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1.
Role of the microbiome in human development.
Dominguez-Bello, MG, Godoy-Vitorino, F, Knight, R, Blaser, MJ
Gut. 2019;(6):1108-1114
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Abstract
The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.
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The maternal microbiome during pregnancy and allergic disease in the offspring.
Vuillermin, PJ, Macia, L, Nanan, R, Tang, ML, Collier, F, Brix, S
Seminars in immunopathology. 2017;(6):669-675
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Abstract
There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring. The mechanisms by which the maternal microbiome influences the developing fetal immune system include alignment between the maternal and infant regulatory immune status and transplacental passage of microbial metabolites and IgG. Interplay between microbial stimulatory factors such as lipopolysaccharides and regulatory factors such as short-chain fatty acids may also influence on fetal immune development. However, our understanding of these pathways is at an early stage and further mechanistic studies are needed. There are also no data from human studies relating the composition and metabolic activity of the maternal microbiome during pregnancy to the offspring's immune status at birth and risk of allergic disease. Improved knowledge of these pathways may inform novel strategies for tackling the increase in allergic disorders in the modern world.
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From Birth to "Immunohealth," Allergies and Enterocolitis.
Houghteling, PD, Walker, WA
Journal of clinical gastroenterology. 2015;(0 1):S7-S12
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Abstract
Microbial signals stimulate development and maintenance of the neonatal immune system. The process begins in utero, with limited exposure to microbes in the intrauterine environment, as well as maternal immune signals priming the developing immune system. After birth and initial colonization, the immune system must be able to activate against pathogens, but also achieve oral tolerance of food and resident gut microbes. Through microbial signals and appropriate nutrition, the immune system is able to achieve homeostasis. Major challenges to successful colonization and immune system regulation include abnormal microbial inoculi (cesarean section, hygiene) and antibiotics. When normal colonization is interrupted, dysbiosis occurs. This imbalance of microbes and subsequently of the immune system can result in allergic diseases, asthma, or necrotizing enterocolitis. Probiotics and probiotic-derived therapies represent an exciting avenue to replete the population of commensal microbes and to prevent the immune-mediated sequelae of dysbiosis.
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Resource allocation in utero and health in later life.
Barker, DJ, Lampl, M, Roseboom, T, Winder, N
Placenta. 2012;:e30-4
Abstract
The way that a fetus obtains and allocates nutritional resources has profound consequences for its life-long health. Under the new developmental model for the origins of chronic disease, the causes to be identified are linked to normal variations in the processes of feto-placental development, that are associated with differences in the supply of nutrients to the baby. These differences programme the function of a few key systems that are linked to chronic disease, including the immune system, anti-oxidant defences, inflammation, and the number and quality of stem cells. There is not a separate cause for each different disease. Which chronic disease originates during development may depend more on timing than on qualitative differences in experience.
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Intestinal immune health.
Conroy, ME, Walker, WA
Nestle Nutrition workshop series. Paediatric programme. 2008;:111-21; discussion 121-5
Abstract
The fetal intestinal immune system is structurally intact from a very early gestational age. At birth, the neonate is challenged with an extraordinary and variable bacterial challenge. This mucosal and bacterial interface is the site of critical symbiotic and potentially pathogenic interactions. Neonatal inflammatory reactions are often exaggerated, creating a situation in a newly colonized gut whereby homeostasis must be actively achieved. Fortunately, the neonate is armed with a multitude of protective mechanisms by which to ensure a productive microbiota in the setting of an intact mucosal surface. The intestinal epithelium orchestrates complex interactions and signaling through a variety of intrinsic and extrinsic stimuli. Chief among these is the immunomodulatory capacity of breast milk which is increasingly implicated in the achievement of intestinal and immunologic health via a multitude of mechanisms. Additionally, developmental expression of enzymes, pattern recognition, downstream signaling and dendritic cell interaction all contribute to intestinal homeostasis. Current research is uncovering the molecular mechanisms behind many of these mechanisms. These strategies lend insight into the establishment of tolerance so critical to neonatal health. In a clinic context of increasing food allergy and inflammatory bowel disease, elucidating this machinery is increasingly pertinent. Future research should explore these molecular interactions more closely for their potential therapeutic applications.
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Impact of PUFA on early immune and fetal development.
Enke, U, Seyfarth, L, Schleussner, E, Markert, UR
The British journal of nutrition. 2008;(6):1158-68
Abstract
It has recently been reported that the increased prevalence in childhood allergy may be linked to deviations in fetal immune development. One reason may be impaired nutrient supply. Hence, a well-differentiated placenta together with an optimal fetal nutrition via the mother are important prerequisites for the establishment of a functional immune system with normal immune responses. Fatty acids and their derivatives can influence both the early immune development and immune maturation by regulating numerous metabolic processes and the gene expression of important proteins such as enzymes and cytokines. The present review summarises the impact of nutritional fatty acids on the development of the immune system as well as the fetal development. It describes the mechanisms of action of PUFA, trans fatty acids and conjugated linoleic acids in programming the fetus with regard to its risk of acquiring atopic diseases in childhood.