By Dr Dragos Ciocan
CCA Hepato-gastroenterology and nutrition department Antoine-Béclère Hospital, Clamart, France
About this article
Despite the Covid-19 pandemic, this year we were able to benefit from an on-line version of the Journees francophones d’hépato-gastroenterologie (French-speaking hepato-gastroenterology congress) with the advantage of being able to access presentations recorded between 3 and 20 July 2020. These eJFHOD reached a total of 7,924 users, and 172,937 pages were viewed. As each year, original studies on the intestinal microbiota (IM) were presented at this congress.
Microbiota and colorectal cancer
Third most frequent cancer in humans, sporadic colorectal cancer (CRC) develops following interactions between the host and its environment, and the IM is thought to be implicated . Professor Sobhani presented the results of a study which investigated the links between epigenetic mechanisms promoted by bacteria of the IM and the onset of CRC . Mice transplanted with faecal samples from patients with CRC developed precancerous colonic lesions, associated with an increase in hypermethylated genes. Donors with CRC exhibited methylation anomalies of several gene promoters associated with intestinal dysbiosis. Using the identified microbial and epigenetic signatures, a pilot study (n = 266) was conducted in humans in order to develop a blood test for the diagnosis of CRC. A cumulative methylation index (CMI, measuring the hypermethylation level of 3 genes) was identified as a predictive factor in the onset of CRC. These results were validated in a prospective cohort of 1,000 patients. Intestinal dysbiosis in patients with a positive CMI was characterised by an increase in pro-methylating bacterial species. This work indicates that intestinal dysbiosis associated with CRC could promote colon carcinogenesis via deregulation of the methylation of certain genes. The cumulative hypermethylation index (CMI) and/or pro-methylating bacteria are thus potential biomarkers for CRC diagnosis, or be used in the evaluation of the effects of treatments modulating the IM in patients with CRC.
A new dysbiosis marker in Crohn’s disease
In a study coordinated by Professor Seksik, the authors studied the role of MAM (microbial anti-inflammatory molecule, produced by Faecalibacterium prausnitzii and reduced in patients with Crohn’s disease, CD ) as a biomarker of intestinal dysbiosis and diagnostic aid in CD. The authors showed that loss of MAM is associated with the diagnosis of CD. This preliminary study in a small number of patients (24 patients in relapse, 24 in remission and 12 healthy controls) paves the way to the diagnosis of CD based on the IM, but these preliminary results require validation in independent cohorts.
A new therapeutic perspective in IBD
It is known that bacteria detect and respond to environmental signals (an ability called Quorum Sensing). Of the molecules which are part of this system, 3-oxo-C12:2 is low in patients with chronic inflammatory bowel disease (IBD), this reduction appears to be correlated with the observed intestinal dysbiosis . In a study presented by D. Aguanno, the authors studied the impact of this molecule on the epithelial cells of the intestine and showed that this did not modify paracellular permeability but attenuated the deleterious effects on the tight junctions induced by pro-inflammatory cytokines. In a second study, Coquant et al. showed that 3-oxo-C12:2 exerted an anti-inflammatory effect on immunoreactive cells, partly mediated by the T2R138 receptor. This molecule may therefore have protective effects on the intestinal barrier, modulate the inflammatory response and thus represent a novel therapeutic perspective in IBD.
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3 Quévrain E, Maubert MA, Michon C, et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut 2016 ; 65 : 415-25.
4 Landman C, Grill J, Mallet J, et al. Inter-kingdom effect on epithelial cells of the N-Acyl homoserine lactone 3-oxo-C12:2, a major quorum-sensing molecule from gut microbiota. PLoS One 2018 ; 13 : e0202587.