Digestive-Absorptive Functions in Fetuses, Infants, and Children

Introduction

The developing gastrointestinal (GI) tract is the largest and most active immune organ of the body and supports important endocrine and exocrine roles in addition to its role for digestion. It encompasses a large mass of neural tissue that interacts closely with the developing central nervous system. In addition to intestinal tissue that is derived from the human sperm and egg, the intestinal microbiome is increasingly recognized as having a major role in development of the immune system, development of the brain, metabolism, and epigenetics. Fig. 86.1 depicts the myriad of integrated functions that transcend the digestive and absorptive role of the GI tract. The neonatal GI tract plays an important role in the pathogenesis of obesity, autoimmune diseases, allergy, and even neurodevelopmental disorders. In this chapter, we review the ontogeny and basic physiology of some of the major aspects of intestinal macronutrient (protein, carbohydrate, and lipid) digestion and absorption. The metabolic and immunologic aspects of the microbiome as related to digestion and absorption will be briefly discussed.

It is important to distinguish between the processes of digestion, absorption, and assimilation, with digestion primarily involving mechanisms that occur in the lumen of the intestine, absorption occurring at the intestinal mucosal surface, and assimilation occurring within and beyond the epithelial cells. A brief general overview of macronutrient digestion, absorption, and, where appropriate, assimilation is first provided and then the ontogeny of these processes will be presented during early fetal and postnatal life. Several of these descriptions of basic physiology will be augmented with clinically relevant correlations.

Intestinal Growth

Data accumulated by autopsy reports show the following small intestinal growth prenatally and postnatally: Mean length at 20 weeks gestation is 125 cm, at 30 weeks 200 cm, at term gestation 275 cm, at 1 year 380 cm, at 5 years 450 cm, at 10 years 500 cm, and at 20 years 575 cm. Although this growth, especially during fetal life, appears to be large, it belies the fact that the surface area of the intestine is growing much faster during this time. When one accounts for the total surface provided by the villi and microvilli, this surface area becomes the largest in the body, which is also exposed to an external environment that includes a vast variety of antigens, microbes, and foods. The major component of the intestinal barrier between the external environment and the interior consists of a single layer of intestinal epithelium.

The intestine is subdivided into five functional areas along the proximal-to-distal gradient: the small intestine comprises the duodenum, jejunum, and ileum; the large intestine encompasses the cecum and colon. Specialized cell and tissue types originating from all three germ layers are found: endoderm-derived epithelium includes specialized intestinal stem cells, smooth muscle, vascular, lymphatic and immune cells derived from mesoderm, and the enteric nervous system cells derived from ectoderm.

Intestinal Epithelial Cellular Diversity and Kinetics

The intestinal epithelium is comprised of a diverse population of cells that differ depending on the aboral gradient region that spans the mouth to the rectum. These cells also differ in function depending on what region of the GI tract they are located. The intestinal epithelium functions as a selective barrier by restricting microbes and other antigens to the gut lumen. The absorptive enterocyte along with cells of three secretory lineages comprise the epithelium. The epithelial cells of the intestine secrete digestive enzymes and mucus, absorb food particles, and produce hormones. The secretory cells involved in barrier function include goblet cells, which secrete mucin and Paneth cells, which release antimicrobial factors. The enteroendocrine cells secrete hormones involved in satiety, motility, secretion of digestive enzymes.

A crypt to villus gradient of cells is present wherein epithelial cells undergo mitosis in the crypt region. Most of these cells migrate along the villus to the tip, where they are eventually extruded into the lumen of the intestine. The turnover and migration time from cell production in the crypt to extrusion from the villus tip (“anoikis”) differs depending on age and region of the intestine, with younger animals showing longer migration times than adult animals. ^, Although most of the cells migrate to the villus tip, Paneth cells remain in the crypt region, where they perform the critical function of defending the mitotically active stem cells from pathogens using a myriad of defensive molecules. The different regions across the crypt to villus axes serve different functions. Cells of the crypt are highly proliferative, whereas cells in the mid to the upper villus become increasingly differentiated as they migrate to the villus tip for absorptive as well as immunologic and neuroendocrine functions.

General Aspects of Digestion, Absorption, and Assimilation

An overview of major digestive absorptive processes is provided in Fig. 86.2 . Food introduced into the mouth and stomach generally consists of large molecular aggregates that need to be further simplified by mechanical and biochemical means. However, milk presented to the newborn does not require chewing. Suck-swallow incoordination persists until 34 weeks gestational age, necessitating tube feeding. With tube feeding, digestive processes in the oral cavity are bypassed, and thus digestion begins in the stomach. Enzymatic and other chemical processes include interactions between the food and gastric acid, proteases, lipases, salivary- and pancreatic-derived carbohydrases, and emulsifiers such as bile acids. In addition to the digestive processes provided by the human host, microbes residing in various parts of the GI tract metabolize various foods, and the metabolites produced from these microbes may be further digested and absorbed by the human host. These metabolites can be used for energy production purposes such as occurs with the short-chain fatty acids and for various other metabolic processes such as with certain vitamins (e.g., vitamins K and B12).

Protein

Human and cow’s milk proteins comprise most of the proteins provided to the newborn infant, depending on whether the infant is breast- or formula-fed. Whey and casein synthesized in the mammary epithelial cells comprise the primary groups of milk proteins derived from these sources. Other protein components include immunoglobulins and albumin, which are not synthesized by the epithelial cells but rather are absorbed from the maternal blood or from plasma cells, which reside in the mammary tissue. Caseins can be separated from the whey fraction of milk using precipitation with the acid. This precipitation separates the supernatant whey fraction from the precipitate, which is the casein fraction. Both fractions contain important essential amino acids that are required for normal metabolic functions, growth, and development.

The processes for protein digestion are summarized in Box 86.1 and Fig. 86.2 . Digestion of proteins begins in the acidic environment of the stomach and continues in the small intestine under the influence of pancreatic proteases and peptidases. This process is accomplished by proteolytic cleavage of peptide bonds by enzymes that are secreted into the lumen of the upper digestive tract. In the stomach, pepsinogen is secreted and, in turn, is converted to the active protease pepsin by the action of acid. Secondly, the pancreas secretes proteases, such as trypsin, chymotrypsin, and carboxypeptidases, that require activation by the enzyme enterokinase; enterokinase is produced by the upper small intestinal epithelium, primarily in response to food. These proteases induce hydrolysis of the whole proteins within the lumen of the small intestine and result in the production of the medium to small amino acid chains called oligopeptides , dipeptides , or single amino acids .