The small intestinal brush border enzymes catalyse hydrolysis of oligosaccharides and disaccharides to glucose. They are considered as two complexes, sucrase-isomaltase and glucoamylase-maltase, with differing specificities for α-1,4 or α-1,6 bonds and for oligosaccharides of different sizes (34). Glucoamylase-maltase has a maximal affinity for straight-chain glucose polymers of between five and nine residues (35). Sucrase-isomaltase has maximal activity against maltose and maltotriose, as well as α-1,6 bonds (34). Enzyme activity is detectable in fetal life (36-39,40) with a marked third trimester increase such that at birth their activity is comparable with that of adults (41,42). In the early months of postnatal life, glucoamylase-maltase may help compensate for the physiological lower concentrations of pancreatic α-amylase if an infant is fed starch at this age (43).
Dietary starches may increase the concentration of pancreatic α-amylase. Higher duodenal concentrations of amylase in term and preterm infants were found in response to starch (26), but the difference in concentrations before and after ingestion were negligible in comparison with concentrations in older children. In functional studies there are discrepant results. Shulman et al. (44) found greater absorption of glucose polymers with age and increased duration of feeding. Senterre (45), however, found no increased absorption of starch after prolonged administration in low-birth-weight infants. The two studies used similar subjects but different techniques, making direct comparisons difficult. There appear to be no published studies regarding the induction of salivary amylase or glucoamylase by dietary starch.
A late gestational maturation of glucose transport is suggested by a review of several glucose perfusion studies (46). Glucose transport in the newborn small intestine per unit length is a quarter that in adults (47). This is probably the result of a relatively small mucosal surface area, less glucose transporters, or limited active transport capacity. However, this does not appear to be a rate-limiting process, nor is there evidence that starch or oligosaccharides can be transferred across the intestinal mucosa during the immediate neonatal period when the gut is more permeable to some molecules (48)
Endogenous bacteria in the large intestine, principally in the proximal colon where substrate availability is highest may ferment carbohydrate that escapes digestion and absorption in the small intestine. Many nutrients reaching the colon can be substrates for fermentation, but of these, starch and dietary fibre (nonstarch polysaccharide) are thought to be of most biologic significance.
The adult colonic flora is a stable population of up to 400 different bacterial species (49). During infancy, there is a continuous evolution of the bacterial flora (50), influenced initially by the type of milk fed. A difference is first evident between the faecal bacteria of breast- and formula-fed infants by 7 days, with significantly greater counts of Bacteroides fragilis isolated from the stools of the latter (51). Later, the flora of breast-fed babies contains less facultative anaerobes and more lactobacilli and bifidobacteria (52,53), in particular the bifidobacterial species Bifidobacterium longum and B. adolescentis (54). Weaning introduces starch and other novel food-stuffs that are less digested in the small intestine, resulting in further changes to the colonic environment that favour the development of an adult-type flora. The microflora of breast-fed infants is more immature, and there is an increase in certain anaerobic species such as Bacteroides after the introduction of a diet containing starch, oligossacharides, dietary fibre, and pathogens (55). This may account for the vulnerable period soon after the cessation of breast-feeding when infants are more susceptible to dehydrating diarrhoea (56), quite apart from the risk they face from contaminated complementary food (57).
The products of fermentation include gases (hydrogen, carbon dioxide, and methane), lactate, and short-chain fatty acids (SCFA). Because the colon is the home of such a multitude of diverse and interdependent bacterial species, it is at present impossible to identify the contribution of each to the fermentation reactions taking place. The principal polysaccharide-degrading bacteria are Bacteroides spp (58) although bifidobacteria, more common in the infant colon, are also capable of degrading polysaccharides (59).
The main SCFAs produced by colonic fermentation are acetic, propionic, and butyric. Most studies have been conducted in adults in whom it has been calculated that SCFAs are usually generated in the respective molar ratio of 60:20:18 (60). Both direct measurements of SCFA from dialysis bags in vivo (61) and estimates of SCFA production in the colon, in combination with measurement of their faecal concentrations (62), show that they are rapidly and well absorbed in the human colon, probably in their nonionised form by concentration-dependent passive diffusion (63).
Butyrate has been shown to be a preferential fuel for colonic epithelial cells in adults (64,65), although much less is detected in infant faeces (66). Significant amounts of propionate and acetate are transported to the liver, where they may be oxidised or used for gluconeogenesis (propionate) or the synthesis of long-chain fatty acids (acetate). Almost all propionate and butyrate reaching the liver is utilised there, but acetate can be further transported and utilised in peripheral tissues, such as muscle (67).
A small but significant amount of energy is gained by the colonic absorption of SCFA. In animal studies the partial utilisation of SCFAs has been shown to be 82% from intracaecal infusions, and most of it is retained as fat (68). In adult humans the energy is estimated to be approximately 2 kcal/g of nonabsorbable carbohydrate (69) or a contribution of 5% to 10% of energy requirements (70,71). Kien et al. (72) estimated that 24% to 74% of lactose may be converted into acetate in preterm infants with a potential 30% loss in adenosine triphosphate (73), but there appear to be no data on energy salvage from fermentation of starch in infancy at a time when the limited digestive capacity of the small intestine means that more starch will pass undigested into the colon.
Studies of the effects of SCFAs have been carried out almost exclusively in animals or in adult humans in whom some properties are related to all the SCFAs and some attributed to specific ones (74,75). All SCFAs appear to have trophic effects on the gastrointestinal mucosa, both in the upper and lower gut (64,67,76,77). Butyrate is the preferred fuel for colonocyte metabolism (64,78) and may protect against colonic cancer (79), although this may not happen at physiological concentrations (80). Propionate has been associated with cholesterol-lowering effects (81,82). Basal levels of insulin and glucagon are suppressed by increased loads of SCFA in ruminants (83), and although their metabolism differs considerably from that of humans, similar increases in insulin sensitivity have been demonstrated in humans (84). Insulin has anabolic effects in the human infant, and it is possible that by this means, starch fermentation may indirectly influence growth (73).
Bacterial populations and diet influence fermentation products. Different components of the diet encourage the growth of particular bacterial species. The faecal flora of formula-fed infants produce more propionate than that of breast-fed infants (85). Fermentation reactions are directly affected by the substrate; for example, butyrate is preferentially produced by the fermentation of resistant starch (86,87). The capacity of infants to ferment complex carbohydrates does not increase significantly until 7 to 9 months (88). In infants before weaning, fermentation products are mainly acetate with small amounts of propionate and n-butyrate. By 9 months the mean faecal concentrations of acetate, propionate and n-butyrate are as high or higher than adult values (88).
The net effect of the fermentation of polysaccharides to SCFA is an increase in the osmotic load within the colon, although unfermented, resistant starch itself causes an increased osmotic load. If the capacity for SCFA absorption is limited, then diarrhoea results, but in young piglets the presence of SCFA in the colon enhances water and sodium absorption (89). Absorption of SCFA from the colon of adults is rapid, and more than half of 14C-labelled SCFA appears in the breath within 6 hours (90). Lifschitz et al. (91) demonstrated that colonic acetate absorption in malnourished infants increases with age, but there are few other human studies of the development of colonic absorption of SCFA.
Various methods have been used to measure the digestion and absorption of starches in early life. These include measurement of blood glucose, balance studies, and the use of 13C stable isotope breath tests. Studies have been mainly performed in infants aged 1 month or less, often born prematurely, whose formulas contain glucose polymers to increase energy content. There is a glycaemic response after the ingestion of corn starch (92), glucose polymers (93), and lactose in term and preterm (94) infants. By measuring the intake of starch and the amount of residual starch in faeces, investigators have attempted to draw conclusions about whole-gut digestion with conflicting results (17,95). Such studies require meticulous measurements and do not usually take into account losses from methane and CO2 production. Results of total gut balance studies show that the individual contributions of upper and lower gut to starch digestion cannot be distinguished.
Calculations of intake and stool carbohydrate output are made easier by the use of starches enriched with the stable isotope 13C, but inconsistencies in results of balance studies have suggested a potential confounding effect from the excretion of bacterially derived carbohydrate, either contained within the cell walls or as fermentation product (96,97). Concomitant measurement of breath hydrogen allows estimation of the amount of starch that reaches the colon. Hydrogen is a bacterial fermentative product and cannot be produced by mammalian cells. The hydrogen breath test has been used in young infants to investigate the fermentation of lactose (98), although it may be difficult to use quantitatively (99), particularly in young infants (100). Shulman et al. (101) used it semiquantitatively to measure the utilisation of corn cereal in young infants, including information on the site of utilisation. Although young infants clearly possess the functional capacity to digest starch, this may be associated with a relatively decreased absorption of energy and nitrogen (102), highlighting the limitations of studying the digestion of a single nutrient alone.
There is much still to be learned about the ontogeny of the gastrointestinal tract during the weaning period and its capacity to make use of dietary starch. Existing work has focused mainly on the site or mechanism of starch digestion, but there is plainly a need to define the contributions of the small and large intestines and to quantify the various fates of different starches in infants of different ages.
This biotechnology enables the use of mathematical models to analyse whole-gut starch digestion curves. Mathematical models have been used in gastric emptying studies (107), adapting an equation that forms the basis of the χ2 distribution. Assumptions about curve interpretation would be strengthened if a gold standard for colonic absorption could be found. There is some hope that lactose-ureide, a synthetic condensation product of lactose and 13C-labelled urea, which resists breakdown by small intestinal enzymes (108), may provide such a standard.
Another way of quantifying the colonic fate of starch is by stoichiometry-calculation of the numerical relationship between the molecular species entering a chemical reaction and the amount and type of molecules produced. Stoichiometric equations for carbohydrate have been produced for adult humans and ruminant animals (69,109), based on known proportions of SCFAs in faeces and known production of carbon dioxide and methane. From these, the energy derived from fermentation reactions can be calculated: 34.5 C6H12O6 → 48 acetate + 11 propionate + 5 butyrate + 23.75 CH4 + 34.25 CO2 + 10.5 H2O
Energy calculations have been made on the whole gut by balance studies, separating the carbohydrate from the fat and protein component of stool and then calculating carbohydrate energy absorption (102,110). An attempt to quantify energy absorption by site of digestion was made for lactose using a stable isotope dilution method to measure the rate of entry of acetate into the peripheral circulation (72), and from the results, energy uptake was estimated from known thermal losses of potential adenosine triphosphate (110). The results show wide variability. A more complex whole-gut model could be developed by combining stoichiometry from fermentation models with data from stable isotope breath tests, and carbohydrate energy source quantified for infants of different ages.
Energy from SCFA produced as a result of colonic fermentation of starches is variously considered as loss (111) or gain, as though the infant small intestine were an inefficiently functioning organ (73,110). However, the small intestinal digestion and colonic fermentation that occur in the infant are interrelated physiological processes that together ensure efficient overall gut function. The need to understand the individual proportions of carbohydrate energy derived from small intestine and colon is underlined by observations that SCFA may have important effects on energy balance and growth by influencing insulin concentrations (73).
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