Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation.

BACKGROUND: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. METHODS: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. FINDINGS: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. INTERPRETATION: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. FUNDING: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).

A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis.

BACKGROUND: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised. METHODS: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting. FINDINGS: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features. INTERPRETATION: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.

Effect of a microencapsulated feed additive of lactic and formic acid on the prevalence of Salmonella in pigs arriving at the abattoir.

The main objective of this work was to investigate the potential of a microencapsulated mixture of organic acids (formic and lactic acid) added to the feed of fattening pigs to reduce the prevalence and shedding of Salmonella when arriving to the abattoir. Two trials were performed. In Trial 1, 24 fattening pigs received one of three diets: a control diet, the same diet including lactic and formic acid (0.4% each) (non-protected blend; NPB), or a lipid microencapsulated blend (0.14% each acid) (protected blend; PB). After 10 days, digesta samples from various parts of gastrointestinal tract were taken. No changes were detected either in pH, total short chain fatty acids (SCFA), lactic/formic acid concentrations in any of the sections studied or in caecal lactic acid bacteria or enterobacteria. In Trial 2, 261 pigs from a commercial farm were distributed between the three previous diets in the five weeks before slaughtering. At the abattoir, no change was detected in caecal pH, but increased concentrations (p < 0.05) of formic and lactic acid were found with the NPB and PB treatments. The total SCFA concentration was higher with the PB compared to the control diet (p = 0.002) with a lower percentage of branched chain fatty acids. Both acidified diets decreased enterobacteria in the caecum but did not modify lactobacilli. NPB treatment decreased Salmonella seroprevalence (p < 0.001). A significant (p < 0.05) increase in Salmonella faecal shedding was found related to the stress previous to slaughter with the control group and PB, but not in the NPB group. More studies will be needed to confirm the usefulness of protected acids to prevent Salmonella prevalence and shedding at the abattoir.