Talk:BGDB Gastrointestinal - Postnatal

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BGD Internal Links 2009 6. Postnatal

The early settlers: intestinal microbiology in early life

Annu Rev Food Sci Technol. 2012;3:425-47. doi: 10.1146/annurev-food-022811-101120. Epub 2012 Jan 3.

Scholtens PA, Oozeer R, Martin R, Amor KB, Knol J. Source Danone Research, Centre for Specialised Nutrition, 6700 CA, Wageningen, Netherlands. petra.scholtens@danone.com

Abstract

The human intestinal microbiota forms an integral part of normal human physiology, and disturbances of the normal gut microbiology have been implicated in many health and disease issues. Because newborns are essentially sterile, their microbiota must establish and develop from the very first days of life. The first colonizers play an important role in the development of the ecosystem and may impact the long-term composition and activity of the microbiota. These first settlers obviously develop and proliferate dependent on host characteristics and diet, but other factors can also significantly contribute to this vital biological process. Considering the importance of the microbiota for the human immune, metabolic, and neurological systems, it is important to understand the dynamics and driving determinants of this development. This review gives a global overview of our current understanding of the different factors impacting the intestinal microbiology in early life.

PMID 22224552

http://www.annualreviews.org/doi/full/10.1146/annurev-food-022811-101120

Neural regulation of intestinal nutrient absorption

Prog Neurobiol. 2011 Oct;95(2):149-62. doi: 10.1016/j.pneurobio.2011.07.010. Epub 2011 Jul 27.

Mourad FH, Saadé NE. Source Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. fmourad@aub.edu.lb

Abstract

The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function. Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID 21854830

Trends Pharmacol Sci. 2011 Jul;32(7):402-9. doi: 10.1016/j.tips.2011.03.009. Epub 2011 Apr 29.

The translational value of rodent gastrointestinal functions: a cautionary tale

Sanger GJ, Holbrook JD, Andrews PL. Source Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 26 Ashfield Street, London, E1 2AJ, UK. g.sanger@qmul.ac.uk Abstract Understanding relationships between gene complements and physiology is important, especially where major species-dependent differences are apparent. Molecular and functional differences between rodents (rats, mice, guinea pigs) and humans are increasingly reported. Recently, the motilin gene, which encodes a gastrointestinal hormone widely detected in mammals, was found to be absent in rodents where the receptors are pseudogenes; however, actions of motilin in rodents are sometimes observed. Although ghrelin shares common ancestry with motilin, major species-dependent abberations are not reported. The apparently specific absence of functional motilin in rodents is associated with specialised digestive physiology, including loss of ability to vomit; motilin is functional in mammals capable of vomiting. The exception is rabbit, the only other mammal unable to vomit, in which motilin might be conserved to regulate caecotrophy, another specialised digestive process. Motilin illustrates a need for caution when translating animal functions to humans. Nevertheless, motilin receptor agonists are under development as gastroprokinetic drugs. Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID 21531468

Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation

Nutrition. 2011 Mar;27(3):269-75. doi: 10.1016/j.nut.2010.07.004. Epub 2010 Oct 13.

Yarandi SS, Hebbar G, Sauer CG, Cole CR, Ziegler TR. Source Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia, USA.

Abstract

OBJECTIVE: Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract. METHODS: Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract. Available abstracts were reviewed and more than 200 original articles were reviewed in detail. RESULTS: The available literature demonstrated that leptin can modulate several important functions of the gastrointestinal tract. Leptin interacts with the vagus nerve and cholecystokinin to delay gastric emptying and has a complex effect on motility of the small bowel. Leptin modulates absorption of macronutrients in the gastrointestinal tract differentially in physiologic and pathologic states. In physiologic states, exogenous leptin has been shown to decrease carbohydrate absorption and to increase the absorption of small peptides by the PepT1 di-/tripeptide transporter. In certain pathologic states, leptin has been shown to increase absorption of carbohydrates, proteins, and fat. Leptin has been shown to be upregulated in the colonic mucosa in patients with inflammatory bowel disease. Leptin stimulates gut mucosal cell proliferation and inhibits apoptosis. These functions have led to speculation about the role of leptin in tumorigenesis in the gastrointestinal tract, which is complicated by the multiple immunoregulatory effects of leptin. CONCLUSION: Leptin is an important modulator of major aspects of gastrointestinal tract functions, independent of its more well-described roles in appetite regulation and obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

Leptin

mainly produced by the gastric mucosa (as well as adipose tissue)
regulates motility of the stomach and small intestine through its interaction with CCK and the vagus nerve.
influences macronutrient transport in the small intestine in part by its action to regulate PepT1 and SGLT-1 transports of di-/tripeptides and glucose, respectively.

PMID 20947298

Ontogeny, growth and development of the small intestine: Understanding pediatric gastroenterology

World J Gastroenterol. 2010 Feb 21;16(7):787-99.

Drozdowski LA, Clandinin T, Thomson AB. Abstract Throughout our lifetime, the intestine changes. Some alterations in its form and function may be genetically determined, and some are the result of adaptation to diet, temperature, or stress. The critical period programming of the intestine can be modified, such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother, or in the diet of the weanlings. This early forced adaptation may persist in later life, such as the unwanted increased intestinal absorption of sugars, fatty acids and cholesterol. Thus, the ontogeny, early growth and development of the intestine is important for the adult gastroenterologist to appreciate, because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.

human small intestine at birth is morphologically and biochemically more mature than that of other mammals.
some of the brush border membrane (BBM) enzymatic maturation that occurs prenatally in humans only occurs after birth in rodents.
villus formation - is initiated at 9-10 wk gestation, and proceeds in a cranial-caudal direction.
intestinal crypts - then follows in humans, but in rodents, crypts do not develop until after birth.
cells of the intestinal mucosa - enterocytes, enteroendocrine cells, Paneth and goblet cells.
Liver - Bile acid luminal concentration and the bile acid pool are low in the preterm and term infant, and rise as the animal ages. (low levels associated with malabsorption of lipids)
human intestine - all epithelial cell types known to occur in the adult are present by the end of the first trimester.
Lactose disaccharide major carbohydrate in milk, cleaved by BBM lactase-phlorizin hydrolase (LPH) into glucose and galactose. LPH is therefore a crucial enzyme for neonates who are solely dependent on their mother’s milk for nourishment.

PMID 20143457

http://www.wjgnet.com/1007-9327/full/v16/i7/787.htm

Lipid digestion and absorption in early life: an update

Curr Opin Clin Nutr Metab Care. 2010 May;13(3):314-20. doi: 10.1097/MCO.0b013e328337bbf0.

Lindquist S, Hernell O. Source Department of Clinical Sciences/Pediatrics, Umeå University, Umeå, Sweden. susanne.lindquist@pediatri.umu.se

Abstract

PURPOSE OF REVIEW: To highlight our understanding of digestion and absorption of dietary lipids in newborn infants, and specifically how these processes differ from those in children and adults. RECENT FINDINGS: The intestinal concentration of pancreatic triglyceride lipase (PTL) and bile salts is lower in newborns compared to later in life. Instead the PTL-related protein 2 and bile salt-stimulated lipase (BSSL) are the key enzymes secreted from pancreas, which in concerted action with gastric lipase operate to achieve efficient fat absorption during infancy. BSSL is also present in human milk which affects fat absorption and growth in breast-fed preterm infants. Under conditions of low luminal bile salt concentrations fat absorption is likely to occur from liquid crystalline product phases, which may result in absorption from an extended part of the small intestinal mucosal surfaces compared to adults. Chylomicron assembly and secretion also seem to adapt to the specific situation of the newborn. SUMMARY: Both fat digestion and product absorption are different in newborn infants compared to adults; other lipases are used for digestion and different physical-chemical phases may be used for product absorption. Why these differences occur is still an unsolved question of considerable importance to neonatal nutrition.

PMID 20179589

Development of the human gastrointestinal tract: twenty years of progress

Gastroenterology. 1999 Mar;116(3):702-31.

Montgomery RK, Mulberg AE, Grand RJ. Source Division of Pediatric Gastroenterology and Nutrition, The Floating Hospital for Children at New England Medical Center, Boston, MA 02111-1533, USA.

Abstract

A combination of approaches has begun to elucidate the mechanisms of gastrointestinal development. This review describes progress over the last 20 years in understanding human gastrointestinal development, including data from both human and experimental animal studies that address molecular mechanisms. Rapid progress is being made in the identification of genes regulating gastrointestinal development. Genes directing initial formation of the endoderm as well as organ-specific patterning are beginning to be identified. Signaling pathways regulating the overall right-left asymmetry of the gastrointestinal tract and epithelial-mesenchymal interactions are being clarified. In searching for extrinsic developmental regulators, numerous candidate trophic factors have been proposed, but compelling evidence remains elusive. A critical gene that initiates pancreas development has been identified, as well as a number of genes regulating liver, stomach, and intestinal development. Mutations in genes affecting neural crest cell migration have been shown to give rise to Hirschsprung's disease. Considerable progress has been achieved in understanding specific phenomena, such as the transcription factors regulating expression of sucrase-isomaltase and fatty acid-binding protein. The challenge for the future is to integrate these data into a more complete understanding of the physiology of gastrointestinal development.

PMID 10029630

Host factors in amniotic fluid and breast milk that contribute to gut maturation

Clin Rev Allergy Immunol. 2008 Apr;34(2):191-204. doi: 10.1007/s12016-007-8032-3.

Wagner CL, Taylor SN, Johnson D. Source Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 173 Ashley Avenue, P.O. Box 250513, Charleston, SC 29425, USA. wagnercl@musc.edu Abstract The gut represents a complex organ system with regional differences, which reflect selective digestive and absorptive functions that change constantly in response to bodily requirements and the outside milieu. As a barrier to the external environment, gut epithelium must be renewed rapidly and repeatedly. Growth and renewal of gut epithelial cells is dependent on controlled cell stimulation and proliferation by a number of signaling processes and agents, including gut peptides-both endogenous and exogenous sources. This cascade of events begins during fetal development; with the ingestion of amniotic fluid, this process is enhanced and continued during infancy and early childhood through the ingestion of human milk. Events influenced by amniotic fluid during fetal development and those influenced by human milk that unfold after birth and early childhood to render the gut mature are presented. PMID 18330727

Development of the vertebrate small intestine and mechanisms of cell differentiation

Int J Dev Biol. 1990 Mar;34(1):205-18.

Dauça M, Bouziges F, Colin S, Kedinger M, Keller MK, Schilt J, Simon-Assmann P, Haffen K. Source Laboratoire de Biologie Cellulaire du Développement, Université de Nancy I, Vandoeuvre-les-Nancy, France.

Abstract

The intestinal epithelium represents an attractive biological model of differentiation from stem cells to highly differentiated epithelial cells, not only during particular developmental events depending upon the vertebrate species considered but also throughout adult life. The ontogenic maturation of the intestinal epithelium arises from both a programmed expression of specific genes and epigenetic influences mainly due to epithelial and mesenchymal interactions and hormonal participation. In the present paper we review the structural and functional changes that occur in the amphibian, avian and mammalian intestine during embryonic and/or post-embryonic development. Furthermore, we review the data concerning the mechanisms which control the cytodifferentiation of the intestinal epithelium. PMID 2203458

Antiinfective properties of human milk

J Nutr. 2008 Sep;138(9):1801S-1806S.

Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A.

Department of Neonatology and Neonatal Intensive Care, Spedali Civili, 25123 Brescia, Italy. gaechirico@alice.it Abstract The unfavorable effects of neonatal immunodeficiency are limited by some naturally occurring compensatory mechanisms, such as the introduction of protective and immunological components of human milk in the infant. Breast-feeding maintains the maternal-fetal immunological link after birth, may favor the transmission of immunocompetence from the mother to her infant, and is considered an important contributory factor to the neonatal immune defense system during a delicate and crucial period for immune development. Several studies have reported that breast-feeding, because of the antimicrobial activity against several viruses, bacteria, and protozoa, may reduce the incidence of infection in infants. The protection from infections may be ensured either passively by factors with antiinfective, hormonal, enzymatic, trophic, and bioactive activity present in breast milk, or through a modulator effect on the neonatal immune system exerted by cells, cytokines, and other immune agents in human milk.

PMID: 18716190 http://www.ncbi.nlm.nih.gov/pubmed/18716190

Reevaluation of the DHA requirement for the premature infant

Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):143-50. Epub 2009 Jul 5

Lapillonne A, Jensen CL.

APHP, Paris Descartes University, Paris, France. alexandre.lapillonne@svp.aphp.fr

Abstract

The long-chain polyunsaturated fatty acid (LC-PUFA) intake in preterm infants is crucial for normal central nervous system development and has the potential for long-lasting effects that extend beyond the period of dietary insufficiency. While much attention has focused on improving their nutritional intake, many premature infants do not receive an adequate DHA supply. We demonstrate that enterally fed premature infants exhibit daily DHA deficit of 20mg/kg.d, representing 44% of the DHA that should have been accumulated. Furthermore, the DHA content of human milk and current preterm formulas cannot compensate for an early DHA deficit which may occur during the first month of life. We recommend breast-feeding, which supplies preformed LC-PUFA, as the preferred method of feeding for preterm infants. However, to fulfill the specific DHA requirement of these infants, we recommend increasing the DHA content of human milk either by providing the mothers with a DHA supplement or by adding DHA directly to the milk. Increasing the DHA content above 1% total fatty acids appears to be safe and may enhance neurological development particularly that of infants with a birth weight below 1250 g. We estimate that human milk and preterm formula should contain approximately 1.5% of fatty acid as DHA to prevent the appearance of a DHA deficit and to compensate for the early DHA deficit.

LC-PUFA, particularly docosahexaenoic acid (DHA) and arachidonic acid (AA), accumulate rapidly during the brain growth spurt
During the last trimester of pregnancy, the placenta provides the fetus with AA and DHA.
highly concentrated in cell membranes of the retina and brain
have important effects on membrane function, neurogenesis, photoreceptor differentiation, activation of the visual pigment rhodopsin, protection against oxidative stress, the activity of several enzymes, the function of ion channels, and the levels and metabolism of neurotransmitters and eicosanoids

PMID: 19577914 http://www.ncbi.nlm.nih.gov/pubmed/19577914