Two human milk-like synthetic bacterial communities displayed contrasted impacts on barrier and immune responses in an intestinal quadricellular model.

The human milk (HM) microbiota, a highly diverse microbial ecosystem, is thought to contribute to the health benefits associated with breast-feeding, notably through its impact on infant gut microbiota. Our objective was to further explore the role of HM bacteria on gut homeostasis through a "disassembly/reassembly" strategy. HM strains covering the diversity of HM cultivable microbiota were first characterized individually and then assembled in synthetic bacterial communities (SynComs) using two human cellular models, peripheral blood mononuclear cells and a quadricellular model mimicking intestinal epithelium. Selected HM bacteria displayed a large range of immunomodulatory properties and had variable effects on epithelial barrier, allowing their classification in functional groups. This multispecies characterization of HM bacteria showed no clear association between taxonomy and HM bacteria impacts on epithelial immune and barrier functions, revealing the entirety and complexity of HM bacteria potential. More importantly, the assembly of HM strains into two SynComs of similar taxonomic composition but with strains exhibiting distinct individual properties, resulted in contrasting impacts on the epithelium. These impacts of SynComs partially diverged from the predicted ones based on individual bacteria. Overall, our results indicate that the functional properties of the HM bacterial community rather than the taxonomic composition itself could play a crucial role in intestinal homeostasis of infants.

Information and Parental Consent for French Neonatal Screening: A Qualitative Study on Parental Opinion.

Neonatal screening has excellent coverage in France. Data from the foreign literature raise questions about the informed consent to this screening. The Neonatal Screening and Informed Consent Dépistage Néonatal Information et Consentement Eclairé (DENICE) study was designed to assess whether information on neonatal screening provided for families in Brittany allows for informed consent. A qualitative methodology was chosen to collect parents' opinions on this topic. Twenty semi-structured interviews were conducted with twenty-seven parents whose children had positive neonatal screening for one of six diseases. The five main themes from the qualitative analysis were knowledge of neonatal screening, information received by parents, parental choice, the experience of the screening process, and parents' perspectives and wishes. Informed consent was weakened by parents' lack of knowledge regarding choice and the absence of a parent after birth. The study found that more information about screening during pregnancy would be preferable. The information should be repeated and accessible and should make it clear that neonatal screening is not mandatory, but informed consent should be obtained from parents who choose to screen their newborns.

Ileal Digestibility of Nitrogen and Amino Acids in Human Milk and an Infant Formula as Determined in Neonatal Minipiglets.

BACKGROUND: Infant formula (IF) has to provide at least the same amount of amino acids (AAs) as human milk (HM). AA digestibility in HM and IF was not studied extensively, with no data available for tryptophan digestibility. OBJECTIVES: The present study aimed to measure the true ileal digestibility (TID) of total nitrogen and AAs in HM and IF to estimate AA bioavailability using Yucatan mini-piglets as an infant model. METHODS: Twenty-four 19-day-old piglets (males and females) received either HM or IF for 6 days or a protein-free diet for 3 days, with cobalt-EDTA as an indigestible marker. Diets were fed hourly over 6 h before euthanasia and digesta collection. Total N, AA, and marker contents in diets and digesta were measured to determine the TID. Unidimensional statistical analyses were conducted. RESULTS: Dietary N content was not different between HM and IF, while true protein was lower in HM (-4 g/L) due to a 7-fold higher non-protein N content in HM. The TID of total N was lower (P < 0.001) for HM (91.3 ± 1.24%) than for IF (98.0 ± 0.810%), while the TID of amino acid nitrogen (AAN) was not different (average of 97.4 ± 0.655%, P = 0.272). HM and IF had similar (P > 0.05) TID for most of the AAs including tryptophan (96.7 ± 0.950%, P = 0.079), except for some AAs (lysine, phenylalanine, threonine, valine, alanine, proline, and serine), with small significant difference (P < 0.05). The first limiting AA was the aromatic AAs, and the digestible indispensable AA score (DIAAS) was higher for HM (DIAASHM = 101) than for IF (DIAASIF = 83). CONCLUSION: HM, compared to IF, had a lower TID for total N only, whereas the TID of AAN and most AAs, including Trp, was high and similar. A larger proportion of non-protein N is transferred to the microbiota with HM, which is of physiological relevance, although this fraction is poorly considered for IF manufacturing.

Infant nutrition affects the microbiota-gut-brain axis: Comparison of human milk vs. infant formula feeding in the piglet model.

Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow's milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.

New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants.

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.

Impact of early protein and energy intakes on neurodevelopment at 2 years of corrected age in very low birth weight infants: A single-center observational study.

INTRODUCTION: Aggressive nutritional strategy, particularly enhancing early provision of energy and protein, has appeared to reduce postnatal growth failure and improve later developmental outcomes. But the amount of macronutrients required remains unclear. The aim of this study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes. METHODS: This retrospective cohort study of very low birth weight infants born between January 2012 and December 2015 was conducted at one tertiary neonatal intensive care unit. The primary outcome was a neurodevelopmental impairment (NDI) at 2 years corrected age defined by a cerebral palsy or a 24 month Ages and Stages Questionnaires score on any of the five domains lower than 2 standard deviation below the mean score. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. RESULTS: Among 245 (73%) infants discharged home alive, 159 (65%) had follow-up at 2 years. Infants with NDI (55/159, 35%) were more likely male gender (67.3% versus 46.2%, P = 0.02) and experienced more patent ductus arteriosus (PDA) ligation (20% versus 5.8%, P = 0.01) than control. After adjusting for confounders, first-week protein intake (OR: 2.27 [CI: 1.07-5.14]; P < 0.05), second-week non-protein energy intake (OR: 1.03 [CI: 1.01-1.05]; P < 0.01) and PDA ligation (OR: 6.81 [1.80-28.46]; P < 0.01) had significant independent association with higher likelihood of NDI at 2 years. CONCLUSION: Providing nutrition above the optimal level may not be beneficial and may even be harmful. These results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines.

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

BACKGROUND & AIMS: It 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. METHODS: In 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 90 min 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 means ± SD. RESULTS: Homogenization leaded to a six-fold increase in the specific surface (P < 0.01) 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 (P < 0.01), particularly at 35 and 60 min (22 and 24% higher for PHHM, respectively). Homogenization enhanced the proteolysis of serum albumin (P < 0.05) and reduced the meal emptying rate (P < 0.001, half-time estimated at 30 min for PHM and 38 min for PHHM). The postprandial gastric pH was not affected (4.7 ± 0.9 at 90 min). CONCLUSIONS: Homogenization 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.

Impact of human milk pasteurization on gastric digestion in preterm infants: a randomized controlled trial.

BACKGROUND: Holder pasteurization has been reported to modify human milk composition and structure by inactivating bile salt-stimulated lipase (BSSL) and partially denaturing some of its proteins, potentially affecting its subsequent digestion. OBJECTIVE: We sought to determine the impact of human milk pasteurization on gastric digestion (particularly for proteins and lipids) in preterm infants who were fed their mothers' own milk either raw or pasteurized. DESIGN: In a randomized controlled trial, 12 hospitalized tube-fed preterm infants were their own control group in comparing the gastric digestion of raw human milk (RHM) with pasteurized human milk (PHM). Over a 6-d sequence, gastric aspirates were collected 2 times/d before and after RHM or PHM ingestion. The impact of milk pasteurization digestive kinetics and disintegration was tested with the use of a general linear mixed model. RESULTS: Despite inactivating BSSL, instantaneous lipolysis was not affected by pasteurization (mean ± SD at 90 min: 12.6% ± 4.7%; P > 0.05). Lipolysis occurred in milk before digestion and was higher for PHM than for RHM (mean ± SD: 3.2% ± 0.6% and 2.2% ± 0.8%, respectively; P < 0.001). Pasteurization enhanced the proteolysis of lactoferrin (P < 0.01) and reduced that of α-lactalbumin (only at 90 min) (P < 0.05). Strong emulsion destabilization was observed, with smaller aggregates and a higher specific surface for PHM (P < 0.05). Pasteurization did not affect gastric emptying (∼30-min half time) or pH (mean ± SD: 4.4 ± 0.8) at 90 min. CONCLUSIONS: Overall, pasteurization had no impact on the gastric digestion of lipids and some proteins from human milk but did affect lactoferrin and α-lactalbumin proteolysis and emulsion disintegration. Freeze-thawing and pasteurization increased the milk lipolysis before digestion but did not affect gastric lipolysis. Possible consequences on intestinal digestion and associated nutritional outcomes were not considered in this study. This trial was registered at clinicaltrials.gov as NCT02112331.

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.