Project description:Interventions: Open label Phase 1b proof of concept study to test for dysbiosis in small cohort of people identified as at risk for developing colorectal cancer (CRC) based on the background of conventional adenomatous polyps, and the potential of a light infection with hookworm to improve microbial richness and diversity.
All participants will receive in total 20 hookworm larvae (L3) to be applied by the study nurse as two doses of 10x L3 to the skin approximately 4 weeks apart. The L3 will be applied to a non-adherent dressing which will be placed on the forearm of the participant. The dressing will need to remain in place for the remainder of the day, and disposed of at night.
Analyses of blood and rectal mucosal immune responses, mucosal and faecal microbiomes will be undertaken pre and 12 months post hookworm infection.
The fidelity of the hookworm intervention will be monitored by participant reported incidence of a rash at the inoculation site (the first week after inoculation) and laboratory tests for the typical immune response (eosinophilia) and the presence of parasite eggs in faecal samples taken at the post-inoculation clinic visits.
Primary outcome(s): A composite primary outcome including measurements of bacterial species richness (number of observed operational taxonomic units, OTUs) and bacterial species diversity (Shannon Index) in faecal and colon biopsy specimens, determined by shotgun metagenomic sequencing[Week 52 post hookworm inoculation]
Study Design: Purpose: Prevention; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Efficacy
Project description:NMR was performed on 11 saliva samples; 5 from participants classified as having dental erosion and 6 from healthy control participants with no dental erosion to assess the differences in metabolome between the two groups. NMR analysis alone revealed no significant differences between the dental erosion and healthy controls. However, bacterial mRNA sequencing of the oral microbiome from the same saliva samples was performed and the bacterial gene expression profiles was correlated to metabolite concentrations in the groups. The dental erosion group had strong correlations between metabolites associated with protein degradation and amino acid fermentation (formate, butyrate, propionate, 5-aminopentanoate, acetate, glycine, phenylalanine, dimethyl sulfone) and increased activity of species including 4 Prevotella species, Actinomyces graevenitzii, Tannerella species, and 2 Selenomas species, to name a few. Whereas in the healthy control group, the only positive correlations between metabolite concentrations and bacterial activity was for urea and 5-aminopentanoate; urea was positively correlated with Aggregatibacter actinomycetecomytans, Lysinibacillus fusiformis, and Veillonella tobetsuensis, and 5-aminopentanoate was positively correlated with 3 different Leptotrichia species, Streptococcus parasanguinis, and 2 Prevotella species.
Project description:As a good niche for bacterial growth, appendix plays a very important role in maintaining and protecting intestinal symbiotic flora. Appendectomy will lead to intestinal microecological disorders. Therefore, we put forward the hypothesis that "appendectomy leads to intestinal microecological disorders and then increases the risk of colorectal cancer". In this study, the feces of normal controls, appendectomy and patients with colorectal cancer were collected, and the specific changes of intestinal flora after appendectomy were explored in detail from the level of family, genus and species by macrogenomic sequencing. Then through functional gene analysis, metabolic pathway analysis and other methods to explore the molecular mechanism of colorectal cancer risk changes and the changes of microflora involved, and verified by mouse fecal bacteria transplantation animal experiment.
Project description:Aliivibrio wodanis and Moritella viscosa have often been isolated together from fish with winter ulcer. Little is known about the interaction between the two bacterial species and how the presence of one bacterial species affects the behaviour of the other. The impact on bacterial growth in co-culture was investigated in vitro, and the presence of A. wodanis has a strong inhibitorial effect on M. viscosa. Further, we have sequenced the complete genomes of these two marine Gram-negative species, and have performed transcriptome analysis of the bacterial gene expression levels from in vivo samples. Using bacterial implants in the fish abdomen, we demonstrate that the presence of A. wodanis is altering the gene expression levels of M. viscosa compared to when the bacteria are implanted separately. The impeding effect on growth and the change in the global gene expression pattern of M. viscosa when the two pathogens co-exists is discussed in this paper.