Paper - Review

DOI: 10.1038/s41390-018-0022-z

Abstract

Background: Impact of (prematurity at birth) ← on premature infant gut microbiota

Methods: 1⃣ the effect of (gestational age) at birth & postnatal exposures ← on gut bacterial colonization in infants 2⃣ determined with 16S rDNA microbiome profiling

Results: 1⃣ Gut bacterial alpha-diversity differed ← between (premature & term infants) 2⃣ Alpha-diversity varied ← between (extremely premature & very premature infants)

Conclusion: (Gestational age at birth) & (early antibiotic exposure) → have significant effects

Introduction

Premature infants
→ have an immature gastrointestinal tract

Gut epithelium (← of premature infants)
→ has diminished barrier function
→ has increased permeability
∴ Translocation (← of bacteria) → from the gut → to the bloodstream
∴ 1⃣ Systemic inflammation 2⃣ Sepsis

❓: Premature infants ← has been hypothesized ← that antibiotic use
∵ infants' under-developed ← 1⃣ immune systems 2⃣ gut epithelia
∵ Promotes intestinal bacterial communities ← 1⃣ less diverse 2⃣ enriched with potential pathogens

Factors responsible
← altered (colonization patterns)
← observed in premature infants
→ are not well-defined

❗: aimed →
1⃣ to evaluate → how gut bacterial community structure varies → across the spectrum of gestational age at birth
2⃣ to assess → the effects of various exposures

Methods

Subject cohorts and inclusion criteria

Inclusion criteria
1⃣ appropriate size for gestational age
2⃣ <= 14 days of age ← at the time of enrollment
3⃣ NO ❌ major anomalies

Infant exposures

Data was collected → on the following exposures
1⃣ newborn antibiotic exposure
2⃣ delivery mode
3⃣ breastmilk exposure

Sample collection

Stool sample
→ were collected weekly

Sample sequencing and data analysis

V4-V5 hypervariable region
← of 16S ribosomal DNA
→ was performed using the Illumina MiSeq platform

Results

Sequencing

78 samples ← from 30 premature infants
189 samples ←from 176 term infants

Sequencing ← of these samples
→ resulted in total 22,012,483 reads for the 267

Bacterial alpha-diversity and abundance differences between premature and term infants

Bacterial alpha-diversity
← by Simpson's diversity index
→ varied throughout → the 6 weeks of life → for individual premature infants
→ with longitudinal stool samples

NO ❌ significant difference
← in the change in bacterial alpha-diversity
← between term & premature infants over time

Bacterial alpha-diversity
→ was NOT ❌ statistically significantly different
← between term & premature infants
← after adjusting for exposures

Differences ← in bacterial abundance
← between premature & term infants
→ were also assessed

NO ❌ statistically differences
← in bacterial abundance
← between premature and term infants

Hierarchical clustering

Hierarchical clustering
→ revealed that → premature infant samples clustered separately ← from term infant samples

Clustering was NOT ❌ statistically significant

Bacterial alpha-diversity and abundance differences at 6 weeks

The difference ← in bacterial alpha-diversity
→ was statistically significant
← at < 6 weeks of age
∴ Premature infants → having lower bacterial alpha-diversity ← than term infants

NO ❌ statistically significant differences
← in bacterial abundance
← in premature infants

Bacterial phylogenetic relatedness differences between premature and term infants

Bacterial phylogenetic relatedness differences
← between premature and term infants
→ were evaluated → at the 6-week time point
→ to address the more mature

Difference ← in phylogenetic relatedness
← between the two groups of infants
→ was not significant

Differences among premature infants by gestational age at birth

Divided the premature infants → into 3 groups
→ to test (the hypothesis) → that gut bacterial community structure varied → with degree of gestational immaturity at birth
1⃣ extremely premature infants 2⃣ very premature infants 3⃣ moderate-late premature infants

Differences ← in bacterial alpha-diversity
← 1⃣ between (extremely premature) & (moderate-late premature)
← 2⃣ between (extremely & very premature) infants

NO ❌ differences ← in bacterial alpha-diversity
← between (very & moderate-late) premature infants

Earlier gestational age at birth compared to later gestational age at birth

Divided the infants → into 2 groups
1⃣ who had an earlier gestational age at birth
2⃣ who had a later gestational age

Infants ← who born at a later gestational age
→ had greater abundance of → 1⃣ Streptococcus 2⃣ Bifidobacterium

Bacterial alpha-diversity
→ did NOT ❌ change differently over time
← between (earlier & later) GA infants

Bacterial alpha-diversity
→ remained distinct
← between (earlier & later) GA infants

NO ❌ apparent differences
← in bacterial alpha-diversity
→ after adjusting for exposures and age

Bacterial phylogenetic relatedness differences
← at 6 weeks
→ were not evident
← between moderate-late and term infants

NO ❌ other statistically significant differences
← in bacterial abundance
← between these two groups of infants

Analysis of corrected gestational age in premature infants

Bacterial alpha-diversity
→ appear to increase
← as corrected gestational age increases

Associations with exposures among premature infants

3 potential exposures
← thought to affect premature infant gut microbial structure
→ 1⃣ newborn antibiotic exposure 2⃣ delivery mode 3⃣ breastmilk exposure

None ← of the 3 exposures
→ had statistically significant independent effects
← on bacterial alpha-diversity

Evaluated
→ the effect of exposures & corrected gestational age
← on the abundance of the bacterial genera

Vaginal delivery
→ was associated with → greater Bacteroides abundance
Breastmilk exposure
→ was associated with → decreased abundance of Lactobacillus

Discussion

Differences ← in gut bacterial composition
← between premature & term infants
← in the first 6 weeks of life

Dominant taxa differ
← between premature & term infants

NO ❌ statistically significant differences
← in bacterial 1⃣ alpha-diversity 2⃣ abundance 3⃣ phylogenetic relatedness

NOT ❌ find → any significant effects
← on bacterial alpha-diversity & phylogenetic relatedness

(Extremely & very) preterm infants → clustered together
← after performing hierarchical clustering

Extremely premature infants
→ had significantly lower bacterial alpha-diversity
← compared to very premature & moderate-late premature infants

Gestational age ← at birth
→ has important associations ← with gut bacterial structure

Compared 1⃣ bacterial alpha-diversity 2⃣ phylogenetic relatedness
← between the moderate-late preterm infants & term infants

Differences ← in bacterial alpha-diversity
→ were identified

Potential benefit
← of probiotic supplementation
→ in (extremely & very) preterm infants

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