Strain Tracking to Identify Individualized Patterns of Microbial Strain Stability in the Developing Infant Gut Ecosystem

Abstract

Stable microbe and host interactions are established during the development of the infant gut microbial community that provide essential functions for the efficient digestion of food, immune development, and resistance to colonization with pathogens. To further delineate the stability of the gut microbial community during this time, we have used microbial strain tracking analysis with published longitudinal metagenomic data sets to identify strains that persist in the developing infant gut ecosystem. In the first study, 17 infants were evaluated that had not received antibiotics for 3 years after birth. An infant specific pattern was seen for stable and unstable microbial strains during this time, with only one infant having no stable strains identified out of available strains during the first 3 years. Strain tracking was also applied to follow microbes in a separate set of 14 infants that had multiple doses of antibiotics over the 3 years. In 10 out of 14 infants given multiple antibiotics during the first 3 years, we identified a unique pattern of transient strains that appeared after multiple antibiotic treatments for a short time compared to that in infants not on antibiotics. In a second, independent study, we selected a subset of 9 infants from a previously published study consisting of high-density longitudinal fecal sampling to analyze the gut microbial strain stability of Bacteroides vulgatus and Bifidobacterium adolescentis for up to 6 years following birth. Individual specific patterns were found consisting of varying dominant microbial strains that were independent of antibiotic exposure and birth mode. Our analysis demonstrates an individual specific inherent variability of extinction and persistence of microbial strains in the infant gut community during a time of development that is critical for interactions necessary for establishing normal metabolism and the development of the host immune response.

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

“…We have shown that preterm newborns are also significantly colonized by fungi during this period. 29 Future work could use this higher resolution to perform strain tracking analyses 30 or real-time reverse transcription-PCR analyses, which could provide more specific information about the assembly of the newborn microbiome. Further exploration of initial intestinal colonization is likely a fertile testbed for the ecological theory of colonization of new environments and may have a significant impact on health.…”

Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains

“…Our WSS strain-tracking analysis was conducted for all donor-recipient pairs and the full details of the WSS methods can be found in our previously published papers [8,[22][23][24][25][26]. We have additionally performed strain-tracking analysis for Bacteroides uniformis for two selected donor-recipient pairs (donor: 18-0014, recipient: 19-0024 and donor: 18-0002, recipient: 18-0018) and for Bacteroides vulgatus for three selected donor-recipient pairs (donor: 18-0014, recipient: 19-0024, donor: 18-0002, recipient: 18-0018, and donor: 18-0005, recipient: 18-0007) using StrainPhlAn with default parameters and with the options '-relaxed_parameter3, -marker_in_clade 0.1' [10].…”

Infants’ gut microbiome data: A Bayesian Marginal Zero-inflated Negative Binomial regression model for multivariate analyses of count data

“…The advent of high throughput sequencing in parallel with substantial advances in computational, molecular, and quantitative fields has opened new avenues in our understanding of trillions of microbes that call the human intestine home (termed as "human gut microbiome") [1] , [2] , [3] , [4] . In vitro and in vivo studies have shown that the human gut microbiome takes shape shortly after birth mainly via transmission from the maternal microbial pool (vagina, gut, skin, or breastmilk) and continues to develop until it becomes mature two to three years after the initial colonization [5] , [6] , [7] , [8] . Any changes that could disrupt the stability of the healthy gut microbiome, particularly at the early stages of life, could result in severe dysbiosis, which could pave the path for major health issues in adulthood [9] , [10] , [11] .…”