Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Crawford, Jason
Abstract
Human hosts receive signals from the body indicating their degree of health, especially during homeostatic disruption. However, these signals are received at the end of a long line of communication between host, host response, microbiome, and metabolites. Immune system response, inflammation, and disease can be triggered by complex crosstalk mechanisms. The microbiome, home to trillions of microorganisms, can interact with other microbial members, utilize surrounding synthetic machinery, or directly modulate host response. Metabolites produced by the microbiome or sourced from the diet can also partake in host, bacterial, and metabolic crosstalk. Further, each can be influenced by their environment, such as antibiotic or nutrient availability, adding layers of complexity to host signaling. This graduate work has characterized small molecule crosstalk mechanisms with diverse roles in human health. Chapter 1 discusses the microbiome and its role in bidirectional host-bacteria crosstalk. Chapter 2 highlights metabolites produced at the intersection of colibactin and FAS. Chapter 3 details bacterial-metabolite interactions with a role in mediating pathogenicity. Chapter 4 investigates bacterial metabolic processing by human cytochrome P450s. Chapter 5 comments on exploiting host-bacterial interactions for therapeutic expansion. Through exploration of the human microbiome’s mechanistic and metabolomic crosstalk complexities, a more complete understanding of the microbial-host ecosystem can take shape, which scientists can leverage to support health and guide therapeutic advancements.
Recommended Citation
Turocy, Tayah, "Molecular Crosstalk Mechanisms: Small Molecules Involved in Host-bacterial Interactions" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1420.
https://elischolar.library.yale.edu/gsas_dissertations/1420
