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Microbiome-based therapies for inflammatory bowel diseases offer a novel and promising therapeutic approach. The human commensal bacteria of the species Christensenella minuta (C. minuta) have been reported consistently missing in patients affected by Crohn’s disease (CD) and have been documented to induce anti-inflammatory effects in human epithelial cells, supporting their potential as a novel biotherapy. This work aimed at selecting the most promising strain of C. minuta for future development as a clinical candidate for CD therapy. Here, we describe a complete screening process combining in vitro and in vivo assays to conduct a rational selection of a live strain of C. minuta with strong immunomodulatory properties. Starting from a collection of 32 strains, a panel of in vitro screening assays was used to narrow it down to five preclinical candidates that were further screened in vivo in an acute TNBS-induced rat colitis model. The most promising candidate was validated in vivo in two mouse models of colitis. The validated clinical candidate strain, C. minuta DSM 33715, was then fully characterized. Hence, applying a rationally designed screening algorithm, a novel strain of C. minuta was successfully identified as the most promising clinical candidate for CD.

Background There is increasing evidence that microbiome-based therapies can correct dysbiosis and reduce inflammation associated with Inflammatory Bowel Diseases (IBD). In particular, the human commensal family of Christensenellaceae bacteria has been reported as missing in several cohorts of Crohn’s disease patients, indicating that it may have a role in maintaining microbial symbiosis in this population. To assess its potential for IBD management, we used the reference type species Christensenella minuta DSM 22607 to examine its anti-inflammatory properties. Methods We first performed two distinct independent preclinical colitis models: i) a moderate DNBS-induced colitis model in mice and ii) a severe TNBS-induced colitis model in rats. To decipher the mechanisms of action of C. minuta underlying the observed effects, we determined its ability to produce short chain fatty acids (SCFA) at different growth phases and we assessed its capacity to modulate the inflammatory response of human colonic cells. Results Our results showed that in both rodent models, C. minuta prevented intestinal damages by decreasing macroscopic scores, reduced colonic inflammation by limiting neutrophils infiltration in the colon and stimulated mucosal healing. We also confirmed that C. minuta is a high acetate and moderate butyrate producer. Finally, we showed that C. minuta displayed potent anti-inflammatory properties by decreasing the secretion of the pro-inflammatory cytokine IL-8 through NF-kB inhibition in HT-29 cells. Conclusion Together, these results revealed for the first time the strong anti-inflammatory properties of C. minuta and confirm its high potential as an innovative microbiome-based biotherapy for IBD.

Fumonisin B1 (FB1 ) is a mycotoxin produced by several Fusarium species and is a very common contaminant of maize-based food and feed throughout the world. The selection and use of FB1 -degrading microorganisms appears as a promising alternative to cope with the problem of toxicity towards humans and livestock. High moisture maize grain silage, which is based on natural maize fermentation, could be an interesting reservoir of such microorganisms.; Results: Using an in vitro simulated silage model with FB1 naturally contaminated grains, we demonstrated a significant raw decrease in FB1 during ensiling process ascribed to biodegradation mechanisms. A panel of 98 bacteria and yeasts were isolated from this matrix and selected for their ability to use FB1 as the sole source of C and N. For nine of them, the ability to degrade FB1 in vitro was evidenced. Notably, two bacteria identified as Lactobacillus sp. were highlighted for their efficient FB1 -degrading capacity and production of hydrolysed FB1 as intermediate degradation metabolite.; Conclusion: Fermentation of high moisture maize grain contaminated with FB1 leads to a significant reduction of the toxin and allows the isolation of FB1 -degrading microorganisms that could further be used as FB1 decontaminating agents. © 2016 Society of Chemical Industry.; © 2016 Society of Chemical Industry.

Fumonisin BUsing an in vitro simulated silage model with FBFermentation of high moisture maize grain contaminated with FB