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Research: Next generation sequencing demonstrates differences of infant feeding methods

Team analyzed breast-fed and formula-fed infant gut microbiomes.

After analyzing fecal samples from breast-fed and formula-fed infants, Delaware Clinical and Translational Research (DE-CTR) ACCEL Program investigators demonstrated differences in the bacterial genes found among the two groups.

The paper, “Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome,” was published in the Cellular and Infection Microbiology section of Frontiers in March.

The research team and paper’s authors included:

  • Matthew D. Di Guglielmo, MD, Nemours Children’s Hospital, Delaware, Chief of General Academic Pediatrics and Clinical Associate Professor of Pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University;
  • Karl R. Franke, PhD, Nemours Children’s Health Pediatric Genomics Laboratory Bioinformatician;
  • Alan Robbins, MSc, Nemours Children’s Health Pediatric Genomics Laboratory Research Lab Manager (retired); and,
  • Erin L. Crowgey, PhD, former Nemours Children’s Health Pediatric Genomics Laboratory Director of Medical Bioinformatics, and former DE-CTR ACCEL Program Management Information Systems Director.

“We were first just trying to see if there were key differences between [breast-fed and formula-fed infants] and then we will use that to make hypotheses about what might actually change the developing status or the overall health status of the infant gut in its early period,” Di Guglielmo, the Principal Investigator on the project, said.

“To better understand the importance of both taxonomy and differential gene abundance, the present study employs whole-genome fecal metagenomic next-generation sequencing and a computational pipeline previously used in our laboratory (Di Guglielmo et al., 2019). The goal of this manuscript is to expand the prior analysis in size and interpretation of the metagenomics data and create a refined and more accurate picture of the metataxonomic profile of the cohorts studied.” (Di Guglielmo MD, Franke KR, Robbins A, Crowgey EL. Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome. Front Cell Infect Microbiol. 2022;12:816601. Published 2022 Mar 4. doi:10.3389/fcimb.2022.816601)

Di Guglielmo MD, Franke K, Cox C, Crowgey EL. Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort. Hum Microb J. 2019;12:100057. doi:10.1016/j.humic.2019.100057

While the current data does not prove that one feeding method improves gut health more than the other, the researchers used next generation sequencing to demonstrate there are some differences among infants’ guts based on how they are fed.

Di Guglielmo explained that “the next generation sequencing and the more comprehensive analysis method of the wet-lab and the bioinformatics computational pipeline, allows us to talk about genes that these bacteria have less or more of,” and how those bacteria are related to gut health, including antibiotic resistance or defense against other infections and viruses.

“The goal is to, at some point, make a comment about gut health and the development of a healthy gut,” Di Guglielmo said. Di Guglielmo and the investigative team are analyzing additional data on the same patients at different ages, which will help inform gut health and the development of a healthy gut.

“We hope to put together a third manuscript that’s going to look at both how do some of these individual samples look 6 months later, a year later, 18 months later – do we see the same kind of differences in patterns between the groups?”

As part of that analysis, the team has expanded the data collection to include metabolic data from the samples. The metabolic by-product being collected, Di Guglielmo explained, is a proxy for metabolic activity, which can inform what a person’s bacterial metabolism is doing.

“For example, if we see in the breast-fed kids that there’s a high amount of short chain fatty acid A, but in the formula-fed kids it’s very low – that’s a difference. Why might that difference be? It’s probably because of the type of bacteria that are there. Does that have any bearing on health? Have other people looked at short-chain fatty acid A, for example, and shown that when you have an abundance of that in your gut you have more health issues, or you have a healthier gut? Depending on the particular fatty acid, yes.”

The research for the paper was funded in part through the ACCEL Program’s Shovel-Ready Pilot Grant Program (ShoRe PGP), which aids Principal Investigators in collecting additional data to strengthen their research grant application resubmission and address reviewers’ concerns. In addition, the DE-CTR ACCEL Program’s Biostatistics, Epidemiology, and Research Design (BERD) Core in conjunction with the Nemours Biomedical Research Informatics Center (BRIC) aided in the research.

“ACCEL has been great for me and my colleagues,” Di Guglielmo said. “All the pilot and early investigator funding is very, very helpful in getting academic productivity moving forward – I’m thankful for that.”