Booth, C. | Search bioRxiv

bioRxiv2019

Bifidobacterium breve UCC2003 exopolysaccharide modulates the early life microbiota by acting as a dietary substrate

Members of the genus Bifidobacterium represent an important bacterial group for promoting health during early life. Previous studies have indicated that bifidobacterial exopolysaccharides (EPS) are involved in host interactions, with purified EPS also suggested to modulate microbe-microbe interactions by acting as a nutrient substrate. To further explore the role of EPS as a potential dietary component, we determined the longitudinal effects of bifidobacterial EPS on microbial communities and metabolite profiles using an infant model colon system. Bifidobacterium breve UCC2003 was utilised as a representative early life bifidobacterial strain, and a corresponding isogenic EPS-deletion mutant (B. breve UCC2003 EPS-). Initial transcriptomics analysis of the EPS mutant vs. parent B. breve UCC2003 strain highlighted differential expression in a discrete number of genes, including the eps biosynthetic cluster, though overall growth dynamics between the two strains were unaffected. Model colon vessels were inoculated with B. breve strains and microbiome dynamics were monitored using metataxonomic (via 16S rRNA sequencing) and metabolomic (via 1H NMR) approaches. Baseline early life microbiota profiles were similar between vessels, with persistence of B. breve (EPS+ and EPS-) observed between 0-36h. Within the EPS-positive vessel there was a significant shift in microbiome and metabolite profiles until the end of the study (405h); we observed increases of Escherichia and Tyzzerella, and short-chain fatty acids including acetate, propionate and formate, including further correlations between taxa and metabolites which were not observed in the EPS-negative vessel. These data indicate that the B. breve UCC2003 EPS is potentially being metabolised by members of the infant microbial community, leading to differential microbial metabolism and altered metabolite by-products. Overall, these findings may allow for development of EPS-specific strategies to beneficially alter the early life microbiota to promote infant health.

microbiology↗

bioRxiv2019

Differential expression of soluble receptor for advanced glycation end-products (sRAGE) in mice susceptible or resistant to chronic colitis

AimsIdentifying the factors that contribute to chronicity in inflamed colitic tissue is not trivial. However, in mouse models of colitis, we can investigate at preclinical timepoints. We sought to validate murine Trichuris muris infection as a model for identification of factors that promote development of chronic colitis.\n\nMethodsWe compared preclinical changes in mice with a resolving immune response to T. muris (resistant) versus mice that fail to expel the worms and develop chronic colitis (susceptible). Findings were then validated in healthy controls and patients with suspected or confirmed IBD.\n\nResultsThe Receptor for Advanced Glycation End Products (Rage) was highly dysregulated between resistant and susceptible mice prior to the onset of any pathological signs. Increased soluble RAGE (sRAGE) in the serum and faeces of resistant mice correlated with reduced colitis scores. Mouse model findings were validated in a preliminary clinical study: faecal sRAGE was differentially expressed in patients with active IBD compared with IBD in remission, patients with IBD excluded or healthy controls.\n\nConclusionPre-clinical changes in mouse models can identify early pathways in the development of chronic inflammation that human studies cannot. We identified the decoy receptor sRAGE as a potential mechanism for protection against chronic inflammation in colitis in mice and humans. We propose that the RAGE pathway is clinically relevant in the onset of chronic colitis, and that further study of sRAGE in IBD may provide a novel diagnostic and therapeutic target.

immunology↗