Fe(III)

Alterations in the gut microbiota have been recently linked to oral iron. We conducted two feeding studies including an initial diet-induced iron-depletion period followed by supplementation with nanoparticulate tartrate-modified ferrihydrite (Nano Fe(III): considered bioavailable to host but not bacteria) or soluble ferrous sulfate (FeSO4: considered bioavailable to both host and bacteria). We applied denaturing gradient gel electrophoresis and fluorescence in situ hybridization for study-1 and 454-pyrosequencing of fecal 16S rRNA in study-2. In study-1, the within-community microbial diversity increased with FeSO4 (P = 0.0009) but not with Nano Fe(III) supplementation. This was confirmed in study-2, where we also showed that iron depletion at weaning imprinted significantly lower within- and between-community microbial diversity compared to mice weaned onto the iron-sufficient reference diet (P < 0.0001). Subsequent supplementation with FeSO4 partially restored the within-community diversity (P = 0.006 in relation to the continuously iron-depleted group) but not the between-community diversity, whereas Nano Fe(III) had no effect. We conclude that (1) dietary iron depletion at weaning imprints low diversity in the microbiota that is not, subsequently, easily recovered; (2) in the absence of gastrointestinal disease iron supplementation does not negatively impact the microbiota; and (3) Nano Fe(III) is less available to the gut microbiota.

Maternal weaning modulates emotional behavior and regulates the gut-brain axis

Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria.

Early weaning accelerates the differentiation of mucous neck cells in rat gastric mucosa: Possible role of TGF alpha/EGFR

The development of the gastric mucosa is controlled by hormones, growth factors and feeding behavior. Early weaning (EW), which means the abrupt interruption of suckling, increases proliferation and differentiation in the rat gastric epithelium. Transforming growth factor alpha(TGF alpha) is secreted in the stomach, binds to the epidermal growth factor receptor( EGFR) and may control cell proliferation, differentiation and migration. Here, we investigated the influence of suckling-weaning transition on the differentiation of mucous neck cells in the stomach and its association to the expression of TGF alpha and EGFR. Fifteen-day-old Wistar rats were divided into two groups: suckling( control), in which pups were kept with the dam, and early weaning( EW), in which rats were separated from their mother and fed with hydrated powdered chow. TGF alpha and EGFR levels were increased at 18 days in EW animals compared to control ones (p<0.05). Histochemical reactions with Periodic Acid-Schiff reagent+Alcian Blue or Bandeiraea simplicifolia II lectin were used to stain the mucous neck cells and showed an increase in this cell population throughout EW, which was more pronounced at 17 days when compared to suckling pups (p<0.05). These morphological results were confirmed by RT-PCR for mucin 6. The levels of mucin 6 mRNA were higher in EW animals from the 16th to the 18th day(1-3 days post-weaning) when compared to the respective control group. Inhibition of EGFR through AG1478 administration to EW animals prevented the expansion of mucous neck cell population induced by EW (p<0.05). Therefore, early weaning up regulated TGF alpha/EGFR expression and induced differentiation of mucous neck cells. Moreover, we showed that EGFR takes part in the maturation of this cell population. We conclude that regular suckling-weaning transition is crucial to guarantee the development of the gastric mucosa. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

Genotype-environment interaction for post-weaning traits in Nellore beef cattle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparison of selection criteria for pre-weaning growth traits of Nelore cattle

Genetic parameters were estimated for pre-weaning average daily gain (ADG) and number of days to gain 160 kg from birth to weaning (D 160) of Nelore cattle. Ranks of animals were compared for these traits. Heritability estimates were 0.17 and 0.10 for ADG (direct and maternal), and 0.14 and 0.09, for D 160 (direct and maternal). Rank correlations between expected breeding values (EBV) were 0.97 and 0.95, for direct and maternal effects, respectively. Despite similar heritability estimates and high rank correlations, results showed that changes in rank could happen when choosing the best animals according to EBV for D 160 or ADG. There were evidences that sires selected using D 160 would produce progeny that achieve a specified market weight at an earlier age and would be more uniform, since this criterion is calculated as a harmonic mean function. (C) 2003 Elsevier B.V. All rights reserved.

Results of 23 years of selection for post-weaning weight in a Caracu beef herd

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genotype by environment interaction for birth and weaning weights of composite beef cattle in different regions of Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of relations among age at first calving, average weight gains and weights from weaning to maturity in Nellore cattle

Dados de 23.120 animais da raça Nelore foram utilizados para estimar herdabilidade e correlações genéticas para a idade ao primeiro parto, o ganho em peso da desmama ao ano e do ano ao sobreano, o peso à desmama, o peso ao ano, o peso ao sobreano e os pesos aos 2 e aos 5 anos de idade. Utilizou-se o método da máxima verossimilhança restrita, em análise multicaracterística. As herdabilidades estimadas para idade ao primeiro parto, ganho da desmama ao ano, ganho do ano ao sobreano, peso à desmama, peso ao ano, peso ao sobreano e peso aos 2 aos 5 anos foram de 0,17 ± 0,01; 0,23 ± 0,03; 0,25 ± 0,03; 0,28 ± 0,02; 0,26 ± 0,03; 0,30 ± 0,03; 0,32 ± 0,02 e 0,36 ± 0,04, respectivamente. Correlações genéticas baixas e negativas foram estimadas entre a idade ao primeiro parto e os pesos medidos em diferentes idades, que variaram de -0,26 a -0,14. As correlações genéticas estimadas entre a idade ao primeiro parto e os ganhos de peso também foram negativas, porém levemente superiores (-0,29 e -0,32). Os resultados indicam que a seleção para maior ganho de peso pode reduzir a idade ao primeiro parto e aumentar o peso adulto de fêmeas da raça Nelore. Mudança genética mais rápida para diminuição da idade ao primeiro parto das fêmeas pode ser obtida com a inclusão dessa característica nos índices de seleção.

Environmental and genetic factors affecting the weaning-estrus interval in sows

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Early administration of inhaled nitric oxide to children with acute respiratory distress syndrome and its effects on oxygenation and ventilator settings: prospective preliminary report of ten patients

Aim. To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to assess its acute and sustained effects on oxygenation and ventilator settings.Patients and Methods. Ten children with ARDS, aged 1 to 132 months (median, 11 months), with arterial saturation of oxygen <88% while receiving a fraction of inspired oxygen (FiO(2)) 0.6 and a positive end-expiratory pressure of greater than or equal to 10 cm H2O were included in the study. The acute response to iNO was assessed in a 4-hour dose-response test, and positive response was defined as an increase in the PaO2/FiO(2) ratio of 10 mmHg above baseline values. Conventional therapy was not changed during the test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO(2), oxygenation index, gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules.Results. At the end of the 4-hour test, all the children showed significant improvement in the PaO2/FiO(2) ratio (63.6%) and the oxygenation index (44.9%) compared with the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FiO(2) and peak inspiratory pressure could be quickly and significantly reduced., No toxicity from methemoglobin or nitrogen dioxide was observed.Conclusion. Administration of iNO to children is safe. iNO causes rapid and sustained improvement in oxygenation without adverse effects. Ventilator settings can safely be reduced during iNO treatment.

Intravaginal progesterone device and/or temporary weaning on reproductive performance of anestrous crossbred Angus x Nelore cows

The objective of this experiment was to evaluate effects of treatments with intravaginal progesterone (N) device and/or 48 h temporary weaning (TW) on reproductive performance of postpartum anestrous crossbred Angus x Nelore cows, throughout the breeding season (BS). Anestrous cows (n = 296; 53 5 DPP, body condition score between 2.5 and 3.5, on a 1-5 scale) were assigned randomly to four treatments (2 x 2 factorial design): (1) Control Group (no treatment; n = 73); (2) TW Group (48 h TW beginning on day 0 of BS; n = 70); (3) P4 Group (Intravaginal P4 device between days -7 and 0 of BS; n = 73); and (4) P4+TW Group (Intravaginal P4 device between days -7 and 0 of BS followed by 48h TW; n=70). on day 0 of BS (when P4 devices were removed and TW was initiated), cows had their ovaries evaluated by ultrasonography aiming to evaluate size of the largest follicle. Signs of behavioral estrus were observed twice a day (morning and evening), between days 0 and 25 of BS, and cows observed in estrus were inseminated 12 h later. Between days 26 and 80 of BS, cows were submitted to natural service. Pregnancy diagnosis was conducted by transrectal ultrasonography on days 32 and 53 (pregnancies by AI) and 114 (pregnancies by natural service). Rates of detection of estrus during the first 3 days and within 25 days of BS were greater in cows receiving TW (45.0% compared with 9.6% and 50.0% compared with 29.5%, respectively; P < 0.01). Conception rate in cows inseminated in the first 3 days of BS was greater in cows treated with P4 (54.8% compared with 11.1 %; P < 0.01). Combining P4+TW increased pregnancy rate in the first 3 days (Control: 1.4%, TW: 4.3%, P4: 8.2% and P4+TW: 24.3%; P < 0.01) and in 25 days of BS (Control: 10.9%, TW: 7.1%, P4: 13.7% and P4+TW: 28.6%; P < 0.05). Pregnancy rate at the end of BS did not differ among treatment groups. In conclusion, TW alone increased estrous behavior whereas P4 alone benefited conception. Combining P4 with TW improved pregnancy rate with direct benefits to behavioral estrus and conception. (c) 2008 Elsevier B.V. All rights reserved.