Abstract
The gut microbiome is a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a crucial role in human health. It interacts with various host physiological processes, while also interacts with various drugs. This thesis explores the interplay between the gut microbiome and common prescription drugs, examining how medications influence microbial composition and function, and faecal metabolites that serve as functional readouts of the gut microbiome.The aim of the thesis is to enhance the knowledge of drug-microbiome interactions and understand potential drug side effects. Besides, to uncover boarder patterns of drug-metabolite interactions and provide another layer of complexity to our understanding of drug interactions.
The first part of the thesis investigates the relationship between serum vitamin B12 levels and the gut microbiomes, revealing a negative association between serum folate levels and the alpha diversity of the gut microbiome, and specific microbial genus associated with vitamin B12 levels, highlighting the influence of micronutrients on microbial populations.
Next, the analysis focused on a common drug, Proton Pump Inhibitors (PPIs), and assessed the impact of this drug on bone mineral density, exploring whether this effect is mediated through alterations in the gut microbiome or the host's metabolic environment. Although no mediation effect was observed via the microbiome, PPI use correlated with significant changes in both the microbiome and plasma metabolites, suggesting alternative pathways through which these drugs could affect bone health.
Expanding on these themes, the next analysis investigates the broader impacts of common prescription drugs on microbial features. Significant associations between drug use and changes in microbial diversity, composition, and specific metabolic functions were identified.
These findings highlight the potential for drugs to induce substantial shifts in microbial communities, which may influence drug metabolism and therapeutic outcomes.
Finally, the analysis incorporates faecal metabolomics data to reveal the metabolic changes in drug users. A variety of drugs were associated with specific metabolites, reflecting the direct impact of drug action or disease state on both host and microbial metabolic activities.
These metabolites may act as biomarkers for assessing drug efficacy and tolerance, providing insight into the complex interactions among drugs, the gut microbiome, and host metabolism.
In summary, the thesis underscores the importance of considering the gut microbiome within the context of pharmacological treatments, suggesting that a deeper understanding of these interactions is essential for refining therapeutic approaches and tailoring personalised medicine.
| Date of Award | 1 Jan 2025 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Mario Falchi (Supervisor) & Tim Spector (Supervisor) |