IBD, Crohn's disease, and the microbiome

There have been several large scale studies that show a definite association between the microbiome and inflammatory bowel diseases like Crohn’s and colitis.  While it is becoming clear that the microbiome plays a pivotal role in these diseases, the exact mechanisms of pathogenesis are not known.  One of the reasons it has been so hard to uncover this link is because of a lack of robust studies, that usually contain small sample sizes.  In response, a team of leading scientists in the field, including multiple scientists from our own scientific advisory board, assembled a brand new cohort, the largest of its kind, to study the disease.  The cohort consisted of 447 children with newly diagnosed, still untreated, Crohn’s disease and 221 healthy children.   They then combined this data with two other cohorts that included adult patients to bring the total number of samples to 1,742.  The first results of this study were published in Cell Host and Microbe, and shed many insights into IBD and its relationship to the microbiome.

In the study the researchers sampled and sequenced the microbiome of the gut mucosa and stool.  From this data, they identified specific bacteria that had higher abundances in diseased patients, like Enterobacteriaceae and Veillonellaceae, and others that had lower than normal abundances, such as Clostridiales and Bacteroidales.  According to the samples, these relative abundances were more pronounced in the mucosal samples, rather than the stool samples, meaning that the mucosa may play a more important role in Crohn’s pathogenesis and diagnosis.  Moreover, children under age 10 did not have large populations of the ‘bad’ bacteria, which were negatively correlated with age.

Another important finding from the study is that antibiotic treatment of the Chrohn’s disease further exacerbated the microbial imbalances (dysbiosis), and caused the bad bacteria to proliferate and the good bacteria to die off.  The researchers are quick to dismiss antibiotics as the cause of the disease, rather hypothesizing that the antibiotics allow for opportunistic bacteria to grow which may cause dysbiosis.  They also encourage further research on the subject and question whether antibiotics should be prescribed to IBD patients.

The researchers used this knowledge of the dysbiosis to create a potential diagnostic for IBD.  They were able to calculate a microbiome diversity index by sampling the mucous for the existence of certain bacteria and for overall microbiome diversity.  The index shows remarkable ability to not only accurately predict the existence of IBD, but also the severity of it.  Also, the researchers showed their microbiome dysbiosis index could be combined with clinical data to better predict the future outcome of the disease.

A final conclusion of the paper is that the gut mucous is a more accurate signal for IBD.  They conclude that stool samples are composed of higher levels of aerobic, oxygen using, bacteria than those in gut, and that stool is not representative of the overall microbiome.

This study is the first to rigorously tackle IBD, specifically, Crohn's disease, and the microbiome.  We now know what bacteria are most highly associated (both positively and negatively) with IBDs, and how this this information can be incorporated into early diagnostic screens.

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