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Discovering the World Within Us

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Discovering the World Within Us
January 31, 2024

CHOP clinicians detail how they are harnessing the microbiome to promote healing in patients 

The human body is an intricate ecosystem teeming with trillions of microorganisms, collectively known as the microbiome. This complex community, comprising bacteria, fungi and viruses, resides on our skin, in our gut, and throughout our bodies, playing a pivotal role in our overall health and well-being.

At Children's Hospital of Philadelphia (CHOP), we are on a mission to unravel the mysteries of the microbiome and harness its immense potential to treat diseases and promote optimal health for children.

At the heart of these endeavors is the CHOP Microbiome Center, a state-of-the-art facility endowed with cutting-edge technologies for high-throughput sample preparation, sequencing and comprehensive data analysis.

Our center is co-directed by Robert N. Baldassano, MD, and Frederic C. Bushman, PhD, both renowned experts in their fields. Kyle Bittinger, PhD, who heads the analytical core, and Ahmed M. Moustafa, BPharm, PhD, who directs the sequencing core, contribute their extensive expertise, driving the center’s success in microbiome research and application. Together, this team has successfully spearheaded more than 435 projects, collaborated with 163+ principal investigators from 44 prestigious institutions, government bodies and industry partners.

Our research approach at the Microbiome Center is integrative and holistic, combining large-scale metagenomic DNA sequencing data with patient records, human genetic data and various omics-type data. This comprehensive methodology paints a nuanced picture of the human-microbe interaction, setting the stage for groundbreaking discoveries and innovative advancements in patient care.

Understanding the microbiome in our youngest, most vulnerable patients

Guided by the expertise of Dr. Moustafa, the “Microbiome Cartography (Micro Cart)” project for the CHOP Neonatal/Infant Intensive Care Unit (N/IICU) stands out as a prime example of innovative research aimed at improving patient care and infection control for some of our youngest and most vulnerable patients.

By employing cutting-edge techniques – such as shotgun metagenomics – the project aims to define the environmental microbiome, resistome, and virulome of the N/IICU.

At the same time, the project ensures that all pathogens captured during the surveys are cultured and sequenced through the microbial ARchive and Cryo-collection. This novel initiative – under the CHOP Microbiome Center is co-led by Dr. Moustafa, Paul J. Planet, MD, PhD, and Joseph P. Zackular, PhD – provides a holistic view of the microbial landscape.

The goal of Micro Cart is to establish the first environmental microbiome map specifically for a unit at CHOP. This will be a significant stride towards understanding pathogen transmission and can help inform targeted interventions to mitigate infection risk.

Understanding how antibiotics affect the microbiome

As another tangible example of the groundbreaking work happening at the CHOP Microbiome Center, Dr. Bittinger and his team are investigating the response of the gut microbiome to antibiotics. The team developed a bioinformatics tool – the Microbiome Response Index (MiRIx) – that uses antibiotic susceptibility data to measure the impact of a specific antibiotic on the gut microbiome.

Researchers are applying this new approach to compare antibiotic regimens in premature infants, in collaboration with Sagori Mukhopadhyay, MD, MMSc, a CHOP neonatologist at Pennsylvania Hospital.

In a separate study, researchers are using this same approach to distinguish the effects of disease and antibiotics on the gut microbiome of children with inflammatory bowel disease.

The approval of fecal microbiota by the U.S. Food and Drug Administration (FDA) marks a historic moment in microbiome research and application. This novel microbiota-based live biotherapeutic has demonstrated its efficacy in preventing the recurrence of Clostridioides difficile infection (CDI) in adults.

At CHOP, we are excited to be part of this revolutionary phase in microbiome research and application.

This article was written in collaboration with Robert N. Baldassano, MD, Frederic C. Bushman, PhD, Kyle Bittinger, PhD, and Ahmed M. Moustafa, BPharm, PhD, all of whom work with the Microbiome Center at CHOP.

Looking for help with sequencing and analytics to advance your project?  

The CHOP Microbiome Center is the sequencing and analytical resource of the PennCHOP Microbiome Program, providing end-to-end solutions for microbiome research. 

Learn how we can support you. 

 

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