Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.

BACKGROUND: Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. METHODS: Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. RESULTS: The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. CONCLUSIONS: A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.

Rationale for monitoring cyclosporine concentration at 2 hours after administration in infants posttransplantation.

Therapeutic drug monitoring is critical to avoid overimmunosuppression or underimmunosuppression in young pediatric transplant recipients. The objective of this study was to examine cyclosporine (CsA) trough (C0) and 2-hour post-dose (C2) concentrations in the early period after liver transplantation (OLT) to determine whether CsA C2 monitoring is justified. Seventeen infants younger than 2 years treated with CsA (Neoral) were monitored at C0. The biopsy-proved acute rejection rate was 65% at 3 months post-OLT. No correlation was observed between values at C0 and C2. Poor absorption of CsA was observed in most infants during the first 2 weeks post-OLT, as well as interindividual variability in CsA clearance. Exposure to CsA could not be estimated using either C0 or C2 determinations in the early post-OLT period. As a marker of poor absorption, C2 is useful but does not indicate delayed or rapid clearance of drug without simultaneous measurement of concentration at C0. We suggest the use of both C0 and C2 monitoring, or AUC monitoring on an individual basis during at least the first 2 weeks post-OLT.