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Perinatal nutrition programs physiologic and metabolic functions, with consequences on the susceptibility to develop metabolic diseases in adulthood. The microbiota represents a key factor of such programming. We investigated whether perinatal prebiotic [short-chain fructooligosaccharides (scFOS)] supplementation improved adult metabolic health in association with microbiota changes in pigs used as human model. Sows were supplemented with scFOS or not during the end of gestation and the entire lactation, and offspring received scFOS accordingly during 1 mo after weaning. Pigs were then fed a standard diet for 5 mo, followed by a high-fat diet for 3 mo once adults. Perinatal scFOS supplementation induced a persistent modulation of the composition of the fecal microbiota in adulthood, notably by increasing the Prevotella genus. Meanwhile, scFOS animals displayed improved capacity to secrete glucagon-like peptide-1 and improved pancreas sensitivity to glucose without any changes in peripheral insulin sensitivity. Perinatal scFOS supplementation also increased ileal secretory IgA secretion and alkaline phosphatase activity and decreased TNF-α expression in adipose tissue. In conclusion, perinatal scFOS supplementation induced long-lasting modulation of intestinal microbiota and had beneficial consequences on the host physiology in adulthood. Our results highlight the key role of perinatal nutrition on later microbiota and host metabolic adaptation to an unbalanced diet.-Le Bourgot, C., Ferret-Bernard, S., Apper, E., Taminiau, B., Cahu, A., Le Normand, L., Respondek, F., Le Huërou-Luron, I., Blat, S. Perinatal short-chain fructooligosaccharides program intestinal microbiota and improve enteroinsular axis function and inflammatory status in high-fat diet-fed adult pigs.
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Ração Animal/análise , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/veterinária , Enteropatias/veterinária , Oligossacarídeos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Suplementos Nutricionais , Fezes/microbiologia , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Inflamação/tratamento farmacológico , Inflamação/etiologia , Insulina/metabolismo , Enteropatias/tratamento farmacológico , Enteropatias/etiologia , Gravidez , Suínos , Doenças dos Suínos/etiologiaRESUMO
This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.
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A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.
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Cognição/fisiologia , Dieta Ocidental , Hipocampo/metabolismo , Lactação/fisiologia , Lipídeos/sangue , Microbiota/fisiologia , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Animais Lactentes , Suplementos Nutricionais , Feminino , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Leite/metabolismo , SuínosRESUMO
Prebiotic supplementation modulates immune system development and function. However, less is known about the effects of maternal prebiotic consumption on offspring intestinal defences and immune system responsiveness. We investigated the effects of maternal short-chain fructo-oligosaccharide (scFOS) supplementation on mucin-secreting cells, ileal secretory IgA and cytokine secretion of weaned offspring and their humoral response to an oral vaccine against obligate intracellular Lawsonia intracellularis. Sows were fed a control diet (CTRL) or scFOS-supplemented diet during the last third of gestation and throughout lactation. At weaning, each litter was divided into two groups receiving a post-weaning CTRL or scFOS diet for a month. Pigs from the four groups were either non-vaccinated (n 16) or vaccinated (n 117) at day 33. Biomarkers related to intestinal defences and immune parameters were analysed 3 weeks later. SCFA production was assessed over time in suckling and weaned pigs. Maternal scFOS supplementation improved ileal cytokine secretions (interferon (IFN)-γ, P<0·05; IL-4, P=0·07) and tended to increase caecal goblet cell number (P=0·06). It increased IgA vaccine response in the serum (P<0·01) and ileal mucosa (P=0·08). Higher bacterial fermentative activity was observed during lactation (total faecal SCFA, P<0·001) and after weaning (colonic butyrate, P=0·10) in pigs from scFOS-supplemented mothers. No synergistic effect between maternal and post-weaning scFOS supplementation was observed. Therefore, maternal scFOS supplementation has long-lasting consequences by strengthening gut defences and immune response to a vaccine against an intestinal obligate intracellular pathogen. Prebiotic consumption by gestating and lactating mothers is decisive in modulating offspring intestinal immunity.
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Vacinas Bacterianas/imunologia , Butiratos/sangue , Citocinas/metabolismo , Células Caliciformes/fisiologia , Lawsonia (Bactéria) , Oligossacarídeos/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citocinas/genética , Infecções por Desulfovibrionaceae/microbiologia , Infecções por Desulfovibrionaceae/veterinária , Dieta/veterinária , Suplementos Nutricionais , Feminino , Fenômenos Fisiológicos da Nutrição Materna , Oligossacarídeos/química , Prebióticos , Suínos , Doenças dos Suínos/prevenção & controleRESUMO
Breast milk composition is influenced by maternal diet. This study aimed to evaluate if supplementation of maternal diet with a prebiotic fibre, through its potential effect on milk composition, can be a leverage to orientate the gut microbiota of infants in a way that would be beneficial for their health. Twelve sows received a diet supplemented with short chain fructo-oligosaccharides or maltodextrins during the last month of gestation and the lactation. Oligosaccharidic and lipidomic profiles of colostrum and mature milk (21 days), as well as faecal microbiota composition and metabolomic profile of 21 day-old piglets were evaluated. The total porcine milk oligosaccharide concentration tended to be lower in scFOS-supplemented sows, mainly due to the significant reduction of the neutral core oligosaccharides (in particular that of a tetrahexose). Maternal scFOS supplementation affected the concentration of 31 lipids (mainly long-chain triglycerides) in mature milk. Faecal short-chain fatty acid content and that of 16 bacterial metabolites were modified by scFOS supplementation. Interestingly, the integrative data analysis gave a novel insight into the relationships between (i) maternal milk lipids and PMOs and (ii) offspring faecal bacteria and metabolites. In conclusion, scFOS-enriched maternal diet affected the composition of mature milk, and this was associated with a change in the colonisation of the offspring intestinal microbiota.
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Lactação , Leite , Animais , Suínos , Gravidez , Feminino , Humanos , Leite/metabolismo , Projetos Piloto , Suplementos Nutricionais/análise , Dieta/veterinária , Metaboloma , Oligossacarídeos/metabolismo , Lipídeos , Ração Animal/análiseRESUMO
The human milk (HM) microbiota, a highly diverse microbial ecosystem, is thought to contribute to the health benefits associated with breast-feeding, notably through its impact on infant gut microbiota. Our objective was to further explore the role of HM bacteria on gut homeostasis through a "disassembly/reassembly" strategy. HM strains covering the diversity of HM cultivable microbiota were first characterized individually and then assembled in synthetic bacterial communities (SynComs) using two human cellular models, peripheral blood mononuclear cells and a quadricellular model mimicking intestinal epithelium. Selected HM bacteria displayed a large range of immunomodulatory properties and had variable effects on epithelial barrier, allowing their classification in functional groups. This multispecies characterization of HM bacteria showed no clear association between taxonomy and HM bacteria impacts on epithelial immune and barrier functions, revealing the entirety and complexity of HM bacteria potential. More importantly, the assembly of HM strains into two SynComs of similar taxonomic composition but with strains exhibiting distinct individual properties, resulted in contrasting impacts on the epithelium. These impacts of SynComs partially diverged from the predicted ones based on individual bacteria. Overall, our results indicate that the functional properties of the HM bacterial community rather than the taxonomic composition itself could play a crucial role in intestinal homeostasis of infants.
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BACKGROUND & AIMS: In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut-brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control. METHODS: An integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis. RESULTS: We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP. CONCLUSION: This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.
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Derivação Gástrica , Obesidade Mórbida , Humanos , Animais , Suínos , Derivação Gástrica/efeitos adversos , Porco Miniatura , Obesidade Mórbida/cirurgia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Obesidade/cirurgia , Obesidade/etiologia , Redução de Peso/fisiologia , Encéfalo/diagnóstico por imagem , RNA MensageiroRESUMO
Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula.
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Ração Animal/análise , Proteínas Alimentares/farmacologia , Insulina/metabolismo , Período Pós-Prandial/fisiologia , Suínos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Peso ao Nascer , Glicemia , Dieta/veterinária , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Homeostase , Secreção de Insulina , Pâncreas/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suínos/sangue , Regulação para CimaRESUMO
The ghrelin-ghrelin receptor (GHSR1) system is one of the most important mechanisms regulating food intake and energy balance. To be fully active, ghrelin is acylated with medium-chain fatty acids (MCFA) through the ghrelin-O-acetyl transferase (GOAT). Several studies reported an impact of dietary MCFA on ghrelin acylation in adults. Our study aimed at describing early post-natal development of the ghrelin system in mini-pigs as a model of human neonates and evaluating the impact of dietary MCFA. Suckled mini-pigs were sacrificed at post-natal day (PND) 0, 2, 5, and 10 or at adult stage. In parallel, other mini-pigs were fed from birth to PND10 a standard or a dairy lipid-enriched formula with increased MCFA concentration (DL-IF). Plasma ghrelin transiently peaked at PND2, with no variation of the acylated fraction except in adults where it was greater than during the neonatal period. Levels of mRNA coding pre-proghrelin (GHRL) and GOAT in the antrum did not vary during the post-natal period but dropped in adults. Levels of antral pcsk1/3 (cleaving GHRL into ghrelin) mRNA decreased significantly with age and was negatively correlated with plasma acylated, but not total, ghrelin. Hypothalamic ghsr1 mRNA did not vary in neonates but increased in adults. The DL-IF formula enriched antral tissue with MCFA but did not impact the ghrelin system. In conclusion, the ghrelin maturation enzyme PCSK1/3 gene expression exhibited post-natal modifications parallel to transient variations in circulating plasma ghrelin level in suckling piglets but dietary MCFA did not impact this post-natal development.
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The gut microbiota contributes to human health and disease; however, the mechanisms by which commensal bacteria interact with the host are still unclear. To date, a number of in vitro systems have been designed to investigate the host-microbe interactions. In most of the intestinal models, the enteroendocrine cells, considered as a potential link between gut bacteria and several human diseases, were missing. In the present study, we have generated a new model by adding enteroendocrine cells (ECC) of L-type (NCI-H716) to the one that we have previously described including enterocytes, mucus, and M cells. After 21 days of culture with the other cells, enteroendocrine-differentiated NCI-H716 cells showed neuropods at their basolateral side and expressed their specific genes encoding proglucagon (GCG) and chromogranin A (CHGA). We showed that this model could be stimulated by commensal bacteria playing a key role in health, Roseburia intestinalis and Bacteroides fragilis, but also by a pathogenic strain such as Salmonella Heidelberg. Moreover, using cell-free supernatants of B. fragilis and R. intestinalis, we have shown that R. intestinalis supernatant induced a significant increase in IL-8 and PYY but not in GCG gene expression, while B. fragilis had no impact. Our data indicated that R. intestinalis produced short chain fatty acids (SCFAs) such as butyrate whereas B. fragilis produced more propionate. However, these SCFAs were probably not the only metabolites implicated in PYY expression since butyrate alone had no effect. In conclusion, our new quadricellular model of gut epithelium could be an effective tool to highlight potential beneficial effects of bacteria or their metabolites, in order to develop new classes of probiotics.
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Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow's milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.
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The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a "window of opportunity" to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.
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Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.
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Breast milk is the gold standard in neonatal nutrition, but most infants are fed infant formulas in which lipids are usually of plant origin. The addition of dairy lipids and/or milk fat globule membrane extracts in formulas improves their composition with beneficial consequences on protein and lipid digestion. The probiotic Lactobacillus fermentum (Lf) was reported to reduce transit time in rat pups, which may also improve digestion. This study aimed to investigate the effects of the addition of dairy lipids in formulas, with or without Lf, on protein and lipid digestion and on gut physiology and metabolism. Piglets were suckled from postnatal days 2 to 28, with formulas containing either plant lipids (PL), a half-half mixture of plant and dairy lipids (DL), or this mixture supplemented with Lf (DL+Lf). At day 28, piglets were euthanized 90 min after their last feeding. Microstructure of digesta did not differ among formulas. Gastric proteolysis was increased (P < 0.01) in DL and DL+Lf (21.9 ± 2.1 and 22.6 ± 1.3%, respectively) compared with PL (17.3 ± 0.6%) and the residual proportion of gastric intact caseins decreased (p < 0.01) in DL+Lf (5.4 ± 2.5%) compared with PL and DL (10.6 ± 3.1% and 21.8 ± 6.8%, respectively). Peptide diversity in ileum and colon digesta was lower in PL compared to DL and DL+Lf. DL and DL+Lf displayed an increased (p < 0.01) proportion of diacylglycerol/cholesterol in jejunum and ileum digesta compared to PL and tended (p = 0.07) to have lower triglyceride/total lipid ratio in ileum DL+Lf (0.019 ± 0.003) as compared to PL (0.045 ± 0.011). The percentage of endocrine tissue and the number of islets in the pancreas were decreased (p < 0.05) in DL+Lf compared with DL. DL+Lf displayed a beneficial effect on host defenses [increased goblet cell density in jejunum (p < 0.05)] and a trophic effect [increased duodenal (p = 0.09) and jejunal (p < 0.05) weights]. Altogether, our results demonstrate that the addition of dairy lipids and probiotic Lf in infant formula modulated protein and lipid digestion, with consequences on lipid profile and with beneficial, although moderate, physiological effects.
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The health benefits of breast-feeding have been recognised for a long time. In particular, breast-feeding is associated with lower incidence of necrotising enterocolitis and diarrhoea during the early period of life and with lower incidence of inflammatory bowel diseases, type 2 diabetes and obesity later in life. The higher nutritional and protective degree of human milk is related to its nutritional composition that changes over the lactation period and to the biological activities of specific components while lower growth rate of breast-fed infants may be attributed to their self-regulation of milk intake at a lower level than formula-fed infants. Many results now suggest that the developmental changes in intestinal and pancreatic function that occur postnatally are modulated by the diet. Indeed, formula-feeding induces intestinal hypertrophy and accelerates maturation of hydrolysis capacities; it increases intestinal permeability and bacterial translocation, but does not induce evident differences in microbiota composition. Whether these changes would be beneficial for enhancing absorptive capacities and for educating the gut-associated immune system remains to be further studied. Moreover, it is evident that formula-feeding increases basal blood glucose and decreases plasma ketone body concentrations, while discrepancies on postprandial glycaemia, insulin and incretin responses in both human studies and experimental studies are inconclusive. Manipulating the composition of formula, by reducing protein content, adding prebiotics, growth factors or secretory IgA can modulate intestinal and pancreatic function development, and thereby may reduce the differential responses between breast-fed and formula-fed neonates. However, the developmental responses of the digestive tract to different feeding strategies must be elucidated in terms of sensitivity to developing diseases, taking into account the major role of the intestinal microbiota.
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Aleitamento Materno , Sistema Digestório , Nível de Saúde , Fórmulas Infantis , Animais , Glicemia/análise , Diabetes Mellitus Tipo 2/prevenção & controle , Diarreia/prevenção & controle , Sistema Digestório/crescimento & desenvolvimento , Enterocolite Necrosante/prevenção & controle , Feminino , Promoção da Saúde , Humanos , Lactente , Fórmulas Infantis/química , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/prevenção & controle , Intestinos/microbiologia , Intestinos/fisiologia , Corpos Cetônicos/sangue , Leite Humano/química , Valor Nutritivo , Obesidade/prevenção & controle , Pâncreas/fisiologia , Aumento de PesoRESUMO
INTRODUCTION: Obesity has become a pandaemic even in children. We aimed to investigate the impact of obesity in youth on later pancreatic intrinsic nervous system (PINS) phenotype and control of insulin secretion. METHODS: Young mice (5-week-old, T0 group) were fed either a normal diet (ND group) or a Western diet (WD group) for 12 weeks. Pancreas nervous system density, PINS phenotype and pancreas anatomy were analysed by immunohistochemistry at T0 and in adulthood (ND and WD groups). Insulin secretion was also studied in these 3 groups using a new model of ex vivo pancreatic culture, where PINS was stimulated by nicotinic and nitrergic agonists with and without antagonists. Insulin was assayed in supernatants by ELISA. RESULTS: Pancreas nervous system density decreased with age in ND (P < .01) but not in WD mice (P = .08). Western diet decreased the PINS nitrergic component as compared to normal diet (P < .01) but it did not modify its cholinergic component (P = .50). Nicotinic PINS stimulation induced greater insulin secretion in ND compared to WD mice (P < .001) whereas nitrergic stimulation significantly decreased insulin secretion in ND mice (P < .001) and tended to increase insulin secretion in WD mice (P = .08). Endocrine pancreas anatomy was not modified by the Western diet as compared to the normal diet (P = .93). CONCLUSIONS: Early Western diet induced neuronal density and phenotype changes in PINS that might be involved in the pancreas insulin secretion dysfunctions associated with obesity.
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Diet of mothers during gestation may impact offspring phenotype. This study evaluated the consequences of a maternal High-Protein (HP) diet during gestation on food preferences and phenotypic characteristics in adult rat offspring. Dams were fed a HP or a Normal-Protein (NP) isocaloric diet during gestation only. Weaned female pups were divided into 3 diet groups: NP control or one of two dietary self-selection (DSS) conditions. In DSS1, offspring had a free choice between proteins (100%) or a mix of carbohydrates (88%) and lipids (12%). In DSS2, the choice was between proteins (100%), carbohydrate (100%) or lipids (100%). DSS2 groups consumed more of their energy from protein and lipids, with a decreased carbohydrate intake (p < 0.0001) compared to NP groups, regardless of the maternal diet. Offspring from HP gestation dams fed the DSS2 diet (HPDSS2) had a 41.2% increase of total adiposity compared to NPDSS2 (p < 0.03). Liver Insulin receptor and Insulin substrate receptor 1 expression was decreased in offspring from HP compared to NP gestation dams. These results showed the specific effects of DSS and maternal diet and data suggested that adult, female offspring exposed to a maternal HP diet during foetal life were more prone to adiposity development, in response to postweaning food conditions.
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Peso Corporal , Dieta Rica em Proteínas , Preferências Alimentares/fisiologia , Insulina/metabolismo , Nutrientes/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Adiposidade/fisiologia , Animais , Composição Corporal , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Leptina/sangue , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Transdução de SinaisRESUMO
The aim of this systematic review was to assess the effect of fructo-oligosaccharide supplementation on glucose homeostasis. The search process was based on the selection of publications listed in the Pubmed-Medline database until April 2016 to identify studies evaluating the impact of short-chain fructo-oligosaccharides or oligofructose on glucose homeostasis. Twenty-nine trials were included in the systematic review and the meta-analysis was performed on twelve of these papers according to the inclusion criteria. Fasting blood concentrations of glucose and insulin were selected as pertinent criteria of glucose homeostasis for the meta-analysis. The consumption of fructo-oligosaccharides decreased fasting blood glycaemia levels, whatever the metabolic status (healthy, obese or diabetic) and diet (low-fat or high-fat) throughout the experiment. This reduction was linear with prebiotic dose (from 0 to 13% of the feed). Fasting insulinaemia also decreased linearly with fructo-oligosaccharide supplementation but the reduction was only significant in rodents fed a low-fat diet. Potential underlying mechanisms include gut bacterial fermentation of fructo-oligosaccharides to short-chain fatty acids (SCFA) and bacterial modulation of bile acids, both interacting with host metabolism. This systemic review, followed by the meta-analysis, provides evidence that fructo-oligosaccharide supplementation has a significant effect on glucose homeostasis whatever the health status and diet consumed by animals.
RESUMO
Clinical and animal studies have demonstrated beneficial effects of early consumption of dairy lipids and a probiotic, Lactobacillus fermentum (Lf), on infant gut physiology. The objective of this study was to investigate their long-term effects on gut microbiota and host entero-insular axis and metabolism. Piglets were suckled with a milk formula containing only plant lipids (PL), a half-half mixture of plant lipids and dairy lipids (DL), or this mixture supplemented with Lf (DL + Lf). They were weaned on a standard diet and challenged with a high-energy diet until postnatal day 140. DL and DL + Lf modulated gut microbiota composition and metabolism, increasing abundance of several Clostridia genera. Moreover, DL + Lf specifically decreased the faecal content of 2-oxoglutarate and lysine compared to PL and 5-aminovalerate compared to PL and DL. It also increased short-chain fatty acid concentrations like propionate compared to DL. Furthermore, DL + Lf had a beneficial effect on the endocrine function, enhancing caecal GLP-1 and GLP-1 meal-stimulated secretion. Correlations highlighted the consistent relationship between microbiota and gut physiology. Together, our results evidence a beneficial programming effect of DL + Lf in infant formula composition on faecal microbiota and entero-insular axis function.
Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Fórmulas Infantis/química , Lipídeos/administração & dosagem , Probióticos/administração & dosagem , Animais , Suplementos Nutricionais , Fezes/microbiologia , Humanos , Lactente , Limosilactobacillus fermentum/química , Lipídeos/química , Leite/química , Probióticos/química , Suínos , Porco MiniaturaRESUMO
Hyperglycemia markedly modifies gastro-duodenal motility. The question was raised whether hyperinsulinaemia, which is usually concomitant to hyperglycemia, could be the factor responsible for this effect through alteration of gastro-duodenal sensitivity. Indeed, vagal receptors are directly activated by insulin in lambs. However, insulin action significantly differs in ruminants and non-ruminants. The aim of our study was therefore to check (i) if insulin per se was able to modulate basal and distension induced discharges of duodenal vagal afferents in a monogatric animal model and (ii) if its action was direct or indirect through changes in gut compliance. Fourteen duodenal mechanoreceptors were studied in anaesthetized curarized pigs using the "single-fiber" method performed on the left cervical vagus. The characteristics of the vagal receptors were studied before (Control), and after (i) local insulin infusion in the gastroepiploic artery (IA), (ii) IV insulin perfusion inducing systemic hypoglycemia (IV), and (iii) during an euglycemic hyperinsulinemic clamp (EH). Basal recording, isobaric and isovolumetric distensions were performed in all experimental conditions. Basal discharge was significantly increased during IA (5.8+/-0.28 spikes/5 s), IV (6.6+/-0.30 spikes/5 s) and EH (5.7+/-0.25 spikes/5 s) compared to Control (4.4+/-0.27 spikes/5 s, p<0.05). Responses during isobaric and isovolumetric distensions were identical irrespective of the experimental condition. Gut compliance and intraluminal pressure during basal recording were not modified (p>0.05). In conclusion, insulin increased duodenal vagal mechanoreceptors basal activity but did not modulate the mechanosensitivity of the vagal units. Insulin-induced increase in basal discharge rate was due to hyperinsulinemia per se since it persisted during the euglycemic hyperinsulinemic clamp.