Log-contrast regression with functional compositional predictors: Linking preterm infants’ gut microbiome trajectories to neurobehavioral outcome

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

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Dichotomous development of the gut microbiome in preterm infants

Microbiome ◽

10.1186/s40168-018-0547-8 ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Thao T. B. Ho ◽

Maureen W. Groer ◽

Bradley Kane ◽

Alyson L. Yee ◽

Benjamin A. Torres ◽

...

Keyword(s):

Preterm Infants ◽

Gut Microbiome

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The gut microbiome of extremely preterm infants randomized to the early progression of enteral feeding

Pediatric Research ◽

10.1038/s41390-021-01831-w ◽

2021 ◽

Author(s):

Ariel A. Salas ◽

Kent A. Willis ◽

Waldemar A. Carlo ◽

Nengjun Yi ◽

Li Zhang ◽

...

Keyword(s):

Human Milk ◽

Microbial Diversity ◽

Preterm Infants ◽

Enteral Feeding ◽

Gut Microbiome ◽

Mode Of Delivery ◽

Early Feeding ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Early Progression

Abstract Background Early progression of feeding could influence the development of the gut microbiome. Methods We collected fecal samples from extremely preterm infants randomized to receive either early (feeding day 2) or delayed (feeding day 5) feeding progression. After study completion, we compared samples obtained at three different time points (week 1, week 2, and week 3) to determine longitudinal differences in specific taxa between the study groups using unadjusted and adjusted negative binomial and zero-inflated mixed models. Analyses were adjusted for a mode of delivery, breastmilk intake, and exposure to antibiotics. Results We analyzed 137 fecal samples from 51 infants. In unadjusted and adjusted analyses, we did not observe an early transition to higher microbial diversity within samples (i.e., alpha diversity) or significant differences in microbial diversity between samples (i.e., beta diversity) in the early feeding group. Our longitudinal, single-taxon analysis found consistent differences in the genera Lactococcus, Veillonella, and Bilophila between groups. Conclusions Differences in single-taxon analyses independent of the mode of delivery, exposure to antibiotics, and breastmilk feeding suggest potential benefits of early progression of enteral feeding volumes. However, this dietary intervention does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Trial Registration ClinicalTrials.gov identifier: NCT02915549. Impact Early progression of enteral feeding volumes with human milk reduces the duration of parenteral nutrition and the need for central venous access among extremely preterm infants. Early progression of enteral feeding leads to single-taxon differences in longitudinal analyses of the gut microbiome, but it does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Randomization in enteral feeding trials creates appealing opportunities to evaluate the effects of human milk diets on the gut microbiome.

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Joining the resistance

Science Translational Medicine ◽

10.1126/scitranslmed.aar7519 ◽

2018 ◽

Vol 10 (425) ◽

pp. eaar7519

Author(s):

Stephanie A. Christenson

Keyword(s):

Antibiotic Resistance ◽

Preterm Infants ◽

Resistance Genes ◽

Gut Microbiome ◽

Antibiotic Resistance Genes ◽

Antibiotic Administration ◽

Before And After

The effect of antibiotic resistance genes on the gut microbiome is examined in preterm infants before and after antibiotic administration.

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Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants

Clinical Infectious Diseases ◽

10.1093/cid/ciy882 ◽

2018 ◽

Vol 69 (2) ◽

pp. 268-277 ◽

Cited By ~ 21

Author(s):

S Graspeuntner ◽

S Waschina ◽

S Künzel ◽

N Twisselmann ◽

T K Rausch ◽

...

Keyword(s):

Preterm Infants ◽

Gut Microbiome ◽

Late Onset ◽

Anaerobic Bacteria ◽

Gene Profiling ◽

Rrna Gene ◽

Coagulase Negative Staphylococci ◽

Fermentation Products ◽

Gut Dysbiosis ◽

Late Onset Sepsis

Abstract Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

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The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

mSphere ◽

10.1128/msphere.00104-18 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 33

Author(s):

Stephen Wandro ◽

Stephanie Osborne ◽

Claudia Enriquez ◽

Christine Bixby ◽

Antonio Arrieta ◽

...

Keyword(s):

Health Outcomes ◽

Preterm Infant ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Gut Microbiome ◽

Infant Health ◽

Late Onset ◽

Bacterial Composition ◽

Fecal Samples ◽

Late Onset Sepsis

ABSTRACTThe assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficialBifidobacteriumspp. and were dominated byEnterobacteriaceae,Enterococcus, andStaphylococcusorganisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA]R2= 0.48,P< 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVAR2= 0.43,P< 0.001) and weakly associated with bacterial composition (Mantel statisticr= 0.23 ± 0.05,P< 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCEPreterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.

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616: ASSOCIATION OF GUT MICROBIOME AND EARLY REHOSPITALIZATION OF PRETERM INFANTS

Critical Care Medicine ◽

10.1097/01.ccm.0000808788.67905.0d ◽

2021 ◽

Vol 50 (1) ◽

pp. 300-300

Author(s):

Victoria Ronan ◽

Bingqing Xie ◽

Bree Andrews ◽

Erika Claud

Keyword(s):

Preterm Infants ◽

Gut Microbiome

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Effect of specific physiotherapy interventions in comparison with multisensory stimulation on neurobehavioral outcome and weight gain in preterm infants: a randomized control trial

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20175582 ◽

2017 ◽

Vol 5 (1) ◽

pp. 178

Author(s):

Unis D. Nadar ◽

Pareshkumar A. Thakkar ◽

Chaitali Shah

Keyword(s):

Weight Gain ◽

Preterm Infants ◽

Perinatal Asphyxia ◽

Statistical Tests ◽

Normal Brain ◽

Neurodevelopmental Outcomes ◽

Sensory Stimuli ◽

Multisensory Stimulation ◽

Physiotherapy Intervention ◽

Neurobehavioral Outcome

Background: A premature infant is deprived of in-utero sensory experiences which are essential for normal brain development and rather is exposed to unusual sensory stimuli in the Neonatal Intensive Care Units (NICU) that pose risk to the developing brain in terms of adverse neurodevelopmental outcomes. The objective of this study was to study and compare the effect of specific physiotherapy intervention with multisensory stimulation on neurobehavioral outcome and weight gain in preterm infants. Inclusion criteria was preterm infants appropriate for gestational age more than 32 weeks, babies who were hemodynamically stable and babies receiving full enteral feeds. Exclusion criteria were major congenital anomalies, inability to undergo intervention (any fracture) or perinatal asphyxia. Methods: Eligible infants were randomly allocated into one of the two groups. Group A was offered multisensory stimulation: Auditory, Tactile, Visual and Vestibular (ATVV). Group B received Specific Physiotherapy Intervention (SPI) in form of kinesthetic exercises, oil massage and oral stimulation. The outcome was studied before and after intervention. Appropriate statistical tests were applied. Results: Both the groups had better suck co-ordination and improvement on neurobehavioral scale following intervention when compared to pre-intervention status (P<0.0001). When both groups were compared, SPI group had better sucking coordination than ATVV group, improvement in neurobehavioral scale was similar in either group.Conclusions: In preterm infants, Specific Physiotherapy Interventions are more effective in improving suck co-ordination, has better weight gain and are equally effective in improving neurobehavioral outcome compared to multisensory stimulation.

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