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Grases-Pintó B, Torres-Castro P, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation. J Nutr Biochem 2025; 135:109778. [PMID: 39374742 DOI: 10.1016/j.jnutbio.2024.109778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/04/2024] [Accepted: 10/01/2024] [Indexed: 10/09/2024]
Abstract
Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Paulina Torres-Castro
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Klinikum rechts der Isar, Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain
| | - María J Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain.
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
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Wang R, Patel D, Goruk S, Richard C, Field CJ. Feeding Docosahexaenoic Acid and Arachidonic Acid during Suckling and Weaning Contributes to Oral Tolerance Development by Beneficially Modulating the Intestinal Cytokine and Immunoglobulin Levels in an Allergy-Prone Brown Norway Rat Model. J Nutr 2024; 154:3790-3802. [PMID: 39401683 DOI: 10.1016/j.tjnut.2024.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 10/10/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Suckling and weaning arachidonic acid (ARA) + docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown. OBJECTIVE We aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development. METHODS Allergy-prone Brown Norway dams were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.45% ARA, 0.8% DHA) during suckling (0-3 wk). At weaning (3-8 wk), offspring were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.5% ARA, 0.5% DHA). At 3 wk, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for five consecutive days. At 7 wk, all offspring received an intraperitoneal OVA injection. At 8 wk, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related secretory immunoglobulin A (sIgA) and cytokines, ileum phospholipid and triglyceride fatty acid compositions, and fecal calprotectin. RESULTS Weaning ARA + DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P < 0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA + DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile [higher concentrations of mucosal IL-2 (P = 0.049) and sIgA (P = 0.033)]. OVA treatment resulted in a lower concentration of mucosal IL-6 (P = 0.026) regardless of dietary interventions. Offspring fed ARA + DHA during suckling and/or weaning had a higher concentration of mucosal transforming growth factor-beta (TGF-β) after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P = 0.04). CONCLUSIONS Early life dietary ARA + DHA supplementation to allergy-prone rats enhanced the DHA concentration in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2, and TGF-β levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.
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Affiliation(s)
- Ren Wang
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Dhruvesh Patel
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Caroline Richard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
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Alabiad MA, Elhasadi I, Alnasser SM, Alorini M, Alshaikh ABA, Jaber FA, Shalaby AM, Samy W, Heraiz AI, Mohammed Albakoush KM, Khairy DA. Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study. IRANIAN JOURNAL OF MEDICAL SCIENCES 2024; 49:46-56. [PMID: 38322160 PMCID: PMC10839141 DOI: 10.30476/ijms.2023.96905.2853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/23/2023] [Accepted: 03/04/2023] [Indexed: 02/08/2024]
Abstract
Background Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Results Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Conclusion Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.
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Affiliation(s)
- Mohamed Ali Alabiad
- Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ibtesam Elhasadi
- Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya
| | - Sulaiman Mohammed Alnasser
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim, University, Buraydah, Saudi Arabia
| | - Mohammed Alorini
- Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia
| | - Ahmed Baker A Alshaikh
- Department of Obstetrics and Gynecology, College of Medicine, Jouf University, Sakaka, Kingdom of Saudi Arabia
| | - Fatima A Jaber
- Department of Biology, College of Science, University of Jeddah, Jeddah, Kingdom of Saudi Arabia
| | - Amany Mohamed Shalaby
- Department of Histology and Cell Biology, School of Medicine, Tanta University, Tanta, Egypt
| | - Walaa Samy
- Department of Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed Ismail Heraiz
- Department of Gynecology and Obstetrics, School of Medicine, Zagazig University, Zagazig, Egypt
| | | | - Dina Ahmed Khairy
- Department of Pathology, School of Medicine, Beni-Suef University, Beni-Suef, Egypt
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Patel D, Munhoz J, Goruk S, Tsai S, Richard C, Field CJ. Maternal diet supplementation with high-docosahexaenoic-acid canola oil, along with arachidonic acid, promotes immune system development in allergy-prone BALB/c mouse offspring at 3 weeks of age. Eur J Nutr 2023; 62:2399-2413. [PMID: 37106253 DOI: 10.1007/s00394-023-03160-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 04/18/2023] [Indexed: 04/29/2023]
Abstract
PURPOSE To study the effects of feeding docosahexaenoic acid (DHA, derived from novel canola oil), with same amount of arachidonic acid (ARA), supplemented diet to lactating dams on the immune system development of suckled offspring using a T helper type-2 (Th2)-dominant BALB/c mouse. METHODS Dams received nutritionally complete control (no ARA or DHA) or DHA + ARA diet (1% DHA and 1% ARA of total fatty acids) from 5 days pre-parturition to the end of 3-week suckling period. After euthanization, relevant tissues were collected to study fatty acids, splenocyte phenotype and function (ex vivo cytokines with/without lipopolysaccharide (LPS, bacterial challenge) or phorbol myristate acetate + ionomycin (PMAi) stimulation). RESULTS Feeding dams a DHA diet significantly increased the mammary gland milk phospholipid concentration of DHA and ARA. This resulted in 60% higher DHA levels in splenocyte phospholipids of the pups although ARA levels showed no difference. In dams fed DHA diet, significantly higher proportion of CD27+ cytotoxic T cell (CTL) and CXCR3+ CCR6- Th (enriched in Th1) were observed than control, but there were no differences in the splenocyte function upon PMAi (non-specific lymphocyte stimulant) stimulation. Pups from DHA-fed dams showed significantly higher IL-1β, IFN-γ and TNF-α (inflammatory cytokines) by LPS-stimulated splenocytes. This may be due to higher proportion of CD86+ macrophages and B cells (all p's < 0.05) in these pups, which may influence T cell polarization. CONCLUSION Plant-based source of DHA in maternal diet resulted in higher ex vivo production of inflammatory cytokines by splenocytes due to change in their phenotype, and this can skew T cell towards Th1 response in a Th2-dominant BALB/c mouse.
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Affiliation(s)
- Dhruvesh Patel
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Jaqueline Munhoz
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Sue Tsai
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Caroline Richard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
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Galetaki DM, Cai CL, Bhatia KS, Chin V, Aranda JV, Beharry KD. Biomarkers of growth and carbohydrate metabolism in neonatal rats supplemented with fish oil and/or antioxidants during intermittent hypoxia. Growth Horm IGF Res 2023; 68:101513. [PMID: 36427361 DOI: 10.1016/j.ghir.2022.101513] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 10/14/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth requiring lipid supplementation. Lipids are targets of reactive oxygen species resulting in lipid peroxidation and cell death, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH. DESIGN Newborn rats (n = 18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2), or room air (RA), from birth (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At P21, plasma samples were assessed for glucose, insulin, glucokinase (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), corticosterone, and ghrelin. Liver was assessed for histopathology, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, GH binding protein (GHBP), and IGF binding protein (IGFBP)-3. RESULTS Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3. CONCLUSIONS Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.
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Affiliation(s)
- Despoina Myrsini Galetaki
- Department of Pediatrics, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
| | - Charles L Cai
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
| | - Kulsajan S Bhatia
- Department of Pediatrics, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
| | - Vivian Chin
- Department of Pediatrics, Division of Endocrinology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
| | - Jacob V Aranda
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA; Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; SUNY Eye Institute, Brooklyn, NY, USA
| | - Kay D Beharry
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA; Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; SUNY Eye Institute, Brooklyn, NY, USA.
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Rodent models of metabolic disorders: considerations for use in studies of neonatal programming. Br J Nutr 2022; 128:802-827. [PMID: 34551828 DOI: 10.1017/s0007114521003834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Epidemiologically, metabolic disorders have garnered much attention, perhaps due to the predominance of obesity. The early postnatal life represents a critical period for programming multifactorial metabolic disorders of adult life. Though altricial rodents are prime subjects for investigating neonatal programming, there is still no sufficiently generalised literature on their usage and methodology. This review focuses on establishing five approach-based models of neonatal rodents adopted for studying metabolic phenotypes. Here, some modelled interventions that currently exist to avoid or prevent metabolic disorders are also highlighted. We also bring forth recommendations, guidelines and considerations to aid research on neonatal programming. It is hoped that this provides a background to researchers focused on the aetiology, mechanisms, prevention and treatment of metabolic disorders.
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Morales-Ferré C, Franch À, Castell M, Olivares M, Rodríguez-Lagunas MJ, Pérez-Cano FJ. Staphylococcus epidermidis' Overload During Suckling Impacts the Immune Development in Rats. Front Nutr 2022; 9:916690. [PMID: 35859758 PMCID: PMC9289531 DOI: 10.3389/fnut.2022.916690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/13/2022] [Indexed: 11/20/2022] Open
Abstract
Mastitis is an inflammation of the mammary gland occurring in 3-33% of the breastfeeding mothers. The majority of mastitis cases have an infectious etiology. More than 75% of infectious mastitis are caused by Staphylococcus epidermidis and Staphylococcus aureus and involves breast milk microbiota alteration, which, may have an impact in lactating infant. The aim of this study was to analyze in rats during the suckling period and later in life the impact of a high and a low overload of Staphylococcus epidermidis, similarly as it occurs during the clinical and the subclinical mastitis, respectively. From days 2 to 21 of life, suckling rats were daily supplemented with low (Ls group) or high (Hs group) dose of S. epidermidis. Body weight and fecal humidity were periodically recorded. On days 21 and 42 of life, morphometry, hematological variables, intestinal gene expression, immunoglobulin (Ig) and cytokine profile and spleen cells' phenotype were measured. Although no differences were found in body weight, Ls and Hs groups showed higher body length and lower fecal humidity. Both doses induced small changes in lymphocytes subpopulations, reduced the plasma levels of Ig and delayed the Th1/Th2 balance causing a bias toward the Th2 response. No changes were found in cytokine concentration. The low dose affected the Tc cells intestinal homing pattern whereas the high dose had an impact on the hematological variables causing leukocytosis and lymphocytosis and also influenced the intestinal barrier maturation. In conclusion, both interventions with Staphylococcus epidermidis overload during suckling, affects the immune system development in short and long term.
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Affiliation(s)
- Carla Morales-Ferré
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain
| | | | - María J. Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain
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She Y, Mangat R, Tsai S, Proctor SD, Richard C. The Interplay of Obesity, Dyslipidemia and Immune Dysfunction: A Brief Overview on Pathophysiology, Animal Models, and Nutritional Modulation. Front Nutr 2022; 9:840209. [PMID: 35252310 PMCID: PMC8891442 DOI: 10.3389/fnut.2022.840209] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/20/2022] [Indexed: 12/14/2022] Open
Abstract
Obesity has emerged as a leading global health concern. It is characterized by chronic low-grade inflammation, which impairs insulin signaling, lipid metabolism and immune function. Recent findings from animal and clinical studies have begun to elucidate the underlying mechanisms of immune dysfunction seen in the context of obesity. Here, we provide a brief review on the current understanding of the interplay between obesity, dyslipidemia and immunity. We also emphasize the advantages and shortcomings of numerous applicable research models including rodents and large animal swine that aim at unraveling the molecular basis of disease and clinical manifestations. Although there is no perfect model to answer all questions at once, they are often used to complement each other. Finally, we highlight some emerging nutritional strategies to improve immune function in the context of obesity with a particular focus on choline and foods that contains high amounts of choline.
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Affiliation(s)
- Yongbo She
- Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- Metabolic and Cardiovascular Diseases Laboratory, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Rabban Mangat
- Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- Metabolic and Cardiovascular Diseases Laboratory, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Sue Tsai
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Spencer D. Proctor
- Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- Metabolic and Cardiovascular Diseases Laboratory, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Caroline Richard
- Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- Metabolic and Cardiovascular Diseases Laboratory, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
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Patel D, Newell M, Goruk S, Richard C, Field CJ. Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring. Front Nutr 2021; 8:769293. [PMID: 34790691 PMCID: PMC8592062 DOI: 10.3389/fnut.2021.769293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/28/2021] [Indexed: 01/02/2023] Open
Abstract
Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring. Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses. Results: ARA + DHA maternal diet resulted in higher (p < 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls. Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.
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Affiliation(s)
- Dhruvesh Patel
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Marnie Newell
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Caroline Richard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
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10
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McMillen S, Lönnerdal B. Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism, Growth, and Central Nervous System Development in Sprague Dawley Rat Pups. Nutrients 2021; 13:1406. [PMID: 33921980 PMCID: PMC8143548 DOI: 10.3390/nu13051406] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 02/05/2023] Open
Abstract
Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.
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Affiliation(s)
| | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, CA 95616, USA;
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11
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Grases-Pintó B, Abril-Gil M, Torres-Castro P, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. Rat Milk and Plasma Immunological Profile throughout Lactation. Nutrients 2021; 13:nu13041257. [PMID: 33920419 PMCID: PMC8070501 DOI: 10.3390/nu13041257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/26/2021] [Accepted: 04/07/2021] [Indexed: 01/02/2023] Open
Abstract
The composition of bioactive factors with immune activity in human breast milk is widely studied. However, the knowledge on rat milk immune factors during the whole lactation period is still scarce. This study aimed to analyze rat breast milk’s immunoglobulin (Ig) content and some critical adipokines and growth factors throughout the lactation period, and to assess relationships with corresponding plasma levels. During lactation, milk concentration of the transforming growth factor (TGF)-β2 and -β3 showed a punctual increase in the first week, whereas adiponectin and leptin remained stable. In the second period of lactation (d14–21), despite the increase in the milk epidermal growth factor (EGF), a decrease in fibroblast growth factor 21 (FGF21) was detected at day 21. Milk IgA concentration had a progressive increase during lactation, while no significant changes were found in IgM and IgG. Regarding plasma levels, a decrease in all studied adipokines was observed in the second period of lactation, with the exception of IgA and TGF-β1, which reached their highest values at the end of the study. A positive correlation in IgM, IgG, and adipokine concentration was detected between milk and plasma compartments. In summary, the changes in the pattern of these bioactive compounds in rat milk and plasma and their relationships during lactation are established.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Paulina Torres-Castro
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - María J. Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
- Correspondence: ; Tel.: +34-934-024-505
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (B.G.-P.); (M.A.-G.); (P.T.-C.); (M.C.); (M.J.R.-L.); (À.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
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12
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Ramos L, Lunney JK, Gonzalez-Juarrero M. Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models. Dis Model Mech 2020; 13:dmm045740. [PMID: 32988990 PMCID: PMC7520460 DOI: 10.1242/dmm.045740] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette-Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.
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Affiliation(s)
- Laylaa Ramos
- Mycobacteria Research Laboratories, Microbiology Immunology and Pathology Department, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, USA
| | - Joan K Lunney
- Animal Parasitic Diseases Laboratory, BARC, NEA, ARS, USDA Building 1040, Room 103, Beltsville, MD 20705, USA
| | - Mercedes Gonzalez-Juarrero
- Mycobacteria Research Laboratories, Microbiology Immunology and Pathology Department, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, USA
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Torres-Castro P, Grases-Pintó B, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. Modulation of the Systemic Immune Response in Suckling Rats by Breast Milk TGF-β2, EGF and FGF21 Supplementation. Nutrients 2020; 12:nu12061888. [PMID: 32599899 PMCID: PMC7353385 DOI: 10.3390/nu12061888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/17/2020] [Accepted: 06/21/2020] [Indexed: 12/17/2022] Open
Abstract
Breast milk is a rich fluid containing bioactive compounds such as specific growth factors (GF) that contribute to maturation of the immune system in early life. The aim of this study was to determine whether transforming growth factor-β2 (TGF-β2), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), compounds present in breast milk, could promote systemic immune maturation. For this purpose, newborn Wistar rats were daily supplemented with these GF by oral gavage during the suckling period (21 days of life). At day 14 and 21 of life, plasma for immunoglobulin (Ig) quantification was obtained and spleen lymphocytes were isolated, immunophenotyped and cultured to evaluate their ability to proliferate and release cytokines. The main result was obtained at day 14, when supplementation with EGF increased B cell proportion to reach levels observed at day 21. At the end of the suckling period, all GF increased the plasma levels of IgG1 and IgG2a isotypes, FGF21 balanced the Th1/Th2 cytokine response and both EGF and FGF21 modified splenic lymphocyte composition. These results suggested that the studied milk bioactive factors, mainly EGF and FGF21, may have modulatory roles in the systemic immune responses in early life, although their physiological roles remain to be established.
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Affiliation(s)
- Paulina Torres-Castro
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Blanca Grases-Pintó
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - María J. Rodríguez-Lagunas
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
- Correspondence: ; Tel.: +34-93-402-45-05
| | - Àngels Franch
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
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14
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Weström B, Arévalo Sureda E, Pierzynowska K, Pierzynowski SG, Pérez-Cano FJ. The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals. Front Immunol 2020; 11:1153. [PMID: 32582216 PMCID: PMC7296122 DOI: 10.3389/fimmu.2020.01153] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 05/11/2020] [Indexed: 12/16/2022] Open
Abstract
The gut is an efficient barrier which protects against the passage of pathogenic microorganisms and potential harmful macromolecules into the body, in addition to its primary function of nutrient digestion and absorption. Contrary to the restricted macromolecular passage in adulthood, enhanced transfer takes place across the intestines during early life, due to the high endocytic capacity of the immature intestinal epithelial cells during the fetal and/or neonatal periods. The timing and extent of this enhanced endocytic capacity is dependent on animal species, with a prominent non-selective intestinal macromolecular transfer in newborn ungulates, e.g., pigs, during the first few days of life, and a selective transfer of mainly immunoglobulin G (IgG), mediated by the FcRn receptor, in suckling rodents, e.g., rats and mice. In primates, maternal IgG is transferred during fetal life via the placenta, and intestinal macromolecular transfer is largely restricted in human neonates. The period of intestinal macromolecular transmission provides passive immune protection through the transfer of IgG antibodies from an immune competent mother; and may even have extra-immune beneficial effects on organ maturation in the offspring. Moreover, intestinal transfer during the fetal/neonatal periods results in increased exposure to microbial and food antigens which are then presented to the underlying immune system, which is both naïve and immature. This likely stimulates the maturation of the immune system and shifts the response toward tolerance induction instead of activation or inflammation, as usually seen in adulthood. Ingestion of mother's milk and the dietary transition to complex food at weaning, as well as the transient changes in the gut microbiota during the neonatal period, are also involved in the resulting immune response. Any disturbances in timing and/or balance of these parallel processes, i.e., intestinal epithelial maturation, luminal microbial colonization and mucosal immune maturation due to, e.g., preterm birth, infection, antibiotic use or nutrient changes during the neonatal period, might affect the establishment of the immune system in the infant. This review will focus on how differing developmental processes in the intestinal epithelium affect the macromolecular passage in different species and the possible impact of such passage on the establishment of immunity during the critical perinatal period in young mammals.
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Affiliation(s)
- Björn Weström
- Department of Biology, Lund University, Lund, Sweden
| | - Ester Arévalo Sureda
- Precision Livestock and Nutrition Unit, TERRA Teaching and Research Centre, Gembloux Agro-Biotech, University of Liège, Gembloux, Belgium
| | - Kateryna Pierzynowska
- Department of Biology, Lund University, Lund, Sweden
- Department of Animal Physiology, Kielanowski Institute of Animal Physiology and Nutrition, Jablonna, Poland
| | - Stefan G. Pierzynowski
- Department of Biology, Lund University, Lund, Sweden
- Department of Medical Biology, Institute of Rural Health, Lublin, Poland
| | - Francisco-José Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
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15
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Azagra-Boronat I, Tres A, Massot-Cladera M, Franch À, Castell M, Guardiola F, Pérez-Cano FJ, Rodríguez-Lagunas MJ. Lactobacillus fermentum CECT5716 supplementation in rats during pregnancy and lactation affects mammary milk composition. J Dairy Sci 2020; 103:2982-2992. [PMID: 32008776 DOI: 10.3168/jds.2019-17384] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 12/02/2019] [Indexed: 12/11/2022]
Abstract
Lactobacillus fermentum CECT5716 has shown immunomodulatory action and reduction of infections; therefore, it is suggested to be appropriate for use in early life. The present study aimed to assess the effects of the supplementation of L. fermentum CECT5716 in rats during gestation and lactation periods on the composition of some mammary milk components such as microbiota, fatty acid (FA) profile, and immunoglobulins. Wistar rats were supplemented by oral gavage with 1010 cfu/d of Lactobacillus fermentum CECT5716 (n = 6) or vehicle (n = 6) for 5 wk, comprising the 3 wk of gestation and the first 2 wk of lactation. At the end of the intervention, milk, mammary glands, and cecal contents were obtained for the tracking of the probiotic strain by nested PCR-quantitative PCR. Additionally, milk samples were used for the analysis of microbiota by 16S rRNA sequencing, FA by gas chromatography-flame ionization detector, and immunoglobulin by Luminex (Luminex Corporation, Austin, TX). Although L. fermentum CECT5716 administration did not modify the overall composition of milk microbiota, the strain was detected in 50% of the milk samples of rats supplemented with the probiotic. Moreover, probiotic administration induced beneficial changes in the FA composition of milk by increasing total PUFA, including linoleic and α-linolenic acids, and decreasing the proportion of palmitic acid. Finally, the milk of the rats treated with the probiotic showed a 2-fold increase of IgA levels. The supplementation with L. fermentum CECT5716 during pregnancy and lactation periods improved the milk composition of FA and immunoglobulins. These effects were not linked to the presence of the strain in milk, thus suggesting that the mechanism is connected to intestinal compartment. These findings provide novel insight into a potential new approach for infants to benefit from better nutrition, development of a healthy immune system and microbiota, and protection from gastrointestinal infections.
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Affiliation(s)
- Ignasi Azagra-Boronat
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain
| | - Alba Tres
- Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain; Department of Nutrition, Food Science and Gastronomy, Torribera Food Science Campus, Faculty of Pharmacy and Food Science, University of Barcelona, Santa Coloma de Gramenet 08921, Spain
| | - Malén Massot-Cladera
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain
| | - Francesc Guardiola
- Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain; Department of Nutrition, Food Science and Gastronomy, Torribera Food Science Campus, Faculty of Pharmacy and Food Science, University of Barcelona, Santa Coloma de Gramenet 08921, Spain
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain.
| | - M José Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona 08028, Spain; Nutrition and Food Safety Research Institute, Santa Coloma de Gramenet 08921, Spain
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Associations of Breast Milk Microbiota, Immune Factors, and Fatty Acids in the Rat Mother-Offspring Pair. Nutrients 2020; 12:nu12020319. [PMID: 31991792 PMCID: PMC7071194 DOI: 10.3390/nu12020319] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 01/17/2020] [Accepted: 01/21/2020] [Indexed: 12/21/2022] Open
Abstract
The present study aimed to analyze the rat breast milk profile of fatty acids (FA), immunoglobulins (Ig), microbiota, and their relationship, and to further assess their associations in the mother–offspring pair. Dams were monitored during the three weeks of gestation, allowed to deliver at term, and followed during two weeks of lactation. At the end of the study, milk was obtained from the dams for the analysis of fatty acids, microbiota composition, immunoglobulins, and cytokines. Moreover, the cecal content and plasma were obtained from both the dams and pups to study the cecal microbiota composition and the plasmatic levels of fatty acids, immunoglobulins, and cytokines. Rat breast milk lipid composition was ~65% saturated FA, ~15% monounsaturated FA, and ~20% polyunsaturated FA. Moreover, the proportions of IgM, IgG, and IgA were ~2%, ~88%, and ~10%, respectively. Breast milk was dominated by members of Proteobacteria, Firmicutes, and Bacteroidetes phyla. In addition, forty genera were shared between the milk and cecal content of dams and pups. The correlations performed between variables showed, for example, that all IgGs subtypes correlated between the three compartments, evidencing their association in the mother-milk-pup line. We established the profile of FA, Ig, and the microbiota composition of rat breast milk. Several correlations in these variables evidenced their association through the mother-milk-pup line. Therefore, it would be interesting to perform dietary interventions during pregnancy and/or lactation that influence the quality of breast milk and have an impact on the offspring.
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Bruce M, Streifel KM, Boosalis CA, Heuer L, González EA, Li S, Harvey DJ, Lein PJ, Van de Water J. Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain. J Neuroinflammation 2019; 16:200. [PMID: 31672161 PMCID: PMC6822372 DOI: 10.1186/s12974-019-1569-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 08/29/2019] [Indexed: 12/17/2022] Open
Abstract
Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells. Electronic supplementary material The online version of this article (10.1186/s12974-019-1569-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Matthew Bruce
- MIND Institute, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA.,Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, UC Davis School of Medicine, UC Davis MIND Institute, 6512 Genome and Biomedical Sciences Facility 451 Health Sciences Drive, Davis, CA, 95616-5270, USA
| | - Karin M Streifel
- MIND Institute, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA.,Department of Molecular Bioscience, University of California, Davis School of Veterinary Medicine, Davis, CA, 95616, USA.,Department of Biology, Regis University, Denver, CO, 80221, USA
| | - Casey A Boosalis
- Department of Molecular Bioscience, University of California, Davis School of Veterinary Medicine, Davis, CA, 95616, USA
| | - Luke Heuer
- MIND Institute, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA.,Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, UC Davis School of Medicine, UC Davis MIND Institute, 6512 Genome and Biomedical Sciences Facility 451 Health Sciences Drive, Davis, CA, 95616-5270, USA
| | - Eduardo A González
- Department of Molecular Bioscience, University of California, Davis School of Veterinary Medicine, Davis, CA, 95616, USA
| | - Shuyang Li
- Department of Public Health Sciences, University of California, Davis School of Medicine, Davis, CA, 95616, USA
| | - Danielle J Harvey
- Department of Public Health Sciences, University of California, Davis School of Medicine, Davis, CA, 95616, USA
| | - Pamela J Lein
- MIND Institute, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA.,Department of Molecular Bioscience, University of California, Davis School of Veterinary Medicine, Davis, CA, 95616, USA
| | - Judy Van de Water
- MIND Institute, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA. .,Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, UC Davis School of Medicine, UC Davis MIND Institute, 6512 Genome and Biomedical Sciences Facility 451 Health Sciences Drive, Davis, CA, 95616-5270, USA.
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18
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Grases-Pintó B, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Burleigh S, Fåk Hållenius F, Prykhodko O, Pérez-Cano FJ, Franch À. Influence of Leptin and Adiponectin Supplementation on Intraepithelial Lymphocyte and Microbiota Composition in Suckling Rats. Front Immunol 2019; 10:2369. [PMID: 31708912 PMCID: PMC6795087 DOI: 10.3389/fimmu.2019.02369] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 09/20/2019] [Indexed: 12/19/2022] Open
Abstract
Dietary components in early life play a role in both microbiota and intestinal immune system maturation in mammalian species. Adipokines, as endogenously produced hormones from breast milk, may have an impact on this process. The aim of the present study was to establish the influence of leptin and adiponectin supplementation during suckling on the intraepithelial lymphocyte composition, intestinal barrier function, intestinal gene expression, and gut microbiota in rat. For this purpose, newborn Wistar rats were supplemented daily with leptin, adiponectin, or whey protein concentrate during the first 21 days of life. Lymphocyte composition was established by immunofluorescence staining and flow cytometry analysis; intestinal gene expression by real-time PCR and cecal microbiota were analyzed through 16S rRNA gene sequencing. Although leptin and adiponectin were able to increase the Tc TCRαβ+ and NKT cell proportion, they decreased the NK cell percentage in IEL. Moreover, adipokine supplementation differentially modified CD8+ IEL. While the supplementation of leptin increased the proportion of CD8αα+ IEL (associated to a more intestinal phenotype), adiponectin enhanced that of CD8αβ+ (related to a peripheral phenotype). Furthermore, both adipokines enhanced the gene expression of TNF-α, MUC-2, and MUC-3, and decreased that of FcRn. In addition, the adipokine supplementations decreased the abundance of the Proteobacteria phylum and the presence of Blautia. Moreover, leptin-supplemented animals had lower relative abundance of Sutterella and a higher proportion of Clostridium genus, among others. However, supplementation with adiponectin resulted in lower abundance of the Roseburia genus and a higher proportion of the Enterococcus genus. In conclusion, the supplementation with leptin and adiponectin throughout the suckling period had an impact on both the IEL composition and the gut microbiota pattern, suggesting a modulatory role of these adipokines on the development of intestinal functionality.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Maria J Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Stephen Burleigh
- Food for Health Science Centre, Lund University, Lund, Sweden.,Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Frida Fåk Hållenius
- Food for Health Science Centre, Lund University, Lund, Sweden.,Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Olena Prykhodko
- Food for Health Science Centre, Lund University, Lund, Sweden.,Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.,Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
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Grases-Pintó B, Torres-Castro P, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. A Preterm Rat Model for Immunonutritional Studies. Nutrients 2019; 11:nu11050999. [PMID: 31052461 PMCID: PMC6566403 DOI: 10.3390/nu11050999] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 04/26/2019] [Accepted: 04/29/2019] [Indexed: 12/14/2022] Open
Abstract
Neonates are born with an immature immune system, which develops during the first stages of life. This early immaturity is more acute in preterm newborns. The aim of the present study was to set up a preterm rat model, in which representative biomarkers of innate and adaptive immunity maturation that could be promoted by certain dietary interventions are established. Throughout the study, the body weight was registered. To evaluate the functionality of the intestinal epithelial barrier, in vivo permeability to dextrans was measured and a histomorphometric study was performed. Furthermore, the blood cell count, phagocytic activity of blood leukocytes and plasmatic immunoglobulins (Ig) were determined. Preterm rats showed lower erythrocyte and platelet concentration but a higher count of leukocytes than the term rats. Although there were no changes in the granulocytes’ ability to phagocytize, preterm monocytes had lower phagocytic activity. Moreover, lower plasma IgG and IgM concentrations were detected in preterm rats compared to full-term rats, without affecting IgA. Finally, the intestinal study revealed lower permeability in preterm rats and reduced goblet cell size. Here, we characterized a premature rat model, with differential immune system biomarkers, as a useful tool for immunonutritional studies aimed at boosting the development of the immune system.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Paulina Torres-Castro
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Mar Abril-Gil
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - María J Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
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Rucker RB, Watkins BA. Inadequate diet descriptions: a conundrum for animal model research. Nutr Res 2019; 65:1-3. [DOI: 10.1016/j.nutres.2019.03.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 03/14/2019] [Accepted: 03/15/2019] [Indexed: 10/27/2022]
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Leptin and adiponectin supplementation modifies mesenteric lymph node lymphocyte composition and functionality in suckling rats. Br J Nutr 2019; 119:486-495. [PMID: 29508690 DOI: 10.1017/s0007114517003786] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
At birth, when immune responses are insufficient, there begins the development of the defence capability against pathogens. Leptin and adiponectin, adipokines that are present in breast milk, have been shown to play a role in the regulation of immune responses. We report here, for the first time, the influence of in vivo adipokine supplementation on the intestinal immune system in early life. Suckling Wistar rats were daily supplemented with leptin (0·7 μg/kg per d, n 36) or adiponectin (35 μg/kg per d, n 36) during the suckling period. The lymphocyte composition, proliferation and cytokine secretion from mesenteric lymph node lymphocytes (on days 14 and 21), as well as intestinal IgA and IgM concentration (day 21), were evaluated. At day 14, leptin supplementation significantly increased the TCRαβ + cell proportion in mesenteric lymph nodes, in particular owing to an increase in the TCRαβ + CD8+ cell population. Moreover, the leptin or adiponectin supplementation promoted the early development CD8+ cells, with adiponectin being the only adipokine capable of enhancing the lymphoproliferative ability at the end of the suckling period. Although leptin decreased intestinal IgA concentration, it had a trophic effect on the intestine in early life. Supplementation of both adipokines modulated the cytokine profile during (day 14) and at the end (day 21) of the suckling period. These results suggest that leptin and adiponectin during suckling play a role in the development of mucosal immunity in early life.
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Rotavirus Double Infection Model to Study Preventive Dietary Interventions. Nutrients 2019; 11:nu11010131. [PMID: 30634561 PMCID: PMC6357201 DOI: 10.3390/nu11010131] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 12/27/2018] [Accepted: 01/07/2019] [Indexed: 12/22/2022] Open
Abstract
Rotaviruses are the main cause of acute diarrhea among young children worldwide with an increased frequency of reinfection. Several life style factors, such as dietary components, may influence such processes by affecting the outcome of the first rotavirus infection and therefore having a beneficial impact on the anti-rotavirus immune responses during any subsequent reinfections. The aim of this research was to develop a double-infection model in rat that mimics real-life clinical scenarios and would be useful in testing whether nutritional compounds can modulate the rotavirus-associated disease and immune response. Three experimental designs and a preventive dietary-like intervention were conducted in order to achieve a differential response in the double-infected animals compared to the single-infected ones and to study the potential action of a modulatory agent in early life. Diarrhea was only observed after the first infection, with a reduction of fecal pH and fever. After the second infection an increase in body temperature was also found. The immune response against the second infection was regulated by the preventive effect of the dietary-like intervention during the first infection in terms of specific antibodies and DTH. A rotavirus-double-infection rat model has been developed and is suitable for use in future preventive dietary intervention studies.
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TGF-β2, EGF, and FGF21 Growth Factors Present in Breast Milk Promote Mesenteric Lymph Node Lymphocytes Maturation in Suckling Rats. Nutrients 2018; 10:nu10091171. [PMID: 30150532 PMCID: PMC6163676 DOI: 10.3390/nu10091171] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 08/22/2018] [Accepted: 08/24/2018] [Indexed: 01/12/2023] Open
Abstract
Breast milk, due to its large number of nutrients and bioactive factors, contributes to optimal development and immune maturation in early life. In this study, we aimed to assess the influence of some growth factors present in breast milk, such as transforming growth factor-β2 (TGF-β2), epidermal growth factor (EGF), and fibroblast growth factor 21 (FGF21), on the immune response development. Newborn Wistar rats were supplemented daily with TGF-β2, EGF, or FGF21, throughout the suckling period. At day 14 and 21 of life, lymphocytes from mesenteric lymph nodes (MLNs) were isolated, immunophenotyped, and cultured to evaluate their ability to proliferate and release cytokines. The main results demonstrated that supplementation with TGF-β2, EGF, or FGF21 modified the lymphocyte composition in MLNs. At day 14, all supplementations were able to induce a lower percentage of natural killer (NK) cells with the immature phenotype (CD8+), and they reduced the CD8αα/CD8αβ ratio at day 21. Moreover, the cytokine pattern was modified by the three treatments, with a down regulation of interleukin (IL)-13 secretion. These results showed the contribution of these growth factors in the lymphocytes MLNs immune maturation during the neonatal period.
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Camps-Bossacoma M, Pérez-Cano FJ, Franch À, Castell M. Theobromine Is Responsible for the Effects of Cocoa on the Antibody Immune Status of Rats. J Nutr 2018; 148:464-471. [PMID: 29546302 DOI: 10.1093/jn/nxx056] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 11/28/2017] [Indexed: 12/27/2022] Open
Abstract
Background A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties. Objectives This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition. Methods Three-week-old female Lewis rats were fed either a standard diet (AIN-93M; RF group), a 10% cocoa diet (CC group), or a 0.25% theobromine diet (the same amount provided by the cocoa diet; TB group) in 2 separate experiments that lasted 19 (experiment 1) or 8 (experiment 2) d. Serum IgG, IgM, IgA, and intestinal secretory IgA (sIgA) concentrations were determined. In addition, at the end of experiment 2, thymus, mesenteric lymph node (MLN), and spleen lymphocyte populations were analyzed. Results Both CC and TB groups in experiments 1 and 2 showed similar serum IgG, IgM, and IgA and intestinal sIgA concentrations, which were lower than those in the RF group (46-98% lower in experiment 1 and 23-91% lower in experiment 2; P < 0.05). In addition, in experiment 2, the cocoa and theobromine diets similarly changed the thymocyte composition by increasing CD4-CD8- (+133%) and CD4+CD8- (+53%) proportions (P < 0.01), changed the MLN composition by decreasing the percentage of T-helper (Th) lymphocytes (-3%) (P = 0.015), and changed the spleen composition by increasing the proportion of Th lymphocytes (+9%) (P < 0.001) after 1 wk of diet treatment. Conclusions The theobromine in cocoa plays an immunoregulatory role that is responsible for cocoa's influence on both systemic and intestinal antibody concentrations and also for modifying lymphoid tissue lymphocyte composition in young healthy Lewis rats. The majority of these changes are observed after a single week of being fed a diet containing 0.25% theobromine.
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Affiliation(s)
- Mariona Camps-Bossacoma
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Nutrition and Food Safety Research Institute, University of Barcelona, Barcelona, Spain
| | - Francisco J Pérez-Cano
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Nutrition and Food Safety Research Institute, University of Barcelona, Barcelona, Spain
| | - Àngels Franch
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Nutrition and Food Safety Research Institute, University of Barcelona, Barcelona, Spain
| | - Margarida Castell
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Nutrition and Food Safety Research Institute, University of Barcelona, Barcelona, Spain
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25
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Sureda EA, Gidlund C, Weström B, Prykhodko O. Induction of precocious intestinal maturation in T-cell deficient athymic neonatal rats. World J Gastroenterol 2017; 23:7531-7540. [PMID: 29204053 PMCID: PMC5698246 DOI: 10.3748/wjg.v23.i42.7531] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 07/31/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether gut maturation could be induced precociously in an athymic T-cell deficient neonatal rat model.
METHODS Fourteen day-old athymic (nude) rats (NIH-Foxn1rnu) were gavaged with either phytohaemagglutinin - a lectin from red kidney beans (PHA); trypsin - a protease (Prot); or water - vehicle (control) as a single dose on one day or once a day for 3-day. The nude rats were either nurtured by their mothers or cross-fostered by conventional foster dams of the Sprague-Dawley strain from days 3-5 after birth. At 17 d of age, 72 h after administration of the first treatment, intestinal macromolecular permeability was tested in vivo, prior to euthanasia, after which blood and gut organs were sampled.
RESULTS Provocation with both, PHA and protease, resulted in increased gut growth and maturation in nude rat pups independent of nursing. Foetal-type enterocytes were replaced by non-vacuolated adult-type enterocytes in the distal small intestine epithelium. Decreased intestinal macromolecular permeability (gut closure) was observed, with reduced permeability markers (BIgG and BSA, P < 0.001) in circulation. Increased pancreatic function, with an increased trypsin to protein ratio in pancreas homogenates, was observed independent of nursing in the nude pups. Immunostaining showed the presence of a few CD3+-cells in the intestinal mucosa of the nude pups. The number of CD3+-cells remained unaltered by provocation and no differences were observed between the nursing sets. Growth and vitality of the nude pups were dependent on nurturing, since cross-fostering by conventional dams increased their macromolecular absorptive capacity (BSA, P < 0.05), as well as their passive immunity (RIgG, P < 0.05).
CONCLUSION Precocious gut maturation can be induced by enteral provocation in athymic rat pups, similarly to in euthymic pups, thus showing an independence from thymus-derived T-cells.
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Affiliation(s)
| | - Catherine Gidlund
- Department of Biology, Faculty of Science, Lund University, Lund 22362, Sweden
| | - Björn Weström
- Department of Biology, Faculty of Science, Lund University, Lund 22362, Sweden
| | - Olena Prykhodko
- Department of Biology, Faculty of Science, Lund University, Lund 22362, Sweden
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26
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Hadley KB, Guimont-Desrochers F, Bailey-Hall E, Salem N, Yurko-Mauro K, Field CJ. Supplementing dams with both arachidonic and docosahexaenoic acid has beneficial effects on growth and immune development. Prostaglandins Leukot Essent Fatty Acids 2017; 126:55-63. [PMID: 29031396 DOI: 10.1016/j.plefa.2017.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 09/02/2017] [Accepted: 09/05/2017] [Indexed: 12/15/2022]
Abstract
Omega-3 long-chain polyunsaturated fatty acids (LCPUFAS) modulate immune cells in vitro and in vivo. This study investigated the effects of enriching the maternal diet with the n-6 and n-3 LCPUFAs, arachidonic (20:4n-6, 0.6%wt ARA) and docosahexaenoic acid (22:6n-3, 0.32%wt DHA), or 1:1 and 2:1 ratios (ARA: DHA) on total lipids in milk, total lipids, and immunophenotypes in plasma, lymph nodes, and spleen from isolated immune cells from 28d old pups. From day 15 of gestation to day 3 pp, Sprague-Dawley dams were fed a commercial chow. On day 3 pp litters were culled and pups (4 males and 2 females) randomly cross-fostered to dams who were randomized to one of the 5 experimental diets resulting in 20 male and 10 female pups/diet group. Dams fed ARA or ARA: DHA had 28-36% more 20:4n-6 in milk and feeding DHA or ARA: DHA doubled 22:6n-3 in milk lipids (P<0.05). Feeding 1:1 or 2:1 ARA: DHA resulted in greater pup weight at weaning (P<0.05). Compared to the control pups, ARA + DHA fed pups had a lower proportion of splenic CD45RA+ lymphocytes. In summary, postpartum supplementation with a combination of ARA + DHA, compared to ARA or DHA alone, resulted in a higher content of ARA and DHA in dam's milk and tissues and had positive effects on growth, accompanied by evidence of progression toward a mature immune phenotype, and suggests a need for ARA when DHA is supplemented in the early diet. Additional investigations are needed of ARA immunomodulation to better understand and estimate nutritional requirements for LCPUFAs during early development.
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Affiliation(s)
- K B Hadley
- Clinical Research Department, DSM Nutritional Products, Columbia, MD 21045, USA.
| | | | - E Bailey-Hall
- Clinical Research Department, DSM Nutritional Products, Columbia, MD 21045, USA
| | - N Salem
- Clinical Research Department, DSM Nutritional Products, Columbia, MD 21045, USA
| | - K Yurko-Mauro
- Clinical Research Department, DSM Nutritional Products, Columbia, MD 21045, USA
| | - C J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada, T6G 2E1
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Richard C, Lewis ED, Goruk S, Wadge E, Curtis JM, Jacobs RL, Field CJ. Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring. Nutrients 2017; 9:E567. [PMID: 28574475 PMCID: PMC5490546 DOI: 10.3390/nu9060567] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 05/18/2017] [Accepted: 05/31/2017] [Indexed: 12/23/2022] Open
Abstract
Dietary choline is essential during lactation, but few studies have examined the implications of feeding a mixture of choline forms on immune function. This study investigates the impact of feeding lactating dams different mixtures of choline forms, similar to those in human diets, on the development and later immune function of suckled offspring. Sprague-Dawley lactating dams (n = 6/diet) were randomized to consume one of three diets, containing 1 g/kg choline: Control (100% free choline (FC)), Mixed Choline (MC: 50% phosphatidylcholine (PC), 25% FC, 25% glycerophosphocholine (GPC)), or High GPC (HGPC: 75% GPC, 12.5% PC, 12.5% FC). At weaning, female pups (n = 2/dam) were fed the Control diet until 10 weeks. At 3 weeks, MC and HGPC pups were heavier and their splenocytes had a higher proportion of helper T cells expressing CD25 and CD28 and produced less interferon gamma (IFN-γ) and tumor-necrosis factor-α (TNF-α) after Concanavalin A stimulation vs. Control pups (p < 0.05). At 10 weeks, MC and HGPC offspring had a lower proportion of macrophages and dendritic cells and produced less interleukin (IL)-1β but more IL-10 after lipopolysaccharide stimulation vs. Control pups (p < 0.05). In summary, feeding mixed choline diets during lactation improved T cell phenotype/function at the end of suckling and programmed a less inflammatory response later in life.
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Affiliation(s)
- Caroline Richard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - Erin D Lewis
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
- Jean Mayer United States Department of Agriculture, Human Nutrition Center on Aging, Tufts University, Boston, MA 02111, USA.
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - Emily Wadge
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - Jonathan M Curtis
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - René L Jacobs
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
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Abstract
The immune system of preterm infants is immature, placing them at increased risk for serious immune-related complications. Human milk provides a variety of immune protective and immune maturation factors that are beneficial to the preterm infant's poorly developed immune system. The most studied immune components in human milk include antimicrobial proteins, maternal leukocytes, immunoglobulins, cytokines and chemokines, oligosaccharides, gangliosides, nucleotides, and long-chain polyunsaturated fatty acids. There is growing evidence that these components contribute to the lower incidence of immune-related conditions in the preterm infant. Therefore, provision of these components in human milk, donor milk, or formula may provide immunologic benefits.
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A fermented milk concentrate and a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides protect suckling rats from rotavirus gastroenteritis. Br J Nutr 2017; 117:209-217. [PMID: 28166850 DOI: 10.1017/s0007114516004566] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Human milk contains bioactive compounds that confer a protective role against gastrointestinal infections. In order to find supplements for an infant formula able to mimic these benefits of breast-feeding, two different concepts were tested. The products consisted of the following: (1) a Bifidobacterium breve- and Streptococcus thermophilus-fermented formula and (2) a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides with pectin-derived acidic oligosaccharides. A rotavirus infection suckling rat model was used to evaluate improvements in the infectious process and in the immune response of supplemented animals. Both nutritional concepts caused amelioration of the clinical symptoms, even though this was sometimes hidden by softer stool consistency in the supplemented groups. Both products also showed certain modulation of immune response, which seemed to be enhanced earlier and was accompanied by a faster resolution of the process. The viral shedding and the in vitro blocking assay suggest that these products are able to bind the viral particles, which can result in a milder infection. In conclusion, both concepts evaluated in this study showed interesting protective properties against rotavirus infection, which deserve to be investigated further.
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Rigo-Adrover MDM, Franch À, Castell M, Pérez-Cano FJ. Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life. PLoS One 2016; 11:e0166082. [PMID: 27820846 PMCID: PMC5098803 DOI: 10.1371/journal.pone.0166082] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 10/21/2016] [Indexed: 01/16/2023] Open
Abstract
This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEβ7+ and CD62L+ cells in the MLN and that of the integrin αEβ7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life.
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Affiliation(s)
- Maria del Mar Rigo-Adrover
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, University of Barcelona (UB), Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Santa Coloma de Gramenet, Barcelona, Spain
| | - Àngels Franch
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, University of Barcelona (UB), Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Santa Coloma de Gramenet, Barcelona, Spain
| | - Margarida Castell
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, University of Barcelona (UB), Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Santa Coloma de Gramenet, Barcelona, Spain
| | - Francisco José Pérez-Cano
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, University of Barcelona (UB), Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Santa Coloma de Gramenet, Barcelona, Spain
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Richard C, Lewis ED, Goruk S, Field CJ. A Dietary Supply of Docosahexaenoic Acid Early in Life Is Essential for Immune Development and the Establishment of Oral Tolerance in Female Rat Offspring. J Nutr 2016; 146:2398-2406. [PMID: 27683871 DOI: 10.3945/jn.116.237149] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 09/02/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The early postnatal period is critical for immunity, and feeding docosahexaenoic acid (DHA) has been demonstrated to affect immune development. OBJECTIVE The objective of this study was to determine the importance of feeding DHA during suckling and/or weaning on immune function and oral tolerance (OT). METHODS Sprague-Dawley rats were randomly assigned to 1 of 2 nutritionally adequate diets throughout lactation (21 d): a control (n = 12, 0% DHA) diet or a DHA (n = 8, 0.9% DHA) diet. At 11 d, suckled pups from each dam were randomly assigned to a mucosal OT challenge: placebo or ovalbumin. At week 5, all pups systemically received ovalbumin + adjuvant to induce systemic immunization. At 21 d, pups from each dam were randomly assigned to 1 of the 2 diets for 21 d in a factorial design after which immune function and OT were assessed. RESULTS Feeding dams DHA during lactation resulted in a 40-60% higher splenocyte production of interleukin (IL)-10 when stimulated with concanavalin A, lipopolysaccharide (LPS), or ovalbumin and a 100% higher production of interferon (IFN)-γ with LPS (P < 0.05) than feeding the control diet to the pups. In comparison with pups fed the control diet, feeding DHA at weaning resulted in a 25% lower type 1 T helper (IL-1β) and type 2 T helper (IL-6) response by splenocytes after LPS stimulation and a 33% lower plasma concentration of ovalbumin-specific immunoglobulin (Ig) G (P < 0.05). Pups that did not receive additional DHA during the study had a 70% higher plasma concentration of ovalbumin-specific IgE than did the pups that received DHA at suckling and/or weaning (P < 0.05). CONCLUSIONS Feeding additional DHA during suckling had a beneficial programming effect on the ability of immune cells to produce IFN-γ and IL-10, and feeding DHA during weaning resulted in a lower inflammatory response. Providing no dietary DHA in either of the critical periods of immune development prevented the establishment of OT in female rat offspring.
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Affiliation(s)
- Caroline Richard
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Erin D Lewis
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Susan Goruk
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Catherine J Field
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
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Maturation of the Intestinal Epithelial Barrier in Neonatal Rats Coincides with Decreased FcRn Expression, Replacement of Vacuolated Enterocytes and Changed Blimp-1 Expression. PLoS One 2016; 11:e0164775. [PMID: 27736989 PMCID: PMC5063338 DOI: 10.1371/journal.pone.0164775] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 10/01/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The intestinal barrier is immature in newborn mammals allowing for transfer of bioactive macromolecules, e.g. protecting antibodies, from mother's milk to the blood circulation and in neonatal rodents lasts until weaning. This passage involves the neonatal-Fc-receptor (FcRn) binding IgG in the proximal and highly endocytic vacuolated enterocytes in the distal immature small intestine (SI). Recent studies have suggested an involvement of the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) in the regulation of SI maturation in mice. Hence, the objective of the present study was to monitor the development of the intestinal barrier function, in relation to Blimp-1 expression during both natural and precociously induced intestinal maturation in rats. RESULTS During the suckling period IgG plasma levels increased, while after gut closure it temporarily decreased. This corresponded to a high expression of FcRn in the proximal SI epithelium and the presence of vacuolated enterocytes in the distal SI. The immature foetal-type epithelium was replaced after weaning or induced precocious maturation, by an adult-type epithelium with FcRnneg cells in the proximal and by non-vacuolated enterocytes in the distal SI. In parallel to this epithelial shift, Blimp-1 expression decreased in the distal SI. CONCLUSION The switch from foetal- to adult-type epithelium, with decreased proximal expression of FcRn and distal replacement of vacuolated enterocytes, was concurrent in the two SI regions and could be used for monitoring SI maturation in the rat. The changes in expression of Blimp-1 in the distal SI epithelium followed the maturation pattern.
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The content of docosahexaenoic acid in the suckling and the weaning diet beneficially modulates the ability of immune cells to response to stimuli. J Nutr Biochem 2016; 35:22-29. [DOI: 10.1016/j.jnutbio.2016.05.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 04/28/2016] [Accepted: 05/26/2016] [Indexed: 12/15/2022]
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Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring. Br J Nutr 2016; 116:1001-12. [PMID: 27480608 DOI: 10.1017/s0007114516002919] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.
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Rigo-Adrover M, Saldaña-Ruíz S, van Limpt K, Knipping K, Garssen J, Knol J, Franch A, Castell M, Pérez-Cano FJ. A combination of scGOS/lcFOS with Bifidobacterium breve M-16V protects suckling rats from rotavirus gastroenteritis. Eur J Nutr 2016; 56:1657-1670. [PMID: 27112962 DOI: 10.1007/s00394-016-1213-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 03/31/2016] [Indexed: 12/17/2022]
Abstract
PURPOSE Rotavirus (RV) is the leading cause of severe diarrhoea among infants and young children, and although more standardized studies are needed, there is evidence that probiotics can help to fight against RV and other infectious and intestinal pathologies. On the other hand, the effects of prebiotics have not been properly addressed in the context of an RV infection. The aim of this study was to demonstrate a protective role for a specific scGOS/lcFOS 9:1 prebiotic mixture (PRE) separately, the probiotic Bifidobacterium breve M-16V (PRO) separately and the combination of the prebiotic mixture and the probiotic (synbiotic, SYN) in a suckling rat RV infection model. METHODS The animals received the intervention from the 3rd to the 21st day of life by oral gavage. On day 7, RV was orally administered. Clinical parameters and immune response were evaluated. RESULTS The intervention with the PRO reduced the incidence, severity and duration of the diarrhoea (p < 0.05). The PRE and SYN products improved clinical parameters as well, but a change in stool consistency induced by the PRE intervention hindered the observation of this effect. Both the PRE and the SYN, but not the PRO, significantly reduced viral shedding. All interventions modulated the specific antibody response in serum and intestinal washes at day 14 and 21 of life. CONCLUSIONS A daily supplement of a scGOS/lcFOS 9:1 prebiotic mixture, Bifidobacterium breve M-16V or a combination of both is highly effective in modulating RV-induced diarrhoea in this preclinical model.
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Affiliation(s)
- M Rigo-Adrover
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - S Saldaña-Ruíz
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | | | - K Knipping
- Nutricia Research, Utrecht, The Netherlands.,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - J Garssen
- Nutricia Research, Utrecht, The Netherlands.,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - J Knol
- Nutricia Research, Utrecht, The Netherlands
| | - A Franch
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - M Castell
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - F J Pérez-Cano
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain. .,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain.
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Woodward B. Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition. Int J Mol Sci 2016; 17:541. [PMID: 27077845 PMCID: PMC4848997 DOI: 10.3390/ijms17040541] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 04/05/2016] [Accepted: 04/06/2016] [Indexed: 11/16/2022] Open
Abstract
Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.
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Affiliation(s)
- Bill Woodward
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
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Lewis ED, Richard C, Goruk S, Dellschaft NS, Curtis JM, Jacobs RL, Field CJ. The Form of Choline in the Maternal Diet Affects Immune Development in Suckled Rat Offspring. J Nutr 2016; 146:823-30. [PMID: 26936140 DOI: 10.3945/jn.115.225888] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 01/14/2016] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Lipid-soluble phosphatidylcholine (PC) and aqueous free choline are absorbed and metabolized differently, but the metabolic effects of feeding these 2 forms of choline have not been thoroughly investigated. OBJECTIVE We sought to compare the effects of PC and free choline in the maternal diet on the development of the offspring's immune system. METHODS During lactation, Sprague-Dawley dams (n= 10) were randomly assigned to 1 of 2 diet groups containing the same concentration of total choline (1 g/kg diet) as free choline (choline bitartrate) or PC (egg lecithin). The splenocytes of pups aged 21 d were isolated and stimulated ex vivo with concanavalin A (ConA) or lipopolysaccharide (LPS), and the choline concentrations of stomach content, plasma, and the spleen were measured. RESULTS Pups from PC-fed dams had a lower proportion of cells involved in antigen presentation but produced 54% more interleukin (IL)-2, 163% more IL-6, and 107% more IFN-γ after ConA stimulation and 110% more IL-6 and 43% more tumor necrosis factor (TNF)-α after LPS stimulation (allP< 0.05). The PC concentrations were significantly higher in the plasma and spleen of pups from PC-fed dams (P< 0.05). Increasing the supply of PC in the form of lysophosphatidylcholine to splenocytes in vitro increased the rate of proliferation and IL-2 production and the surface expression of CD25, CD28, CD71, and CD152 on CD8+ T cells, suggesting 1 possible mechanism. CONCLUSIONS The results of this study demonstrate that providing choline to rats in the form of PC (compared to free choline), possibly by increasing the supply of PC to the suckling pups, promotes maturation and improves function of the offspring's immune system.
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Affiliation(s)
- Erin D Lewis
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
| | - Caroline Richard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
| | - Neele S Dellschaft
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and Early Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
| | - Jonathan M Curtis
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
| | - René L Jacobs
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and
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Griffiths PS, Walton C, Samsell L, Perez MK, Piedimonte G. Maternal high-fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring. Pediatr Res 2016; 79:278-86. [PMID: 26539661 PMCID: PMC4829879 DOI: 10.1038/pr.2015.226] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 08/08/2015] [Indexed: 01/21/2023]
Abstract
BACKGROUND We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. METHODS On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. RESULTS Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection. CONCLUSION Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition.
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Affiliation(s)
- Pamela S Griffiths
- Department of Pediatrics, West Virginia University, Morgantown, West Virginia
| | - Cheryl Walton
- Department of Pediatrics, West Virginia University, Morgantown, West Virginia
| | - Lennie Samsell
- Department of Pediatrics, West Virginia University, Morgantown, West Virginia
| | - Miriam K Perez
- Department of Community Pediatrics, The Cleveland Clinic, Cleveland, Ohio
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Richard C, Lewis ED, Goruk S, Field CJ. The content of docosahexaenoic acid in the maternal diet differentially affects the immune response in lactating dams and suckled offspring. Eur J Nutr 2015; 55:2255-64. [DOI: 10.1007/s00394-015-1035-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Accepted: 09/01/2015] [Indexed: 10/23/2022]
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Benoit B, Bruno J, Kayal F, Estienne M, Debard C, Ducroc R, Plaisancié P. Saturated and Unsaturated Fatty Acids Differently Modulate Colonic Goblet Cells In Vitro and in Rat Pups. J Nutr 2015; 145:1754-62. [PMID: 26108543 DOI: 10.3945/jn.115.211441] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 05/29/2015] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND High-fat diets induce intestinal barrier alterations and promote intestinal diseases. Little is known about the effects of long-chain fatty acids (LCFAs) on mucin 2 (MUC2) production by goblet cells, which are crucial for intestinal protection. OBJECTIVE We investigated the effects of LCFAs on the differentiation of colonic goblet cells, MUC2 expression, and colonic barrier function. METHODS Upon reaching confluence, human colonic mucus-secreting HT29-MTX cells were stimulated (21 d) with a saturated LCFA (palmitic or stearic acid), a monounsaturated LCFA (oleic acid), or a polyunsaturated LCFA (linoleic, γ-linolenic, α-linolenic, or eicosapentaenoic acid). In addition, rat pups underwent oral administration of oil (palm, rapeseed, or sunflower oil) or water (10 μL/g body weight, postnatal days 10-15). Subsequently, colon goblet cells were studied by Western blotting, reverse transcriptase-quantitative polymerase chain reaction, and immunohistochemistry and colonic transmucosal electrical resistance was measured by using Ussing chambers. RESULTS In vitro, palmitic acid enhanced MUC2 production (140% of control) and hepatocyte nuclear factor 4α expression, whereas oleic, linoleic, γ-linolenic, α-linolenic, and eicosapentaenoic acids reduced MUC2 expression (at least -50% of control). All unsaturated LCFAs decreased the expression of human atonal homolog 1, a transcription factor controlling goblet cell differentiation (at least -31% vs. control). In vivo, rats fed palm oil had higher palmitic acid concentrations (3-fold) in their colonic contents and increased mucus granule surfaces in their goblet cells (>2-fold) than did all other groups. Palm oil also increased colonic transmucosal electrical resistance (245% of control), yet had no effect on occludin and zonula occludens-1 expression. In contrast, sunflower and rapeseed oils decreased goblet cell number when compared with control (at least -10%) and palm oil (at least -14%) groups. CONCLUSIONS Palm oil in rat pups and palmitic acid in HT29-MTX cells increase the production of MUC2 and strengthen the intestinal barrier. In contrast, unsaturated LCFAs decrease MUC2 expression. These data should be taken into account in the context of preventive or therapeutic nutritional programs.
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Affiliation(s)
- Bérengère Benoit
- Lyon University, Villeurbanne, France; National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France
| | - Jérémie Bruno
- Lyon University, Villeurbanne, France; National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France
| | - Fanny Kayal
- Lyon University, Villeurbanne, France; National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France
| | - Monique Estienne
- National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France; National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France
| | - Cyrille Debard
- National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France; French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Oullins, France; and
| | - Robert Ducroc
- French Institute of Health and Medical Research U773, Bichat Beaujon Biomedical Research Centre, Paris, France
| | - Pascale Plaisancié
- National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France; National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France;
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Johnson SA, Javurek AB, Painter MS, Peritore MP, Ellersieck MR, Roberts RM, Rosenfeld CS. Disruption of parenting behaviors in california mice, a monogamous rodent species, by endocrine disrupting chemicals. PLoS One 2015; 10:e0126284. [PMID: 26039462 PMCID: PMC4454565 DOI: 10.1371/journal.pone.0126284] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2015] [Accepted: 03/31/2015] [Indexed: 12/31/2022] Open
Abstract
The nature and extent of care received by an infant can affect social, emotional and cognitive development, features that endure into adulthood. Here we employed the monogamous, California mouse (Peromyscus californicus), a species, like the human, where both parents invest in offspring care, to determine whether early exposure to endocrine disrupting chemicals (EDC: bisphenol A, BPA; ethinyl estradiol, EE) of one or both parents altered their behaviors towards their pups. Females exposed to either compound spent less time nursing, grooming and being associated with their pups than controls, although there was little consequence on their weight gain. Care of pups by males was less affected by exposure to BPA and EE, but control, non-exposed females appeared able to “sense” a male partner previously exposed to either compound and, as a consequence, reduced their own parental investment in offspring from such pairings. The data emphasize the potential vulnerability of pups born to parents that had been exposed during their own early development to EDC, and that effects on the male, although subtle, also have consequences on overall parental care due to lack of full acceptance of the male by the female partner.
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Affiliation(s)
- Sarah A. Johnson
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Biomedical Sciences, University of Missouri, Columbia, MO, 65211, United States of America
| | - Angela B. Javurek
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Biomedical Sciences, University of Missouri, Columbia, MO, 65211, United States of America
| | - Michele S. Painter
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Biomedical Sciences, University of Missouri, Columbia, MO, 65211, United States of America
| | - Michael P. Peritore
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Biomedical Sciences, University of Missouri, Columbia, MO, 65211, United States of America
| | - Mark R. Ellersieck
- Agriculture Experimental Station-Statistics, University of Missouri, Columbia, MO, 65211, United States of America
| | - R. Michael Roberts
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Animal Sciences, University of Missouri, Columbia, MO, 65211, United States of America
- Biochemistry, University of Missouri, Columbia, MO, 65211, United States of America
- Genetics Area Program, University of Missouri, Columbia, MO, 65211, United States of America
| | - Cheryl S. Rosenfeld
- Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, United States of America
- Biomedical Sciences, University of Missouri, Columbia, MO, 65211, United States of America
- Genetics Area Program, University of Missouri, Columbia, MO, 65211, United States of America
- * E-mail:
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Bar-Shira E, Cohen I, Elad O, Friedman A. Role of goblet cells and mucin layer in protecting maternal IgA in precocious birds. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2014; 44:186-194. [PMID: 24370536 DOI: 10.1016/j.dci.2013.12.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 12/14/2013] [Accepted: 12/15/2013] [Indexed: 06/03/2023]
Abstract
Immune protection of the gut in early life depends on provision of maternal antibodies, particularly that of IgA. In precocial birds (in this study Gallus gallus domesticus) the egg provides the only source of maternal antibodies, IgA inclusive. The gut-life of IgA in hatchlings is expected to be brief due to antigen binding and intestinal washout, and maternal IgA is likely to be depleted prior to immune independence at 7-10 days of age in the domestic fowl. We followed the track of maternal IgA in mucosal surfaces of the fowl and describe for the first time a mechanism that might provide the means to extend the active period of maternal IgA in the gut. Maternal IgA was located in the gut, lung, and cloacal bursa in embryos and hatchlings prior to the appearance of endogenic IgA positive plasma cells (D3 in the bursa or D7 in the gut and lung); the source of IgA was most probably the yolk, as the plasma was devoid of IgA till D7 post-hatch. The levels of maternal IgA decreased with time, but were still easily determined at the onset of endogenous IgA production following maturation of the adaptive immune system. Persistence of maternal IgA in the gut was enabled by goblet cell up-take by a yet un-described mechanism, and its consequent release in a mucin-like layer on enterocyte apical surfaces.
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Affiliation(s)
- Enav Bar-Shira
- Animal Sciences, R.H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel
| | - Inbal Cohen
- Animal Sciences, R.H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel
| | - Ori Elad
- Animal Sciences, R.H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel
| | - Aharon Friedman
- Animal Sciences, R.H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
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43
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Moussaoui N, Braniste V, Ait-Belgnaoui A, Gabanou M, Sekkal S, Olier M, Théodorou V, Martin PGP, Houdeau E. Changes in intestinal glucocorticoid sensitivity in early life shape the risk of epithelial barrier defect in maternal-deprived rats. PLoS One 2014; 9:e88382. [PMID: 24586321 PMCID: PMC3930527 DOI: 10.1371/journal.pone.0088382] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 01/06/2014] [Indexed: 12/17/2022] Open
Abstract
Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. Rat gut is immature at birth, and high intestinal GC sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of maternal separation (MS)-associated GC release in preterm babies, and whether GC sensitivity may shape MS effects in immature gut. A 4 hours-MS applied once at postnatal day (PND)10 enhanced plasma corticosterone in male and female pups, increased by two times the total in vivo intestinal permeability (IP) to oral FITC-Dextran 4 kDa (FD4) immediately after the end of MS, and induced bacterial translocation (BT) to liver and spleen. Ussing chamber experiments demonstrated a 2-fold increase of permeability to FD4 in the colon immediately after the end of MS, but not in the ileum. Colonic permeability was not only increased for FD4 but also to intact horseradish peroxidase 44 kDa in MS pups. In vivo, the glucocorticoid receptor (GR) antagonist RU486 or ML7 blockade of myosin light chain kinase controlling epithelial cytoskeleton contraction prevented MS-induced IP increase to oral FD4 and BT. In addition, the GR agonist dexamethasone dose-dependently mimicked MS-increase of IP to oral FD4. In contrast, MS effects on IP to oral FD4 and BT were absent at PND20, a model for full-term infant, characterized by a marked drop of IP to FD4 in response to dexamethasone, and decreased GR expression in the colon only compared to PND10 pups. These results show that high intestinal GC responsiveness in a rat model of prematurity defines a vulnerable window for a post-delivery MS, evoking immediate disruption of epithelial integrity in the large intestine, and increasing susceptibility to macromolecule passage and bacteremia.
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Affiliation(s)
- Nabila Moussaoui
- Intestinal Development, Xenobiotics & Immunotoxicology, Institut National de la Recherche Agronomique (INRA), Research Centre in Food Toxicology (Toxalim), Toulouse, France
- Integrative Toxicology & Metabolism, INRA, Toxalim, Toulouse, France
| | - Viorica Braniste
- Intestinal Development, Xenobiotics & Immunotoxicology, Institut National de la Recherche Agronomique (INRA), Research Centre in Food Toxicology (Toxalim), Toulouse, France
| | | | - Mélissa Gabanou
- Intestinal Development, Xenobiotics & Immunotoxicology, Institut National de la Recherche Agronomique (INRA), Research Centre in Food Toxicology (Toxalim), Toulouse, France
| | - Soraya Sekkal
- Neurogastroenterology & Nutrition, INRA, Toxalim, Toulouse, France
| | - Maiwenn Olier
- Neurogastroenterology & Nutrition, INRA, Toxalim, Toulouse, France
| | | | - Pascal G. P. Martin
- Integrative Toxicology & Metabolism, INRA, Toxalim, Toulouse, France
- GeT-TRiX facility, INRA, Toxalim, Toulouse, France
| | - Eric Houdeau
- Intestinal Development, Xenobiotics & Immunotoxicology, Institut National de la Recherche Agronomique (INRA), Research Centre in Food Toxicology (Toxalim), Toulouse, France
- * E-mail:
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