Date of this Version
Krumbeck, Janina. "Characterization of the Role of Host and Dietary Factors in the Establishment of Bacteria in the Gastrointestinal Tract." (2016).
Probiotic bacteria and synbiotics are used as therapeutic and prophylactic agents. The majority of probiotic and synbiotic applications contain bacterial strains that are allochthonous to the human gastrointestinal (GI) tract. Accordingly, many bacterial strains do not survive digestion, or are not capable of persisting and competing the resident gut microbiota, and are therefore washed out of the GI tract shortly after the treatment is discontinued. This might reduce the health effects of these treatments. Therefore, research is needed to address the ecological challenges that probiotic strains encounter in the GI tract in order to develop probiotic regimens. Determining which ecological factors are limiting the colonization of bacteria remains a challenge. To gain insight into the complex interplay between host and microbe, we chose Lactobacillus reuteri and its rodent host as a model to investigate which genes of L. reuteri contribute to tolerance towards host gastric acid secretion. We established the urease cluster as the predominant factor in mediating resistance to gastric acid, and a mutation of this cluster resulted in substantially decreased population levels of L. reuteri in mice.
Secondly, we established a method to select for synergistic synbiotic combinations. Based on in vivo selection (IVS), autochthonous putative probiotic strains are enriched in the GI tract of subjects by the continued consumption of a prebiotic. We used IVS to select a strain of Bifidobacterium adolescentis that became enriched in a human feeding trail with galactooligosaccharides (GOS). Here we have shown that the synbiotic combination of Bifidobacterium adolescentis IVS-1 and GOS significantly enriched for the putative probiotic component in rats. IVS-1 became the most dominant operational taxonomic unit in the GI tract, outcompeting the resident Bifidobacterium species. Similarly, we tested this synbiotic in a human trial with obese adults. In this random, placebo-controlled parallel arm study, the synbiotic combination of IVS-1 and GOS led to establishment of IVS-1 in significantly higher numbers in the GI tract than a commercial synbiotic.
Together, the studies presented in this dissertation allowed new insights into the colonization factors of a true GI symbiont, which could contribute to the development of improved probiotics, and provided novel insight into a rational selection of probiotics and synbiotics.
Advisors: Robert W. Hutkins and Jens Walter