Acquisition and Development of the Infant Oral Bacteriome and Virome

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2024-03

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Abstract

Objective: The human microbiome is a collection of all the microscopic organisms such as bacteria, archaea, protists, fungi, and viruses that reside on or within the human being. This microbiome is comprised of many sub-microbiomes such as the skin, gut, vaginal, and oral. Each of these microbiomes is a complex and dynamic system that is affected by environmental disturbances such as antibiotic use, smoking, and systemic disease. Despite the significant body of research within the human microbiome project, knowledge gaps remain for acquisition and early development of the oral microbiome. Based on previous findings, at least 45% of adult oral microbiome is established within the first two years of life. We hypothesized that maternal habits play a critical role in shaping the infant oral microbiome. Methods: Buccal swabs were collected from 37 women (healthy, natal antibiotic user, and smokers) and their infants over a 15-month period at five time points: third trimester of pregnancy, 4-6 weeks, 4 months, 8 months, and 1 year after birth. DNA was isolated and underwent whole genome shotgun sequencing. Multiple bioinformatic tools were used to analyze the sequencing data: FragGeneScan, DIAMOND, and MEGAN were used to read, translate, and determine gene identity and function as indicated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the Comprehensive Antibiotic Resistance Database (CARD), and the Virulence Factor Database (VFDB). Virsorter2, DeepVirFinder, and Vibrant identified viral content. SourceTracker determined the contribution of the maternal biome to the babybiome. Results: SourceTracker revealed that the mother is the source of, on average, 83-92% of the bacteriome and 97% of the functional potential. This transmissibility was neither affected by the mother’s health status nor gestational experiences. Of bacteria that were transmitted 20-76% persisted in the infants over the first year of life. Some are known to be important contributors to periodontal disease such as Prevotella and Fusobacterium nucleatum. Children born to mothers given antibiotics during delivery had bacteria that demonstrated high levels of antibiotic resistance genes. On average, 87% of the antibiotic resistance genes transmitted persisted over a year. Similarly, children born to mothers with a history of smoking demonstrated bacteria with more virulence genes consistent with the bacteria found in smokers and, on average, 81% of these transmitted virulence genes persisted over 1 year. Lastly, maternal intra-gestational exposure was a bigger driver of the both the taxa and functional content of the babybiome than age of the child or the change in the child’s dentition across the CARD and VFDB databases (p-value = 0.041 for taxa, p-value = 0.047, 0.05 for CARD and VFDB respectively). The KEGG database did not show significant differences (p-value = 0.109). When looking at the virome, however, maternal exposures did not affect the alpha (Shannon index, p-value=0.8) and beta diversity (Aitchison index, p-value=0.7). Each infant shared a widely variable amount of the virome their cognate mothers (18-73% if mothers had been treated with antibiotics, 28-90% if the mother was healthy and 11-50% if the mother smoked). Conclusion: The baby bacteriome is derived from the maternal biome and infants exhibit a stable colonization of the oral bacteriome over 12 months, persisting through the eruption of primary teeth. Because habits and systemic influences, such as smoking, antibiotic use, and disease can create dysbiotic microbiomes, children of mothers in a state of dysbiosis may be predisposed for harm later in life. The infant oral virome, however, is only partially derived from the maternal biome. Furthermore, the virome is more heavily impacted by the age of the infant rather than maternal exposures. Further work is needed to determine which viruses comprise the majority of the virome as well as the interactions between the virome and microbiome.

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Health Sciences: 3rd Place (The Ohio State University Edward F. Hayes Advanced Research Forum)

Keywords

virome, oral microbiome, infant, bacteriome

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