237 unclear how this protective mechanism of MUC4 deletion works, but it has been hypothesized that it may trigger the concomitant upregulation of other mucin proteins (e.g. MUC1-3) as these genes have been observed to be highly expressed in Muc4-knockout mice with DSS-induced colitis.42,43 Based on this, we speculate that the positive association between Alistipes abundance and MUC4 expression may imply a potential pathogenic role of Alistipes in the context of IBDassociated dysbiosis. However, in our data, we did not observe a significant interaction via dysbiotic status between Alistipes abundance and MUC4 expression. Mucosal Oscillibacter bacteria positively associate with OSM expression Oscillibacter-like bacteria, which include Oscillibacter and Oscillospira, are commonly detected in human gut microbial communities, although their exact physiological role is not fully understood. Previously, it was reported that Oscillibacter may be a potentially important bacterium inmediating high fat diet–induced intestinal dysfunction, which was supported by a negative association between Oscillibacter and intestinal barrier function parameters.44 Similarly, the abundance of Oscillibacter has been reported as a key bacterial group associated with colitis development in DSS-induced colitis in mice and with prenatal stress in rodents.45,46 However, a recent study linking gut microbiota profiles to sulfur metabolism in patients with CD demonstrated that Oscillibacter abundance was enriched in patients with inactive compared to active disease but diminished in patients with IBD compared to controls.47,48 Thus, similar to Bacteroides and Alistipes, the exact functional role of Oscillibacter in the context of IBD remains elusive, but it will likely depend on gut microbial dysbiosis and the intestinal (inflammatory) environment. The OSM gene encodes for the oncostatin M protein, a well-known inflammatory mediator in IBD that drives intestinal inflammation, mainly via activation of JAK-STAT and PI3K-Akt pathways.49 Besides induction of other inflammatory events, it primarily triggers the production of various cytokines, chemokines and adhesion molecules that contribute to intestinal inflammation.50 In addition, OSM is a marker for non-responsiveness to TNF-α-antagonists in patients with IBD.51 Considering these findings, the positive association between OSM expression and Oscillibacter abundance we observe supports a potentially pathogenic role for this bacterial species in IBD. Mucosal Blautia bacteria associate with host ST13 expression levels Hsc70-interacting protein, encoded by the ST13 gene, mediates the assembly of the human glucocorticoid receptor, which requires involvement of intracellular chaperone proteins such as heat shock proteins HSP70 and HSP90.52 Reduced expression of ST13 has been observed in patients with colorectal cancer, suggesting that ST13 may constitute a candidate tumorsuppressor gene.53,54 The positive association we observe between mucosal Blautia abundance and ST13 gene expression may therefore point to a protective anti-carcinogenic role for Blautia in the intestines. Mucosal host-microbe interactions in IBD
RkJQdWJsaXNoZXIy MjY0ODMw