NYU researchers have found a "microbial signature" of pediatric Crohn's disease that differs from the makeup of gut bacteria in children with other gastrointestinal conditions, with Crohn's patients harboring more pro-inflammatory bacteria and less protective bacteria.
The study of recently diagnosed children, published in the journal Physiological Reports , also reveals different bacteria in those with more severe Crohn's disease symptoms and activity.
Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, and rates of pediatric diagnoses have markedly grown over the last two decades. Scientists believe several factors contribute to its development, including the body's abnormal immune response, genetics, and the environment.
A growing body of research shows that the gut microbiome—the community of bacteria and other microorganisms that live in our digestive system—plays an important role in Crohn's disease. Studies have found that people living with Crohn's have less bacterial diversity in their guts and an imbalance of "bad" and "good" bacteria.
"Microbes that colonize the gastrointestinal tract provide support for digestion and other functions to keep us healthy. But when there is a disturbance, this microbiome changes, which can cause inflammation," said study senior author Deepak Saxena , professor of molecular pathobiology and director of research innovation and entrepreneurship at NYU College of Dentistry.
While studies of the gut microbiome in Crohn's disease often include those with the disease and healthy controls, NYU researchers compared young people with different types of digestive conditions to see if their microbiomes are distinct. They examined the microbiomes of 43 children with Crohn's and 139 with a group of functional gastrointestinal issues, including irritable bowel syndrome. Both groups of children were newly diagnosed and had not yet started treatment.
Using DNA sequencing to analyze fecal samples, the researchers found significant differences in microbiome composition between pediatric patients with Crohn's disease and those with disorders of gut-brain interaction. Children with Crohn's had less microbial diversity in their guts, aligning with previous studies. Moreover, the microbiomes of children with Crohn's were enriched in certain bacteria that promote inflammation in the gastrointestinal tract (Fusobacteria and Proteobacteria) and were depleted in more favorable bacteria (Firmicutes and Verrucomicrobia).
The researchers also looked at differences in the gut microbiomes of kids with Crohn's based on the severity of their disease and symptoms, measured using the Pediatric Crohn's Disease Activity Index. They found that children with more severe disease had even less microbial diversity, as well as higher levels of pro-inflammatory bacteria (Hungatella and Veillonella) and lower levels of protective bacteria (Lachnospiraceae).
The results suggest that analyzing the gut microbiome could be used alongside current tools like colonoscopy and endoscopy to diagnose and manage Crohn's disease and differentiate it from other gastrointestinal disorders.
"Our study underscores the potential of fecal microbiome profiling as an effective tool for understanding Crohn's disease pathogenesis, identifying microbial biomarkers, and predicting disease activity for treatment response. This, in turn, can help to improve personalized treatment and management strategies in pediatric Crohn's disease," said study author Ryan Zanganeh, a dental student at NYU College of Dentistry. Zanganeh, who was diagnosed with Crohn's disease at the age of 12, is interested in continuing this line of research to explore connections between the gut and oral microbiome, with the hope that oral microbial patterns could one day contribute to earlier disease diagnosis and improved monitoring.
Characterizing the specific bacterial makeup distinct to the Crohn's microbiome may also inform future treatments to rebalance bacteria in the gut.
"Microbiome-targeted treatment and management strategies may improve clinical outcomes in pediatric Crohn's disease," added Saxena. "For instance, developing therapeutic probiotics or using antimicrobial treatments against specific pathogens could help to improve an altered microbiome and reduce inflammation."
The researchers are continuing to study the microbiome in Crohn's disease and the role of different environmental factors.
"The microbiome both metabolizes chemical contaminants and is susceptible to them, and synthetic chemicals are known to disrupt immune processes that may predispose individuals to Crohn's. We will need to incorporate these multiple facets in future studies," said study senior author Leonardo Trasande , the Jim G. Hendrick, MD, Professor of Pediatrics at NYU Grossman School of Medicine.
Additional study authors include Jeremiah Levine, Adam Isbiroglu, Lauren Barazani, and Shelly Joseph of the Department of Pediatrics at NYU Grossman School of Medicine and Scott C. Thomas, Fangxi Xu, Mridula Vardhan, Samantha Hwang, Julia Kishanie Persaud, and Nirali Thakor of the Department of Molecular Pathobiology at NYU College of Dentistry. This study was funded by The Leona M. and Harry B. Helmsley Charitable Trust (grant # 1911-03329).
