Dataset Information

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

ABSTRACT:

Background

Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis.

Methods

We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains.

Results

Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R² = 0.017, p = 0.001) and postnatal age (R² = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria.

Conclusions

Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants.

SUBMITTER: Heston SM

PROVIDER: S-EPMC10652614 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

Heston Sarah M SM Lim Charis Shu En CSE Ong Chengsi C Chua Mei Chien MC Kelly Matthew S MS Yeo Kee Thai KT

Gut pathogens 20231116 1

<h4>Background</h4>Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis.<h4>Methods</h4>We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota compositio ...[more]

PMID: 37974294

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Project description:BackgroundThe gastrointestinal (GI) microbiota has been linked to health consequences throughout life, from early life illnesses (e.g. sepsis and necrotising enterocolitis) to lifelong chronic conditions such as obesity and inflammatory bowel disease. It has also been observed that events in early life can lead to shifts in the microbiota, with some of these changes having been documented to persist into adulthood. A particularly extreme example of a divergent early GI microbiota occurs in premature neonates, who display a very different GI community to term infants. Certain characteristic patterns have been associated with negative health outcomes during the neonatal period, and these patterns may prove to have continual damaging effects if not resolved.ResultsIn this study we compared a set of premature infants with a paired set of term infants (n = 37 pairs) at 6 weeks of age and at 2 years of age. In the samples taken at 6 weeks of age we found microbial communities differing in both diversity and specific bacterial groups between the two infant cohorts. We identified clinical factors associated with over-abundance of potentially pathogenic organisms (e.g. Enterobacteriaceae) and reduced abundances of some beneficial organisms (e.g. Bifidobacterium). We contrasted these findings with samples taken at 2 years of age, which indicated that despite a very different initial gut microbiota, the two infant groups converged to a similar, more adult-like state. We identified clinical factors, including both prematurity and delivery method, which remain associated with components of the gut microbiota. Both clinical factors and microbial characteristics are compared to the occurrence of childhood wheeze and eczema, revealing associations between components of the GI microbiota and the development of these allergic conditions.ConclusionsThe faecal microbiota differs greatly between infants born at term and those born prematurely during early life, yet it converges over time. Despite this, early clinical factors remain significantly associated with the abundance of some bacterial groups at 2 years of age. Given the associations made between health conditions and the microbiota, factors that alter the makeup of the gut microbiota, and potentially its trajectory through life, could have important lifelong consequences.

Project description:The gut microbiome becomes shaped in the first days of life and continues to increase its diversity during the first months. Links between the configuration of the infant gut microbiome and infant health are being shown, but a comprehensive strain-level assessment of microbes vertically transmitted from mother to infant is still missing. We collected fecal and breast milk samples from multiple mother-infant pairs during the first year of life and applied shotgun metagenomic sequencing followed by computational strain-level profiling. We observed that several specific strains, including those of Bifidobacterium bifidum, Coprococcus comes, and Ruminococcus bromii, were present in samples from the same mother-infant pair, while being clearly distinct from those carried by other pairs, which is indicative of vertical transmission. We further applied metatranscriptomics to study the in vivo gene expression of vertically transmitted microbes and found that transmitted strains of Bacteroides and Bifidobacterium species were transcriptionally active in the guts of both adult and infant. By combining longitudinal microbiome sampling and newly developed computational tools for strain-level microbiome analysis, we demonstrated that it is possible to track the vertical transmission of microbial strains from mother to infants and to characterize their transcriptional activity. Our work provides the foundation for larger-scale surveys to identify the routes of vertical microbial transmission and its influence on postinfancy microbiome development. IMPORTANCE Early infant exposure is important in the acquisition and ultimate development of a healthy infant microbiome. There is increasing support for the idea that the maternal microbial reservoir is a key route of microbial transmission, and yet much is inferred from the observation of shared species in mother and infant. The presence of common species, per se, does not necessarily equate to vertical transmission, as species exhibit considerable strain heterogeneity. It is therefore imperative to assess whether shared microbes belong to the same genetic variant (i.e., strain) to support the hypothesis of vertical transmission. Here we demonstrate the potential of shotgun metagenomics and strain-level profiling to identify vertical transmission events. Combining these data with metatranscriptomics, we show that it is possible not only to identify and track the fate of microbes in the early infant microbiome but also to investigate the actively transcribing members of the community. These approaches will ultimately provide important insights into the acquisition, development, and community dynamics of the infant microbiome.

Dataset Information

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

Background

Methods

Results

Conclusions

Publications

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

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