The Role of Human Milk in Decreasing Necrotizing Enterocolitis Through Modulation of the Infant Gut Microbiome: A Scoping Review

2020 ◽  
Vol 36 (4) ◽  
pp. 647-656
Author(s):  
Jessica A. Davis ◽  
Kelley Baumgartel ◽  
Michael J. Morowitz ◽  
Vivianna Giangrasso ◽  
Jill R. Demirci
Keyword(s):  
Human Milk ◽  
Necrotizing Enterocolitis ◽  
Scoping Review ◽  
Gut Microbiome ◽  
Human Infants ◽  
Microbiome Composition ◽  
Infant Diet ◽  
Infant Gut Microbiome ◽  
State Of The Science

Background Necrotizing enterocolitis is associated with a high incidence of morbidity and mortality in premature infants. Human milk minimizes necrotizing enterocolitis risk, although the mechanism of protection is not thoroughly understood. Increasingly, dysbiosis of the infant gut microbiome, which is affected by infant diet, is hypothesized to play a role in necrotizing enterocolitis pathophysiology. Research aim The aim of this scoping review was to summarize the state of the science regarding the hypothesis that the gut microbiome composition is a mediator of the relationship between human milk and decreased incidence of necrotizing enterocolitis within a sample of human infants. Methods Electronic databases and reference lists were searched for peer-reviewed primary research articles addressing the link between human milk, gut microbiome composition, and subsequent incidence of necrotizing enterocolitis among human infants. Results A total of four studies met criteria for inclusion in this review. Of these, evidence supporting the link between human milk, gut microbiome composition, and necrotizing enterocolitis was found in two (50%) studies. Conclusion Some evidence linking all three variables is provided in this review. Given the small number of available studies, and the limitations of those studies, more research is urgently needed to thoroughly understand the protection against necrotizing enterocolitis gained through the provision of human milk.

scholarly journals Effect of Environmental Exposures on the Gut Microbiota from Early Infancy to Two Years of Age

2021 ◽  
Vol 9 (10) ◽  
pp. 2140
Author(s):  
Kameron Y. Sugino ◽  
Tengfei Ma ◽  
Nigel Paneth ◽  
Sarah S. Comstock
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Gut Microbiome ◽  
Linear Models ◽  
Antibiotic Use ◽  
Temporal Variations ◽  
Milk Intake ◽  
Microbiome Composition ◽  
Infant Gut Microbiome ◽  
Over Time

The gut microbiota undergoes rapid changes during infancy in response to early-life exposures. We have investigated how the infant gut bacterial community matures over time and how exposures such as human milk and antibiotic treatment alter gut microbiota development. We used the LonGP program to create predictive models to determine the contribution of exposures on infant gut bacterial abundances from one month to two years of age. These models indicate that infant antibiotic use, human milk intake, maternal pre-pregnancy BMI, and sample shipping time were associated with changes in gut microbiome composition. In most infants, Bacteroides, Lachnospiraceae unclassified, Faecalibacterium, Akkermansia, and Phascolarctobacterium abundance increased rapidly after 6 months, while Escherichia, Bifidobacterium, Veillonella, and Streptococcus decreased in abundance over time. Individual, time-varying, random effects explained most of the variation in the LonGP models. Multivariate association with linear models (MaAsLin) displayed partial agreement with LonGP in the predicted trajectories over time and in relation to significant factors such as human milk intake. Multiple factors influence the dynamic changes in bacterial composition of the infant gut. Within-individual differences dominate the temporal variations in the infant gut microbiome, suggesting individual temporal variability is an important feature to consider in studies with a longitudinal sampling design.

scholarly journals Infant gut microbiome composition is associated with non-social fear behavior in a pilot study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander L. Carlson ◽  
Kai Xia ◽  
M. Andrea Azcarate-Peril ◽  
Samuel P. Rosin ◽  
Jason P. Fine ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gut Microbiome ◽  
Brain Structures ◽  
Experimental Manipulation ◽  
Human Infant ◽  
Microbiome Composition ◽  
Social Fear ◽  
Infant Gut Microbiome ◽  
First Year Of Life ◽  
Fear Behavior

AbstractExperimental manipulation of gut microbes in animal models alters fear behavior and relevant neurocircuitry. In humans, the first year of life is a key period for brain development, the emergence of fearfulness, and the establishment of the gut microbiome. Variation in the infant gut microbiome has previously been linked to cognitive development, but its relationship with fear behavior and neurocircuitry is unknown. In this pilot study of 34 infants, we find that 1-year gut microbiome composition (Weighted Unifrac; lower abundance of Bacteroides, increased abundance of Veillonella, Dialister, and Clostridiales) is significantly associated with increased fear behavior during a non-social fear paradigm. Infants with increased richness and reduced evenness of the 1-month microbiome also display increased non-social fear. This study indicates associations of the human infant gut microbiome with fear behavior and possible relationships with fear-related brain structures on the basis of a small cohort. As such, it represents an important step in understanding the role of the gut microbiome in the development of human fear behaviors, but requires further validation with a larger number of participants.

scholarly journals The sugar composition of the fibre in selected plant foods modulates weaning infants’ gut microbiome composition and fermentation metabolites in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanthi G. Parkar ◽  
Jovyn K. T. Frost ◽  
Doug Rosendale ◽  
Halina M. Stoklosinski ◽  
Carel M. H. Jobsis ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Gas Production ◽  
Sugar Composition ◽  
Microbiome Composition ◽  
Fibre Concentration ◽  
Microbiome Profile ◽  
Infant Gut Microbiome ◽  
Immune Health ◽  
Faecal Bacteria

AbstractEight plant-based foods: oat flour and pureed apple, blackcurrant, carrot, gold- and green-fleshed kiwifruit, pumpkin, sweetcorn, were pre-digested and fermented with pooled inocula of weaning infants’ faecal bacteria in an in vitro hindgut model. Inulin and water were included as controls. The pre-digested foods were analysed for digestion-resistant fibre-derived sugar composition and standardised to the same total fibre concentration prior to fermentation. The food-microbiome interactions were then characterised by measuring microbial acid and gas metabolites, microbial glycosidase activity and determining microbiome structure. At the physiologically relevant time of 10 h of fermentation, the xyloglucan-rich apple and blackcurrant favoured a propiogenic metabolic and microbiome profile with no measurable gas production. Glucose-rich, xyloglucan-poor pumpkin caused the greatest increases in lactate and acetate (indicative of high fermentability) commensurate with increased bifidobacteria. Glucose-rich, xyloglucan-poor oats and sweetcorn, and arabinogalactan-rich carrot also increased lactate and acetate, and were more stimulatory of clostridial families, which are indicative of increased microbial diversity and gut and immune health. Inulin favoured a probiotic-driven consortium, while water supported a proteolytic microbiome. This study shows that the fibre-derived sugar composition of complementary foods may shape infant gut microbiome structure and metabolic activity, at least in vitro.

Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Daniela Paganini ◽  
Mary A Uyoga ◽  
Guus A M Kortman ◽  
Colin I Cercamondi ◽  
Hans C Winkler ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Community Dwelling ◽  
Controlled Study ◽  
Faecal Calprotectin ◽  
Microbiome Composition ◽  
E Coli ◽  
Increase Risk ◽  
Infant Gut Microbiome ◽  
Registration Number ◽  
Antibiotic Efficacy

ObjectiveMany African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).DesignIn a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8–10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (Fe−Ab+); (C) no antibiotics and iron-MNPs (Fe+Ab−); or (D) no antibiotics and no-iron-MNPs (Fe−Ab−). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5–D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.ResultsIn Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in Fe−Ab+. In Fe−Ab+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In Fe−Ab+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with Fe−Ab+ (12.4%) (p=0.04) and compared with Fe+Ab− (5.2%) (p=0.00).ConclusionOur findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.Trial registration numberNCT02118402; Pre-results.

scholarly journals Maximizing Nutrient Availability for the Breastfed Infant Through Colonization with B. Infantis EVC001 (FS04-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tracy Shafizadeh ◽  
Steve Frese ◽  
Giorgio Casaburi
Keyword(s):  
Human Milk ◽  
Nutrient Availability ◽  
Gut Microbiome ◽  
Bifidobacterium Longum ◽  
Developed Countries ◽  
Breastfed Infant ◽  
Control Group ◽  
Term Infants ◽  
Fecal Samples ◽  
Infant Gut Microbiome

Abstract Objectives Human breastmilk contains complete nutrient composition required for the developing infant, including human milk oligosaccharides (HMO). These complex carbohydrates are indigestible by the infant alone, and require digestion by gut microbes, namely Bifidobacterium longum subsp. infantis (B. infantis). However, decades of C-section delivery, formula feeding and increasing exposure to antibiotics have contributed the loss of this critical infant-associated gut bacterium in developed countries. Therefore, restoring B. infantis to the infant gut was hypothesized to improve the nutritional utilization of human breastmilk in healthy term infants. Methods In an open trial, healthy, exclusively breastfed term infants were fed 1.8 × 1010 CFU B. infantis EVC001 daily from day 7–27 postnatal (n = 34; EVC001-fed), or breastmilk alone (n = 32; control group). Fecal samples, milk samples, and weekly self-reported data were collected and analyzed for infant gut microbiome composition and function, human milk oligosaccharide composition, and fecal metabolites. 16S rRNA sequencing and shotgun metagenome sequencing provided characterization of microbial communities from birth through 60 days postnatal. Results Infants fed B. infantis EVC001 were uniformly colonized with this organism at 1011 CFU/g feces, while infants in the control group had a median total Bifidobacterium level below 10^5 CFU/g feces, despite exclusive breastfeeding. Mass spectrometry of fecal samples from B. infantis EVC001-fed infants showed that the resulting microbial community produced higher concentrations of lactate and acetate and lower excretion of HMO, while control infants showed significantly lower ability to capture and utilize these carbohydrates from human milk. Importantly, HMO content of breastmilk was not significantly different between groups and no difference was found in the gut microbiome of infants based on secretor status of mothers (presence or absence of 2’FL in breastmilk). Further, these changes were associated with reductions in taxa that have been associated with negative health outcomes including colic, asthma, eczema and allergy. Conclusions Overall, colonization with B. infantis is observed to be an effective way to restore maximal function of the infant gut microbiome to improve nutrient availability in the breastfed infant. Funding Sources This study was funded by Evolve BioSystems, Inc.

scholarly journals Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death

2008 ◽  
Vol 29 (1) ◽  
pp. 57-62 ◽  
Author(s):  
J Meinzen-Derr ◽  
◽  
B Poindexter ◽  
L Wrage ◽  
A L Morrow ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Human Milk ◽  
Necrotizing Enterocolitis ◽  
Extremely Low Birth Weight ◽  
Low Birth Weight Infants

scholarly journals The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3052
Author(s):  
Lila S. Nolan ◽  
Jamie M. Rimer ◽  
Misty Good
Keyword(s):  
Human Milk ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Mode Of Delivery ◽  
Intestinal Barrier ◽  
Vulnerable Population ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Intestinal Homeostasis

Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.

scholarly journals Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Steven A. Frese ◽  
Andra A. Hutton ◽  
Lindsey N. Contreras ◽  
Claire A. Shaw ◽  
Michelle C. Palumbo ◽  
...  
Keyword(s):  
Human Milk ◽  
Gut Microbiome ◽  
Bifidobacterium Longum ◽  
Specific Substrate ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Breastfed Infants ◽  
Gut Function ◽  
First Time

ABSTRACT The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function. Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

scholarly journals Delivery mode impacts newborn gut colonization efficiency

2020 ◽  
Author(s):  
Caroline Mitchell ◽  
Larson Hogstrom ◽  
Allison Bryant ◽  
Agnes Bergerat ◽  
Avital Cher ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Dominant Factor ◽  
Delivery Mode ◽  
Metagenomic Sequencing ◽  
Vaginal Microbiome ◽  
Abdominal Incision ◽  
Birth Canal ◽  
Microbiome Composition ◽  
Gut Colonization ◽  
Infant Gut Microbiome

AbstractDelivery mode is the variable with the greatest influence on the infant gut microbiome composition in the first few months of life. Children born by Cesarean section (C-section) lack species from the Bacteroides genus in their gut microbial community, and this difference can be detectable until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome, as children born by C-section do not pass through the birth canal; however, Bacteroides species are not common members of the vaginal microbiome, thus this explanation seems inadequate. Here, we set out to re-evaluate this hypothesis by collecting rectal and vaginal samples before delivery from 73 mothers with paired stool from their infants in the first two weeks of life. We compared microbial profiles of infants born by planned, pre-labor C-section to those born by emergent, post-labor surgery (where the child was in the birth canal, but eventually delivered through an abdominal incision), and found no significant differences in the microbiome between these two groups. Both groups showed the characteristic signature lack of Bacteroides species, despite their difference in exposure to the birth canal. Surprisingly, this signature was only evident in samples from week two of life, but not in the first week. Children born by C-section often had high abundance of Bacteroides in their first few days of life, but these were not stable colonizers of the infant gut, as they were not detectable by week two. Finally, we used metagenomic sequencing to compare microbial strains in maternal vaginal and rectal samples and samples from their infants; we found evidence for mother-to-child transmission of rectal rather than vaginal strains. These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.

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