Ecology of amino acid auxotrophic bacteria in the human gastrointestinal tract
The pathophysiology and pathogenesis of several metabolic and inflammatory diseases is associated with specific taxa within the human gut microbiome and the microbial amino acid metabolism. However, these ecological changes remain still poorly understood. Studying amino acid auxotrophic bacteria, which are incapable of the de novo synthesis of vital nutrients like amino acids and known to influence the ecology of microbial systems, could improve the understanding of ecological imbalances of the human gut microbiome in diseases. In this thesis, the distribution of amino acid auxotrophies is characterized in small and large intestinal microbiomes in non-dysbiotic and dysbiotic states. The prediction of auxotrophies is based on genome-scale metabolic modeling. Furthermore, the influence of auxotrophic bacteria on the diversity and long-term stability of the gut microbiome is analyzed. This thesis revealed that auxotrophies in the human gut microbiome are ubiquitous. Auxotrophies for human-essential amino acids, especially tryptophan, are most common. In non-dysbiotic states, auxotrophies are more abundant in the small intestine than the large intestine but decreased in small intestinal bacterial overgrowth. In addition, auxotrophic bacteria were found to positively influence the diversity and long-term stability of the gut microbiome. Validation of the predicted auxotrophies using genome-scale metabolic models against experimentally confirmed auxotrophies demonstrated an accuracy of over 90%. These findings have implications for understanding microbial ecology in gut health and may inform future strategies to modulate the gut microbiome in diseases.
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