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We recently reported in your journal the discovery of an anti-inflammatory protein produced by Faecalibacterium prausnitzii, a commensal bacterium involved in Crohn's disease (CD) dysbiosis.1 We wish to highlight and complete these recent data.
The involvement of the intestinal microbiota in the pathogenesis of CD is well recognised. It has been shown that dysbiosis (an imbalance in the composition of the intestinal microbiota) could participate in chronic and inappropriate activation of the intestinal immune system and lead to inflammation. Dysbiosis is characterised by a deficiency of certain bacteria, such as Faecalibacterium prausnitzii, which belongs to the Clostridium leptum group.2 A consortium led by Pr Philippe Seksik has shown that loss of F. prausnitzii from the intestinal microbiota is associated with development of IBD, suggesting an anti-inflammatory role for this bacterium. This assessment was subsequently verified in cellular and animal models.3
Our recent work, published in Gut, has enabled us to highlight that part of the immunomodulatory activity of F. prausnitzii is carried out by the 15 kDa protein, MAM. Intestinal epithelial cells, transfected with MAM and stimulated with various pro-inflammatory molecules, showed a significant decrease in nuclear factor (NF)-κB pathway activation compared with control cells. In vivo, mice with dinitrobenzene sulfonic acid-induced colitis receiving MAM cDNA delivered by bacterial strain Lactococcus lactis showed an improved inflammatory pattern of disease compared with those receiving the empty bacterial equivalent.1
In situ expression of MAM protein in this model of colitis shows that MAM has anti-inflammatory properties. Additionally, these in vivo data confirm the results observed in vitro on the NF-κB pathway. Until now, however, we have been unable to show the presence of MAM protein in the human intestinal ecosystem. Thus, presenting the problem: how can we link the observed biological activity in vitro with what actually happens in the gut? A proteomic study published recently provided a new angle of attack to address this outstanding issue. After having reanalysed proteomic data, obtained by colleague Professor Bart Devreese, which detailed the presence of many bacterial proteins in stool samples, we were able to identify MAM protein among several proteins from F. prausnitzii.4
This discovery is highly relevant to our work recently published in Gut and confirms that MAM protein is indeed produced by the bacterium F. prausnitzii in vivo in the gut. This represents a first step towards the elucidation of the mechanism of action of MAM protein in the intestinal ecosystem, for example, the role of the protein for the bacteria, secretion mode and mechanism of entry into eukaryotic cells.
Footnotes
Contributors EQ, PS and BD wrote the letter. M-AM and HS gave scientific advice.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.