Exploring the Bioactive Landscape of the Gut Microbiota to Identify Metabolites Underpinning Human Health

Cuív, Páraic Ó; Burman, Sriti; Pottenger, Sian; Morrison, Mark

doi:10.1007/978-3-319-46326-1_3

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“…My results in Chapter 2 include the taxonomic assignment and phylogenetic assessment of my isolates using 16S rRNA gene sequencing; and the culture collectio n I generated includes strains affiliated with Enterococcus, Clostridium cluster IV, XIVa and XVIII, with many of these isolates appearing divergent to their nearest cultured relatives, as new "branches" in these phylogenetic trees. As such, I consider that these "new" genetically competent GIT bacteria provide us with opportunities to use techniques in bacterial genetics to assess their functional and/or ecological relevance in relation to human health and disease; which has been described in detail by Ó Cuív et al (2016). For instance, forward genetics techniques including transposon mutagenes is could be used to identify genes underpinning immunomodulatory capacities.…”

Section: Chapter 5 General Discussionmentioning

confidence: 99%

Genetic and biochemical analysis of host-microbe interactions affecting gut homeostasis: functional and genomic analysis of polyphenol catabolism by bacteria from Clostridium cluster IV

Pottenger¹

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Metagenomics offers opportunities to advance our understanding of the complexities of the microbia l communities that inhabit the human gastrointestinal tract (GIT). Whilst this research field has great potential, there are limitations and caveats that affect its impact, and the translation of the "microbiome into medicine". In particular, the number of representative microbes that still remain uncultured is substantial and constrains our capacity to define the functional roles such microbes play in health and disease. New techniques to gain representative isolates of these microbes are required, and it would also be advantageous if these microbes are amenable to genetic manipulatio n.Techniques in bacterial genetics applied to a broader diversity of human GIT bacteria would allow us to fully assess the functional aspects of their potential interactions with a host, which would expand understanding of their relation to host health and well-being. With this in mind, the aims of my PhD project were to utilize a new approach developed in our lab referred to as metaparental mating, to expand our collection of genetically tractable bacteria considered relevant to GIT homeostasis, and then assess their immunomodulatory capacity. Based on these results and findings, I then chose to undertake a more detailed and integrated culture-based and genomic analysis of two "new" bacterial isolates assigned to poorly populated and relatively uncharacterised lineages within Clostridium Cluster IV: the genera Flavonifractor and Pseudoflavonifractor.Chapter 1 provides an overview of the current literature with a focus on the roles of the GIT microbiota and its roles in host health and well-being. I provide evidence and rationale for the basis of the research undertaken throughout my PhD studies based on the gaps in our knowledge of the roles specific members of the microbiota play in the GIT of humans Specific focuses are highlighted with regards to the increasing interest in Polyphenols and their beneficial impacts on the microbiota and the host.Chapter 2 describes my use of the metaparental mating technique to recover representative isolates of Firmicutes-affiliated bacteria. I validated the utility of the metaparental mating technique to recover a broad diversity of the bacteria present in human stool assigned to these lineages, and in particular the use of a plasmid that contains the evoglow-C-Bs2 bioluminescence reporter gene, which augmented antibiotic resistance selection and the identification of transconjugant strains. My phylogenetic assessment of the isolates I recovered shows the collection includes bacteria assigned to Enterococcus, Clostridium clusters IV, XIVa and XVIII. I then assessed 22 of my recovered isolates for their ability to inhibit lipopolysaccharide-stimulated NF-κB activation of the lucifer ase reporter gene using the RAW 264.7 mouse macrophage cell line. I was able to show that 7/22 of these iii isolates inhibit NF-κB activation of the reporter gene to a magnitude similar or greater than Faecalibacterium ...

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Section: Chapter 5 General Discussionmentioning

confidence: 99%

Genetic and biochemical analysis of host-microbe interactions affecting gut homeostasis: functional and genomic analysis of polyphenol catabolism by bacteria from Clostridium cluster IV

Pottenger¹

Self Cite

View full text Add to dashboard Cite

show abstract

Exploring the Bioactive Landscape of the Gut Microbiota to Identify Metabolites Underpinning Human Health

Cited by 1 publication

References 240 publications

Genetic and biochemical analysis of host-microbe interactions affecting gut homeostasis: functional and genomic analysis of polyphenol catabolism by bacteria from Clostridium cluster IV

Genetic and biochemical analysis of host-microbe interactions affecting gut homeostasis: functional and genomic analysis of polyphenol catabolism by bacteria from Clostridium cluster IV

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