Claire Bourlieu

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

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.

Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis

Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth.

Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion

Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donors human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label‐free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on “Pasteurization × Digestion time” interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β‐casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β‐casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p‐value = 1.4 E‐09), with β‐casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences.

Impact of homogenization of pasteurized human milk on gastric digestion in the preterm infant: A randomized controlled trial

BACKGROUND & AIMSnIt has been suggested that homogenization of Holder-pasteurized human milk (PHM) could improve fat absorption and weight gain in preterm infants, but the impact on the PHM digestive kinetics has never been studied. Our objective was to determine the impact of PHM homogenization on gastric digestion in preterm infants.nnnMETHODSnIn a randomized controlled trial, eight hospitalized tube-fed preterm infants were their own control to compare the gastric digestion of PHM and of homogenized PHM (PHHM). PHM was obtained from donors and, for half of it, was homogenized by ultrasonication. Over a six-day sequence, gastric aspirates were collected twice a day, before and 35, 60 or 90xa0min after the start of PHM or PHHM ingestion. The impact of homogenization on PHM digestive kinetics and disintegration was tested using a general linear mixed model. Results were expressed as meansxa0±xa0SD.nnnRESULTSnHomogenization leaded to a six-fold increase in the specific surface (Pxa0<xa00.01) of lipid droplets. The types of aggregates formed during digestion were different between PHM and PHHM, but the lipid fraction kept its initial structure all over the gastric digestion (native globules in PHM vs. blend of droplets in PHHM). Homogenization increased the gastric lipolysis level (Pxa0<xa00.01), particularly at 35 and 60xa0min (22 and 24% higher for PHHM, respectively). Homogenization enhanced the proteolysis of serum albumin (Pxa0<xa00.05) and reduced the meal emptying rate (Pxa0<xa00.001, half-time estimated at 30xa0min for PHM and 38xa0min for PHHM). The postprandial gastric pH was not affected (4.7xa0±xa00.9xa0at 90xa0min).nnnCONCLUSIONSnHomogenization of PHM increased the gastric lipolysis level. This could be a potential strategy to improve fat absorption, and thus growth and development in infants fed with PHM; however, its gastrointestinal tolerance needs to be investigated further. This trial was registered at clinicaltrials.gov as NCT02112331.

A first step towards a consensus static in vitro model for simulating full-term infant digestion

In vitro alternatives to clinical trials are used for studying human food digestion. For simulating infant digestion, only a few models, lacking physiological relevance, are available. Thanks to an extensive literature review of the in vivo infant digestive conditions, a gastrointestinal static in vitro model was developed for infants born at term and aged 28days. The model was applied to the digestion of a commercial infant formula. Kinetics of digestion, as well as the structural evolution, were compared with those obtained while submitting the same formula to the adult international consensus protocol of in vitro static digestion. The kinetics of proteolysis and lipolysis differed according to the physiological stage resulting mainly from the reduced level of enzymes and bile salts, as well as the higher gastric pH in the infant model. This in vitro static model of infant digestion is of interest for scientists, food or pharmaceutical manufacturers.

Polar lipid composition of bioactive dairy co-products buttermilk and butterserum: Emphasis on sphingolipid and ceramide isoforms

Bioactive lipids of the milk fat globule membrane become concentrated in two co-products of the butter industry, buttermilk and butterserum. Their lipid composition is detailed here with special emphasis on sphingolipid composition of nutritional interest, determined using GC, HPLC and tandem mass spectrometry. Butterserum was 2.5 times more concentrated in total fat than buttermilk, with 7.7±1.5vs 19.5±2.9wt% and even more concentrated in polar lipids, with 1.4±0.2vs 8.5±1.1wt%. Both ingredients constitute concentrated sources of sphingomyelin (3.4-21mg/g dry matter) and contained low amounts of bioactive ceramides in a ratio to sphingomyelin of 1:5mol% in buttermilk and 1:10mol% in butterserum. Compared to other natural lecithins, these two co-products are rich in long and saturated fatty acids (C22:0-C24:0), contain cholesterol and could have interesting applications in neonatal nutrition, but also as brain-protective, hepatoprotective and cholesterol lowering ingredients.

P320: Vers des formules infantiles mimant la structure et la digestion gastrique du lait maternel ?

Le lait maternel est l’aliment ideal pour le nouveau-ne (OMS). Quand l’allaitement n’est pas possible ou souhaite, des formules infantiles peuvent etre administrees. Alors que la composition nutritionnelle des formules infantiles a ete optimisee, peu de travaux se sont interesses a la structure de ces formules.[br/]nnQuel est l’impact de la structure des emulsions (formules infantiles, lait maternel) sur leurs cinetiques de digestion (lipolyse et proteolyse) et de destructuration?[br/]nnQuels sont les parametres cles affectant la digestion gastrique chez le nouveau-ne ?[br/]n[br/]nLes traitements technologiques modifient la structure des emulsions laitieres (agregation proteique, surface specifique des gouttelettes). Cette structure influe sur la destructuration de ces matrices et sur les cinetiques de lipolyse et proteolyse au cours de la digestion gastrique. La modulation des cinetiques d’hydrolyse en phase gastrique peut impacter sur les vitesses d’absorption des nutriments et ainsi moduler les reponses metaboliques. Il serait necessaire de developper des traitements technologiques doux pour la fabrication des formules infantiles, avec un impact minimum sur le globule gras, pour mimer au mieux la destructuration et l’hydrolyse des matrices natives.