scholarly journals Human Milk-Based or Bovine Milk-Based Fortifiers Differentially Impact the Development of the Gut Microbiota of Preterm Infants

2021 ◽  
Vol 9 ◽  
Author(s):  
Miriam Aguilar-Lopez ◽  
Christine Wetzel ◽  
Alissa MacDonald ◽  
Thao T. B. Ho ◽  
Sharon M. Donovan

Background: Preterm infants are exposed to different dietary inputs during their hospitalization in the neonatal intensive care unit (NICU). These include human milk (HM), with a human milk-based (HMF) or a bovine milk-based (BMF) fortifier, or formula. Milk consumption and the type of fortification will cause changes in the gut microbiota structure of preterm infants. This study aimed to characterize the gut microbiota of PT infant according to the type of feeding and the type of HM fortification and its possible association with infant's growth.Methods: Ninety-seven infants born ≤33 wks of gestation or <1,500 g were followed during the hospitalization period in the NICU after birth until discharge. Clinical and dietary information was collected, including mode of delivery, pregnancy complications, mechanical ventilation, use of antibiotics, weight, and type and amount of milk consumed. To characterize the gut microbiota composition, weekly stool samples were collected from study participants. The V3–V4 region of the 16S rRNA bacterial gene was Sequenced using Illumina MiSeq technology.Results: After birth, black maternal race, corrected gestational age (GA) and exposure to pregnancy complications, had a significant effect on gut microbial diversity and the abundance of Enterococcus, Veillonella, Bifidobacterium, Enterobacter, and Bacteroides. Over the course of hospitalization, corrected GA and exposure to chorioamnionitis remained to have an effect on gut microbial composition. Two different enterotypes were found in the gut microbiota of preterm infants. One enriched in Escherichia-Shigella, and another enriched in uncharacterized Enterobacteriaceae, Klebsiella and Clostridium sensu stricto 1. Overall, HM and fortification with HMF were the most common feeding strategies. When consuming BMF, PT infants had higher growth rates than those consuming HMF. Milk and type of fortification were significantly associated with the abundance of Clostridium sensu stricto 1, Bifidobacterium and Lactobacillus.Conclusions: This observational study shows the significant association between milk consumption and the exposure to HMF or BMF fortification in the fecal microbiota composition of preterm infants. Additionally, these results show the effect of other perinatal factors in the establishment and development of PT infant's gut microbiota.

2021 ◽  
Vol 5 (1SP) ◽  
pp. 14
Author(s):  
Ariani Dewi Widodo

ABSTRACTBackground: Gut microbiota, a complex ecosystem consisting of abundant microorganisms, plays a role in preterm infants’ immunity, growth, and development. Dysbiosis or disruption of the gut microbiota can precipitate various diseases, such as allergy or autoimmune disorders in premature infants. Purpose: This study aimed to review gut microbiota in preterm infants and its role in supporting the infants’ immunity, growth, and development. Discussion: Bifidobactericeae is the predominant microbiota in GI tract of preterm infants. However, various factors can influence this gut microbiota e.g., genetics, lifestyle of the mothers (smoking, diet, use of antibiotic, obesity), birth mode, type of feeding, and environmental factors. Gut dysbiosis can result in impaired immune system which predisposes the preterm infants to infections, even fatal adverse event. Furthermore, the growth and development might be affected as well as lead to various neurodevelopmental and psychiatric disorders. Human milk is a prebiotic source which can stimulate the growth of Baifidobactericeae and Bacteroidetes. If the human milk is inadequate or unavailable, the recommended interventions for gut dysbiosis in premature infants are probiotics, prebiotics, or both supplementations (synbiotics). The administration of prebiotics and probiotics associates with lower morbidity and death rates in preterm infants, as well as shorter duration of hospital stay and duration to achieve full enteral feeding. Conclusions: Immunity as well as growth and development of preterm infants are affected greatly by gut microbiota The less diverse microbiota in preterm infants’ gut predispose them to various health problems. Hence, this problem should be managed properly, one of which is prebiotic and probiotic supplementation Keywords: Gastrointestinal Microbiome, Premature, Immunity, Growth, Development


2017 ◽  
Vol 106 (3) ◽  
pp. 821-830 ◽  
Author(s):  
Jean-Christophe Rozé ◽  
Pierre-Yves Ancel ◽  
Patricia Lepage ◽  
Laetitia Martin-Marchand ◽  
Ziad Al Nabhani ◽  
...  

2017 ◽  
Vol 8 (4) ◽  
pp. 563-567 ◽  
Author(s):  
J. Aakko ◽  
H. Kumar ◽  
S. Rautava ◽  
A. Wise ◽  
C. Autran ◽  
...  

Human milk oligosaccharides (HMOs) are structurally diverse unconjugated glycans with a composition unique to each lactating mother. While HMOs have been shown to have an impact on the development of infant gut microbiota, it is not well known if HMOs also already affect milk microbial composition. To address this question, we analysed eleven colostrum samples for HMO content by high-pressure liquid chromatography and microbiota composition by quantitative PCR. Higher total HMO concentration was associated with higher counts of Bifidobacterium spp. (ρ=0.63, P=0.036). A distinctive effect was seen when comparing different HMO groups: positive correlations were observed between sialylated HMOs and Bifidobacterium breve (ρ=0.84, P=0.001), and non-fucosylated/non-sialylated HMOs and Bifidobacterium longum group (ρ=0.65, P=0.030). In addition to associations between HMOs and bifidobacteria, positive correlations were observed between fucosylated HMOs and Akkermansia muciniphila (ρ=0.70, P=0.017), and between fucosylated/sialylated HMOs and Staphylococcus aureus (ρ=0.75, P=0.007). Our results suggest that the characterised HMOs have an effect on specific microbial groups in human milk. Both oligosaccharides and microbes provide a concise inoculum for the compositional development of the infant gut microbiota.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3836
Author(s):  
Cristina Iribarren ◽  
Maria K. Magnusson ◽  
Louise K. Vigsnæs ◽  
Imran Aziz ◽  
Ingvild Dybdrodt Amundsen ◽  
...  

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.


Author(s):  
Shan-Ming Chen ◽  
Ching-Pin Lin ◽  
Ming-Shiou Jan

Objective Bronchopulmonary dysplasia (BPD) is a complex chronic lung disease that primarily affects premature or critically ill infants. This pilot study investigated early changes in gut microbiota composition in BPD patients and explored the potential risk factors associated with these changes. Study Design Preterm infants admitted to our neonatal intensive care unit with a gestational age of 26 to 32 weeks were prospectively surveyed and eligible for stool collection on days 7 and 28 of postnatal age between February 2016 and June 2017. A 16S rRNA sequencing approach was applied to compare the gut microbiota composition between the BPD group and controls. Multiple linear regression analysis was used to identify the predictor variables. Results Eight subjects in the BPD group and 10 subjects in the preterm group were analyzed during the observation period. Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes were the four dominant bacteria phyla of intestinal microflora. A significantly lower diversity of gut microbiota was observed in the BPD group compared with the preterm group on day 28 (number of observed operational taxonomic units, p = 0.034; abundance-based coverage estimator, p = 0.022; Shannon index, p = 0.028). Multiple linear regression analysis revealed that high Neonatal Therapeutic Intervention Scoring System score (≧19) at 24 hours was statistically significant in predicting the proportion of aerobic with facultative anaerobic bacteria on day 28 (p = 0.002). Conclusion Infants with BPD are prone to develop gut dysbiosis in early life. A higher severity of illness and treatment intensity may indicate a higher risk of disrupting an anaerobic environment in the gut during the first month of life. Key Points


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Moira K Differding ◽  
Juliette Madan ◽  
Diane Gilbert-Diamond ◽  
Emily Baker ◽  
Margaret R Karagas ◽  
...  

Introduction: The prevalence of overweight and obesity in children ages 2-5 years continues to rise in the US. Experimental germ-free animal models indicate gut microbiota can cause excess weight gain. Observational human studies, mostly cross-sectional, also suggest gut microbiota is associated with obesity, but these studies have largely been conducted in older children and adults. Infants have a unique gut microbiota composition and function, under strong influence by human milk. Bifidobacteria, in particular, is hypothesized to be beneficial in the presence of human milk oligosaccharides. To our knowledge, no longitudinal studies have examined the association of the infant gut microbiota with childhood BMI, taking into account intake of human milk. Hypothesis: We hypothesized that infant gut microbiota composition, in particular relative abundance of Bifidobacteria, in the first year is prospectively associated with differences in child BMI from ages 2-5 years and associations are modified by duration of human milk feeding. Methods: We examined longitudinal data from mother-child dyads in the New Hampshire Birth Cohort, which began enrolling pregnant women from New Hampshire in 2009. We measured the infant gut microbiota using 16S rRNA sequencing at 6 weeks and 12 months of age. We estimated alpha diversity using the Shannon diversity index. Child BMI z scores (BMI-z) at 2-5 years of age were calculated using sex- and age-specific WHO growth charts. We used unadjusted and multivariable adjusted linear mixed models. We adjusted for pre-pregnancy BMI, birth weight, delivery mode, and infant BMI-z at 12 months (in 12-month microbiota models). We considered effect measure modification by breastfeeding duration. Results: Our analytic sample comprised 148 and 146 infants with microbiota data at 6 weeks and 12 months, respectively, and at least 1 BMI-z from ages 2-5 years. Shannon diversity at 6 weeks and 12 months of age, and top genera at 6 weeks were not significantly associated with child BMI-z. Abundance of 12-month Bifidobacterium was associated with lower BMI-z (-0.12; 95% CI (-0.25, 0.006)) and interacted with breastfeeding duration (p interaction <0.01); among infants consuming breast milk ≥6 months Bifidobacterium was associated with a 0.22 (95% CI: 0.06, 0.37) lower child BMI-z. Lower abundance of 12-month Prevotella , a bacteria linked to obesity in adults, was suggestively associated with lower child BMI-z and this association was also modified by breastfeeding duration (p interaction=0.01), such that it was only significant among infants breastfed < 6 months (0.34; 95% CI: 0.09, 0.60). Both interactions were consistent when breastfeeding duration was dichotomized at 12 months. Conclusion: Higher percent Bifidobacterium and lower Prevotella at 12 months was prospectively associated with lower childhood BMI-z, and both associations were modified by breastfeeding duration.


2021 ◽  
Vol 9 (9) ◽  
pp. 1939
Author(s):  
Shaillay Kumar Dogra ◽  
Francois-Pierre Martin ◽  
Dominique Donnicola ◽  
Monique Julita ◽  
Bernard Berger ◽  
...  

(1) Background: Human milk oligosaccharides (HMOs) may support immune protection, partly via their action on the early-life gut microbiota. Exploratory findings of a randomized placebo-controlled trial associated 2′fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) formula feeding with reduced risk for reported bronchitis and lower respiratory tract illnesses (LRTI), as well as changes in gut microbiota composition. We sought to identify putative gut microbial mechanisms linked with these clinical observations. (2) Methods: We used stool microbiota composition, metabolites including organic acids and gut health markers in several machine-learning-based classification tools related prospectively to experiencing reported bronchitis or LRTI, as compared to no reported respiratory illness. We performed preclinical epithelial barrier function modelling to add mechanistic insight to these clinical observations. (3) Results: Among the main features discriminant for infants who did not experience any reported bronchitis (n = 80/106) or LRTI (n = 70/103) were the 2-HMO formula containing 2′FL and LNnT, higher acetate, fucosylated glycans and Bifidobacterium, as well as lower succinate, butyrate, propionate and 5-aminovalerate, along with Carnobacteriaceae members and Escherichia. Acetate correlated with several Bifidobacterium species. By univariate analysis, infants experiencing no bronchitis or LRTI, compared with those who did, showed higher acetate (p < 0.007) and B. longum subsp. infantis (p ≤ 0.03). In vitro experiments demonstrate that 2′FL, LNnT and lacto-N-tetraose (LNT) stimulated B. longum subsp. infantis (ATCC15697) metabolic activity. Metabolites in spent culture media, primarily due to acetate, supported epithelial barrier protection. (4) Conclusions: An early-life gut ecology characterized by Bifidobacterium-species-driven metabolic changes partly explains the observed clinical outcomes of reduced risk for bronchitis and LRTI in infants fed a formula with HMOs. (Trial registry number NCT01715246.)


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3807
Author(s):  
Chiara Peila ◽  
Elena Spada ◽  
Sonia Deantoni ◽  
Ester Iuliano ◽  
Guido E. Moro ◽  
...  

Adequate nutrition is fundamental to neonatal survival and short-term outcomes, but it also has long-term consequences on quality of life and neurologic development of preterm infants. Donkey milk has been suggested as a valid alternative for children allergic to cows’ milk proteins, due to its biochemical similarity to human milk; we, hence, hypothesized that donkey milk could be a suitable basis for developing an innovative human milk fortifier for feeding preterm infants. The aim of the current study was to extend the findings and to evaluate the neurodevelopmental outcomes at 18 months of corrected age of the infants enrolled in the clinical trial named “Fortilat”. Infants born ≤1500 g and <32 weeks of gestational age were randomized to receive either a combination of bovine milk-based multicomponent fortifier and protein supplement or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The followed fortification protocol was the same for the two groups and the two diets were designed to be isoproteic and isocaloric. All infants enrolled were included in a developmental assessment program. The neurodevelopmental assessment was performed at 18 ± 6 months of corrected age. Minor and major neurodevelopmental impairment and General Quotient (GQ) at the Griffiths-II Mental Development Scale were considered. The GQ was considered both in continuous and as two classes: lower than and higher than (or equal to) a defined cutoff (GQcl). The difference in GQ and GQcl between the two arms was estimated using Mann–Whitney–Wilcoxon test or Fischer exact test, respectively, on the assumption of casual loss at follow-up. A further analysis was performed using generalized linear models. There were 103 children (bovine milk-derived fortifier arm = 54, donkey milk-derived fortifier arm = 49) included for the neurodevelopmental follow-up. All observations were included in the interval of 18 ± 6 months of corrected age. No significant difference was observed between the two arms in the incidence of neurologic sequelae and the GQs were similar in the two arms. Our results demonstrated no difference for the donkey milk-derived fortifier compared to standard bovine-derived fortifier regarding long-term neurodevelopmental outcomes.


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