Skip to main content
Premium Trial:

Request an Annual Quote

Study Outlines Gut Microbial Shifts Seen in New Childhood Crohn's Disease Cases

NEW YORK (GenomeWeb News) – A new study is spelling out some of the distinct gut microbiome features found in individuals diagnosed with Crohn's disease who have not yet received treatment for the condition.

A team from the Massachusetts General Hospital, the Broad Institute, and elsewhere used 16S ribosomal RNA gene sequencing to compare microbial community membership in gut microbiomes from almost 450 children with Crohn's disease with those found in more than 200 control individuals with gastrointestinal problems not associated with inflammatory bowel disease.

As they reported online today in Cell Host & Microbe, the researchers saw diminished microbial diversity, coupled with an over-representation of microbes implicated in inflammatory processes, in the Crohn's disease gut microbiomes — findings that they confirmed by resequencing previously collected samples from hundreds more children or adults with Crohn's disease or other forms of inflammatory bowel disease.

Such microbiome shifts were even more pronounced in children with severe Crohn's symptoms, suggesting there may be a therapeutic benefit to restoring more diverse and less inflammation-prone gut microbiomes.

"These results identifying the association of specific bacterial groups with Crohn's disease provide opportunities to mine the Crohn's-disease-associated microbiome to develop diagnostics and therapeutic leads," the study's corresponding author Ramnik Xavier, director of the Massachusetts General Hospital's Center for the Study of Inflammatory Bowel Disease and gastrointestinal chief at MGH, said in a statement.

Past studies suggest an individual's genetics can contribute to his or her risk of Crohn's disease and other forms of inflammatory bowel disease, in part by mediating immune responses to microbes in the gut.

A growing body of evidence has also uncovered changes in gut microbial community composition in those with IBD, authors of the new study noted, though the precise nature of alterations detected in the gut microbiomes of affected individuals seems to vary somewhat from one study to the next.

As part of a project called the RISK Stratification Study, Xavier and his colleagues used 16S rRNA gene sequencing to assess pre-treatment intestinal tissue and/or stool samples from 447 children with clear cut Crohn's cases who had been diagnosed at one of 28 centers in the US or Canada. They also tested samples from 221 control individuals with non-inflammatory forms of gastrointestinal disease.

Using Illumina's MiSeq instrument, the team did 16S sequencing on 1,321 samples collected from those cases and controls, including more than 300 stool samples, 630 tissue samples taken from the ileal portion of the intestine, and nearly 400 rectal tissue samples.

When they compare gut microbiome profiles generated using DNA from tissue samples taken from children with or without Crohn's disease, the researchers found that the gut communities in Crohn's patients typically showed a dip in species diversity, particularly among microbes from Enterobacteriaceae, Bacteroidales, and Clostridiales families.

On the other hand, the individuals suffering from intestinal inflammation tended to carry gut microbial communities with higher-than-usual levels of bugs belonging to families such as Pasteurellaceae, Veillonellaceae, Neisseriaceae, and Fusobacteriaceae.

Such patterns were even more pronounced in the subset of Crohn's patients exposed to antibiotics prior to sample collection, the researchers reported, noting that the findings "do not provide a causative explanation but are relevant in the context of previously described associations between higher antibiotic exposure and the diagnosis of [Crohn's disease]."

Particularly high levels of the Pasteurellaceae and Veillonellaceae microbes also tended to coincide with the presence of deep intestinal ulcers in Crohn's patients, as did the presence of pathogenic forms of Escherichia coli.

Even so, additional research is required to understand whether any of the detected associations are causative, the study's authors noted, or whether such bugs are simply well suited to the gut environment created when ulcers occur.

Because the proportion of host DNA is very high in ileal and rectal tissues, the team did not attempt metagenomic sequencing on those samples. Instead, it used 16S sequence data and a predictive algorithm to get a sense of the functional capabilities of microbes in the gut samples. That analysis pointed to a rise in organisms associated with oxidative stress, aerobic respiration, and benzoate metabolism in Crohn's disease-associated communities, for instance.

The gut microbiome shifts were less obvious when the group used the Illumina HiSeq 2000 to do metagenomic sequencing on stool samples from a few dozen of the newly diagnosed Crohn's cases and 10 controls, though some of the same general shifts in microbe function could be detected.

Moreover, the researchers noted that "by adding metagenomics data on the subset of stool samples, we were able to profile the composition of microbial communities at a finer taxonomic resolution."

With the help of samples taken six months and a year after participants' Crohn's diagnoses, the team was also able to start putting together a potential microbiome-based predictive model for the development and progression of the disease.

Finally, by resequencing and comparing data from hundreds more adults and children with Crohn's, ulcerative colitis, or non-inflammatory gastrointestinal disease, the researchers saw gut microbiome patterns that appeared to reflect inherent differences between individuals, the condition involved, samples considered, disease severity, and so on.