Specificity of Infant Digestive Conditions: Some Clues for Developing Relevant In Vitro Models

Abstract

Digestion of nutrients is an essential function of the newborn infant gut to allow growth and development and understanding infant digestive function is essential to optimize nutrition and oral drug delivery. Ethical considerations prohibit invasive in vivo trials and as a consequence in vitro assays are often conducted. However, the choice of in vitro model parameters are not supported by an exhaustive analysis of the literature and do not mimic precisely the digestive conditions of the infant. This review contains a compilation of the studies which characterized the gastroduodenal conditions in full-term or preterm infants of variable postnatal age from birth up to six months. Important data about healthy full-term infants are reported. The enzymatic (type of enzymes and level of activity) and nonenzymatic (milk-based diet, frequency of feeding, bile salt concentrations) conditions of digestion in infants are shown to differ significantly from those in adults. In addition, the interindividual and developmental variability of the digestive conditions in infants is also highlighted.

Adsorption of gastric lipase onto multicomponent model lipid monolayers with phase separation

“…HGL has been called "extremophilic" as it is stable and active in the acid environment of the stomach, it is resistant to pepsin hydrolysis and it is not inhibited by the bile salts present in the gastro-intestinal tract [7]. Its optimum activity at acidic pH (4-5.4) on natural long chain TG emulsions [8] is unique among lipases and is explained by a better adsorption at the lipid/water interface at low pH [9,10] while, above neutral pH, [11] the enzyme remains in the water phase and is poorly stable [12]. The interfacial characterization of HGL or of close analogues such as dog gastric lipase (DGL, 86 % amino acid sequence identity with human GL) has been investigated using Langmuir films based on lipid homogeneous monolayers.…”

“…HGL is not only the first lipase found along the gastro-intestinal tract, it is also produced at high levels in the early life while the production of pancreatic enzymes and bile is still limited [12][13][14]. In the neonatal context, lipid digestion is crucial for cerebral and global development and growth, and HGL appears as a central enzyme in this process [12,14].…”

“…In the neonatal context, lipid digestion is crucial for cerebral and global development and growth, and HGL appears as a central enzyme in this process [12,14]. HGL is able to initiate the lipolysis of milk fat globules, what is not readily done by pancreatic lipase [15].…”

Towards infant formula biomimetic of human milk structure and digestive behaviour

“…Though several pertinent static in vitro digestion models mimicking the infant digestive conditions have been proposed (Dupont et al, 2010;Bouzerzour et al, 2012;Bourlieu et al, 2014;Levi et al, in press), very few studies have investigated the behaviour of HM during static in vitro digestion. Most digestion models were employed to evaluate IF digestion (Lueamsaisuk et al, 2014).…”

Approaches to Static Digestion Models

“…However, there have also been many studies of the breakdown of milk proteins in the infant gut. For a good review of the conditions pertaining to the infant gut there is a recent article by the Bourlieu et al ( 2014 ). This review gives a good idea of the physiological environment of the infant gut, both of premature and term infants.…”