Reply to "Too Soon to Dismiss Inflammation-Related Differences in the Mucosa-Associated Microbiota in Crohn's Disease Patients".

To the Editors:

We appreciate the interest as well as valuable comments from Libertucci et al concerning our work.[1]

As pointed out by Libertucci et al, we used 16s ribosomal RNA sequencing to analyze and compare the composition of bacteria in the ileal mucosa of patients with Crohn’s disease (CD) and healthy control (HC) subjects as well as to compare the inflamed and proximal noninflamed mucosa within patients with CD. As previously found in fecal and colon samples,[2] we found a clear separation in bacterial composition between CD patients and HC subjects. When comparing inflamed and noninflamed mucosa, one could anticipate a difference in bacterial composition either as a primary factor driving focal inflammation or as a secondary phenomenon owing to the impaired mucosal defense mechanisms in an inflamed or ulcerated segment of the intestine. However, whereas we found large differences between CD patients and HC subjects, such differences were not found when comparing the inflamed and noninflamed ileal mucosa within patients with CD. This finding parallels the findings in the inflamed and noninflamed colonic mucosa previously reported by the authors[3] as well as by others.[4] Although this rules out neither differences in composition at the species or strain level nor differences in what bacteria produce and how they behave, it must suggest that the changes within a patient are minor compared with the major alterations in microbiota that seem to affect larger areas of the intestinal mucosa in CD patients. Some differences found using increasingly sensitive methods could also be secondary to inflammation with ulcerations that compromise antimicrobial defense.

However, the microbiome comprehends more than bacteria, and differences in fungal or viral composition between inflamed and noninflamed mucosa could also be of importance to understand the mucosal inflammation in inflammatory bowel disease. We agree with Libertucci et al that further investigations of the mucosa-associated microbiota and between inflamed and noninflamed mucosa are of interest to understand the pathogenesis of CD.