Children with Crohn's Disease Have a Distinct Gut Microbiome Pattern From Onset

Crohn's disease in children is becoming more common. Diagnosis rates among pediatric patients have risen markedly over the past two decades, and the condition carries significant consequences - chronic abdominal pain, malnutrition, stunted growth, and a lifetime of management. Despite years of research, the causes remain only partly understood, involving a combination of immune dysregulation, genetic predisposition, and environmental factors.

One environmental factor under increasing scrutiny is the gut microbiome - the community of bacteria, fungi, and other microorganisms that inhabit the digestive tract. Studies in adults have consistently found that Crohn's patients carry less microbial diversity than healthy controls, with an imbalance between bacteria that promote inflammation and those that suppress it. Whether the same pattern holds in children, and specifically at the moment of first diagnosis before any treatment begins, has been less thoroughly examined.

A study from NYU College of Dentistry and NYU Grossman School of Medicine published in Physiological Reports now addresses that question - and adds a critical comparison group: children with functional gastrointestinal disorders rather than healthy controls.

Why the comparison group matters

Most microbiome studies in Crohn's disease compare patients with healthy people. That approach identifies differences between having the disease and not having it, but it doesn't isolate what's specific to Crohn's versus what's common to any gastrointestinal condition. By comparing newly diagnosed Crohn's patients with children diagnosed with disorders of gut-brain interaction - including irritable bowel syndrome - the NYU team targeted differences more likely to be specific to Crohn's inflammatory pathology.

The study enrolled 43 children newly diagnosed with Crohn's and 139 with functional gastrointestinal disorders. Neither group had yet started treatment. Using DNA sequencing of fecal samples, the researchers mapped bacterial communities across both groups.

A consistent microbial signature

Children with Crohn's disease showed significantly lower microbial diversity compared with those with functional disorders - consistent with prior research. More specifically, their gut communities were enriched in two groups associated with gastrointestinal inflammation: Fusobacteria and Proteobacteria. At the same time, they were depleted in two groups associated with gut health: Firmicutes and Verrucomicrobia.

Within the Crohn's group, the researchers examined whether microbiome composition corresponded with disease severity as measured by the Pediatric Crohn's Disease Activity Index. Children with more severe disease had even lower diversity. They also carried higher levels of Hungatella and Veillonella - bacteria with pro-inflammatory associations - and lower levels of Lachnospiraceae, a family of bacteria that produce short-chain fatty acids known to support gut lining integrity.

"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 senior author Deepak Saxena, professor of molecular pathobiology at NYU College of Dentistry.

Potential diagnostic and therapeutic implications

Current diagnosis of Crohn's disease relies on colonoscopy and endoscopy - invasive procedures that require sedation, preparation, and clinical resources. Fecal microbiome profiling is non-invasive. The results suggest that bacterial composition data could complement existing tools, potentially helping to distinguish Crohn's from functional disorders earlier and with less procedural burden on children and families.

Characterizing the specific bacterial patterns associated with Crohn's and with disease severity also points toward therapeutic targets. Interventions designed to rebalance the microbiome - therapeutic probiotics, targeted antimicrobials, dietary modifications - could in principle be directed at reducing the overrepresented pro-inflammatory species and supporting the depleted protective ones.

"Microbiome-targeted treatment and management strategies may improve clinical outcomes in pediatric Crohn's disease," said Saxena. "For instance, developing therapeutic probiotics or using antimicrobial treatments against specific pathogens could help to improve an altered microbiome and reduce inflammation."

What the study cannot determine

The study is cross-sectional and observational. It cannot establish whether the microbiome differences precede and contribute to Crohn's pathology, or whether they are a consequence of the inflammatory environment that characterizes the disease. Longitudinal studies tracking children before diagnosis - difficult logistically but possible in high-risk populations - would be needed to answer that question.

The sample size, particularly on the Crohn's side with 43 patients, limits statistical power for some comparisons. The children were all drawn from a single institution, which could affect generalizability. The researchers acknowledge these limitations and note that incorporating environmental factors - including chemical exposures and dietary patterns - will be necessary in follow-up work.

This study was funded by The Leona M. and Harry B. Helmsley Charitable Trust.