Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract and so belongs to a group of conditions known as inflammatory bowel diseases. In a recent study, researchers from Massachusetts General Hospital and the Broad Institute discovered that the intestinal bacteria in newly diagnosed pediatric patients, who had not yet been given medicine for Crohn's disease, differed from that of individuals without inflammatory bowel disease. “The data presented here provide a unique framework for understanding the microbial [imbalance] in new-onset Crohn’s disease,” wrote the authors in the conclusion of their report, which appears in Cell Host and Microbe.

What is Crohn’s disease?

Although Crohn’s disease can affect any part of the gastrointestinal tract from mouth to anus, it most commonly affects the ileum, or end of the small bowel, and the beginning of the colon. Symptoms of the disease vary from patient to patient, though the most common are: persistent diarrhea, rectal bleeding, abdominal cramps and pain, constipation, urgent need to move bowels, sensation of incomplete evacuation of the bowels. More general symptoms include fever, loss of appetite, weight loss, fatigue, night sweats, and for young women, loss of a normal menstrual cycle. Because it is a chronic disease, patients with Crohn’s will likely experience symptomatic periods followed by periods of remission with no symptoms. In severe cases, the disease can lead to tears in the lining of the anus, which may cause pain and bleeding, or it may cause the development of a fistula, which would require immediate medical attention.

Men and women are equally likely to be diagnosed with the disease, and though it can occur at any age, it frequently appears among adolescents and young adults between the ages of 15 and 35. According to the Crohn’s and Colitis Foundation of America, it may affect as many as 700,000 Americans. Over the long term, up to 75 percent of patients with Crohn’s disease will require surgery. This is only necessary when medication — there are currently several options within five separate drug categories — no longer controls the symptoms.

A Study of Newly Diagnosed Children

To conduct the current research, a team of scientists analyzed data from the RISK Stratification Study, which was designed to investigate the factors involved in newly diagnosed pediatric cases of Crohn's disease or other inflammatory bowel diseases. At 28 institutions across the U.S. and Canada, intestinal tissue samples were taken from 447 children with a clear diagnosis of Crohn's and 221 control participants with non-inflammatory gastrointestinal conditions. The researchers also analyzed samples from an additional group of about 800 participants in previous studies, for a total of more than 1,500 individuals.

In particular, the researchers focused on the microbiome — the genome of the entire microbial population residing in the gastrointestinal tract. Nearly 100 trillion bacteria, known as gut microbiota or gut flora, live inside us and help break down the food we eat. These bacteria are crucial to the development of our immune systems and even produce hormones. Weighing up to 4.25 lbs., gut microbiota collectively contain 3.3 million genes a hundred times the number contained in the human genome. For the current study, then, the researchers sequenced each participant’s microbiome and compared results.

A significant decrease in diversity was found in the microbial population taken from tissue samples at the beginning and the end of the large intestine of Crohn's patients, who had not yet received treatment for their disease. The researchers identified a proportional increase in inflammatory bacteria and a decrease in non-inflammatory, beneficial bacteria in Crohn's patients when compared with participants without the disease. (Specifically, they found an increase of Enterobacteriaceae, Pasteurellaceae, Veillonellaceae, and Fusobacteriaceae, and a decrease of Erysipelotrichales, Bacteroidales, and Clostridiales).

This imbalance was even greater in patients whose symptoms were more severe. Plus, a comparison of patients who had taken antibiotics with those who had not indicated antibiotic use amplifies microbial imbalance. "Identifying which microbial products are key to disease onset and to inflammation resolution in inflammatory bowel disease and establishing which can be effectively targeted are our best hope to uncover the first microbiome-based therapies,” said senior author Dr. Ramnik Xavier, chief of the Gastrointestinal Unit at Mass General Hospital. In short, learning more about the composition of the bacteria living in our guts will lead to better therapies for those who suffer from this condition.

 

Source: Gevers D, Kugathasan S, Denson LA, et al. The Treatment-Naive Microbiome in New-Onset Crohn’s Disease. Cell Host and Microbe. 2014.