Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Microbiology and Immunology

Supervisor

Gregor Reid

Abstract

Using a combination of hypothesis and discovery based approaches, the goal of this thesis was to better describe novel probiotic functions and their mechanisms while striving to better understand the effect of formulation on Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei and L. rhamnosus.

Using RNA-Seq, a bacterial metatranscriptome analysis of a commonly consumed probiotic yogurt showed that the organisms adapted to storage time and flavor additions. This led to the discovery that in addition to the probiotic health benefits, members of the L. casei group (L. rhamnosus and L. paracasei) produce volatile sulfur compounds mediated by a novel sulfur/taurine metabolism gene cluster that affect taste and texture. The benefits of selected probiotic strains were tested in a further series of human studies.

A systems biology approach was developed and a double-blind, placebo-controlled clinical trial of post-menopausal women showed that vaginally administered probiotics could influence the microbiota and host responses. Changes in the vaginal microbiota were noted in late pregnancy in a rural Tanzanian population, and maternal intake of Moringa supplemented L. rhamnosus GR-1 yogurt appeared to improve the gut microbiota profile of the newborn babies. Having discovered that L. rhamnosus GR-1, and selected other lactobacilli, could sequester heavy metals in vitro, a randomized open-label pilot study was performed and showed a reduction in toxic metal uptake in Tanzanian pregnant women and school children. The latter series of findings led to the discovery, development and characterization of a new strain, L. rhamnosus Lr60, with high potential to reduce toxic metal accumulation in the host. Using a mouse model, strains of L. rhamnosus were tested to better understand mechanisms of protection against mercury as well as to examine potential modulation of host xenobiotic metabolism by probiotics. Data suggest it is possible to sequester mercury and prevent it from entering the bloodstream.

Collectively, these studies have increased our knowledge of probiotic mechanisms as well as lead to the development of novel applications of relevance to human health.

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