An in silico analysis of bacteriocin production in the human microbiota and its relationship with health

Advances in computing power and metagenomic sequencing have facilitated the sourcing of a wealth of evidence to support the long-held belief that the complex community of microorganisms inhabiting the human gastrointestinal tract has significant influence on the health of the host. Equally, disruption of the composition and function of this population has been associated with many disease states. Therefore, it stands to reason that selective modulation of the gut microbiota, through antimicrobials, probiotics, or diet, presents an attractive therapeutic approach to the treatment of these diseases. One category of antimicrobials with this potential is the bacteriocins – antimicrobial peptides produced by many lineages of bacteria that kill or inhibit the growth of specific competitors. This thesis focuses primarily on the first step toward harnessing the bacteriocin-producing capacity of the human microbiota to bring about desired changes, i.e., identification of potential bacteriocin-producing bacteria using in silico genomic and metagenomic screening approaches. It highlights numerous putative bacteriocin-producing bacteria, including many from genera either not previously associated with bacteriocin-production or recently under consideration as the next generation of probiotics. It also investigates the relationship between diet, the gut microbiota, and bacteriocin gene cluster density in elite athletes and healthy controls, in addition to evaluating the effect of probiotic supplementation of the gut microbiota and overall health in a diet-induced obesity mouse model. Taken together these results show that there is a vast reservoir of putative bacteriocin-producing bacteria in the human microbiota with the potential to impact human health in a beneficial manner and highlights diet as a major factor in influencing the density and distribution of these putative producers.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2017

Author dc:creator

• Walsh, Calum J.

Advisors dc:contributor.advisor

• Cotter, Paul D.
• O'Toole, Paul W.
• Ross, R. Paul

• Bioinformatics
• Microbiota
• Bacteriocin

Statement dc:rights

• © 2017, Calum Walsh.

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/3.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/4708

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/4708