Mucosa‐attached bacterial community in Crohn's disease coheres with the clinical disease activity index

Abstract

In inflammatory bowel diseases (IBD), microbial communities often become imbalanced suggesting abnormal microbial-gut interactions. In this study, we analysed the mucosa-attached gut microbiota from 26 Crohn's disease (CD) patients using 16S rRNA gene amplicon sequencing. The samples were stratified according to their disease activity (Crohn's disease activity index, CDAI). The different disease activity categories had a comparable bacterial richness. Bacterial communities of patients in remission and intermediate CDAI (0-220) were relatively similar and dominated by the genus Bacteroides (>40%). The bacterial composition of patients assigned to a high CDAI category was dominated by Pelomonas (25%) and Flavobacterium (13%) but had a low relative abundance of Bacteroidetes (4%). This indicates the presence of specific abundant bacterial taxa at different CDAI levels. In addition, bacterial communities were also significantly influenced when a tumour necrosis factor (TNF)-α inhibitor was applied or by the local mucosal inflammation level. As a consequence, a shift of the microbial composition may also indicate a change of the disease activity in CD patients.

Influence of diet on the gut microbiome and implications for human health

“…The exact mechanism of how these gut flora modulate immune responses is still not well understood; however, several studies suggest that microbial-derived SCFAs may be contributing via G-protein-coupled receptor and epigenetic mechanisms [141, 142]. Intestinal SCFAs have also been shown to directly increase the abundance of T regulatory cells in the gut and to protect against allergic airway inflammation [17, 143–145]. In addition, they may inhibit the transcription factor NF-κB, leading to decreased secretion of several pro-inflammatory cytokines [130].…”

“…Butyrate and other SCFAs are thought to have a direct anti-inflammatory effect in the gut [16]. Furthermore, different indices of Crohn’s disease activity have each been characterized by specific gut mucosa-attached bacteria, that in turn are significantly influenced by anti-TNF therapy [17]. The relative abundance of different bacteria may mediate intestinal inflammation and Crohn’s disease activity through effects on local regulatory T cell populations [17, 18].…”

“…Furthermore, different indices of Crohn’s disease activity have each been characterized by specific gut mucosa-attached bacteria, that in turn are significantly influenced by anti-TNF therapy [17]. The relative abundance of different bacteria may mediate intestinal inflammation and Crohn’s disease activity through effects on local regulatory T cell populations [17, 18]. Furthermore, overrepresentation analysis has shown that enzymes enriched in IBD microbiomes are more frequently involved in membrane transport, which could support a “leaky gut hypothesis” contributing to the disease state [19, 20].…”

Vitamin D administration leads to a shift of the intestinal bacterial composition in Crohn's disease patients, but not in healthy controls

“…The isolated DNA was amplified with the bacterial 16S ribosomal RNA (rRNA) gene primers Bakt_341F (CCTACGGGNGGCWGCAG) and Bakt_805R (GACTACHVGGGTATCTAATCC) . The amplicon PCR, the index PCR, a quantity and a quality control and the sequencing of the individual libraries as a pool in one Illumina MiSeq run was performed as described in a previous study . The raw sequences of the study were deposited at the Short Sequence Archive (SRA) under the accession number ‘PRJEB21819’.…”

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

“…Active IBD and experimental ileocolitis directly alters bacterial composition and gene expression 44, 78–81 , luminal (fecal) and mucosal dysbiosis in various intestinal regions correlates with disease activity, being less abnormal in unaffected regions 69, 70, 79 . Proposed mechanisms for inflammation-induced reduction of strict anaerobes, such as Clostridium groups IV or XIVA, with parallel expansion of aerobic and facultative anaerobic taxa belonging to the Proteobacteria phylum such as Enterobacteriacea, include increased ambient oxygen concentrations with hyperemia and increased vascular and mucosal permeability 82 disruption of physiologic epithelial NA+/H+ exchange causing dysregulated electrolyte concentrations 80 , and the production of alternative electron acceptors that promote anaerobic respiration of facultative anerobes 83 .…”