ABSTRACT
Inflammatory bowel disease (IBD) is due to an aberrant immune response toward luminal antigens, probably commensal bacteria, in genetically susceptible subjects and is also influenced by environmental factors. An imbalanced intestinal microbiota known as "dysbiosis," characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms, has been repeatedly observed in IBD and is now recognized as a key factor in the gut inflammatory process. Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option in IBD. The goal of FMT in IBD is not only to correct the dysbiosis, but also to restore a normal dialog between the host immune system and the microbiota. Data are still scarce, but the results of the first studies suggest that FMT could be a promising therapy in IBD. More studies are needed to define the best indications, optimal timing, frequency, mode of delivery, and the optimal donor for each patient.
Subject(s)
Fecal Microbiota Transplantation , Inflammatory Bowel Diseases/therapy , Animals , Colitis, Ulcerative/etiology , Colitis, Ulcerative/therapy , Crohn Disease/etiology , Crohn Disease/therapy , Fecal Microbiota Transplantation/adverse effects , Fecal Microbiota Transplantation/methods , Feces/microbiology , Humans , Inflammatory Bowel Diseases/etiology , Microbiota , Time Factors , Tissue Donors , Treatment OutcomeABSTRACT
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 15â 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 15â 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.
Subject(s)
Bacterial Proteins/metabolism , Clostridiales/metabolism , Crohn Disease/microbiology , Dysbiosis/microbiology , Intestinal Mucosa/microbiology , Amino Acid Sequence , Animals , Anti-Inflammatory Agents/therapeutic use , Bacterial Proteins/chemistry , Bacterial Proteins/isolation & purification , Bacterial Proteins/therapeutic use , Biomarkers/metabolism , Cell Line , Colitis/chemically induced , Colitis/metabolism , Colitis/prevention & control , Crohn Disease/metabolism , Crohn Disease/pathology , Dysbiosis/metabolism , Dysbiosis/pathology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mice , Mice, Inbred BALB C , Molecular Sequence Data , NF-kappa B/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
BACKGROUND: Nutritional therapy has an established role as induction therapy in paediatric Crohn's disease. However, compliance is the main difficulty and may be greatly influenced by the administration route. AIM: To analyse the efficiency of exclusive nutrition to induce remission in children with Crohn's disease comparing fractionated oral vs. continuous enteral feeding. METHODS: The medical records of 106 patients treated by exclusive nutritional therapy [Modulen IBD (R)] by either oral or continuous enteral route were reviewed retrospectively. Comparative analyses of remission rates, changes in anthropometry, Paediatric Crohn's disease Activity Index (PCDAI), laboratory indices and compliance rates were performed. RESULTS: On exclusive enteral nutrition, at 8 weeks, 34/45 patients achieved remission in the oral group (75% on intention-to-treat analysis) and 52/61 (85%) in the enteral nutrition group (P = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (P < 0.0001) and significant improvements in anthropometric measures and inflammatory indices. No difference was observed whether Modulen IBD was administered orally or by continuous enteral feeding, apart from weight gain, which was greater in the enteral group (P = 0.041). In a subgroup of patients, mucosal healing was evidenced on follow-up endoscopies showing a clear correlation to remission. Compliance rates (87% and 90%) were similar. Nevertheless, noncompliant patients had lower mucosal healing and remission rates. CONCLUSIONS: These retrospective data suggest that the use of fractionated oral nutritional therapy might be as efficacious as continuous enteral administration to induce remission and mucosal healing in children with Crohn's disease. However, appropriate prospective clinical trials are needed to confirm these findings.
