Microbial Therapeutics: A Translational Approach to Combat Metabolic Diseases

The human microbiota, its functional profiling, and metabolome have gained substantial attention in biomedical research due to their critical roles in host-microbe interactions that significantly influence health and disease states. Emerging evidence highlights that the crosstalk between the host and the microbiota orchestrates essential physiological processes, including metabolism, immune regulation, and barrier integrity. Imbalance, characterized by alterations in microbiota composition and functional potential, is increasingly implicated in numerous diseases, thus positioning microbial signatures as potent biomarkers and therapeutic targets. Multi-omics analyses, integrating metagenomics, metabolomics, proteomics, and transcriptomics, represent a transformative approach to microbiome research, facilitating comprehensive insights into microbial functionality and metabolic pathways. Combined with extensive in vitro and in vivo experimentation, such approach enhances clinical translation by identifying precise microbial metabolites and functions as novel intervention targets, ultimately paving the way for microbiome-based therapeutic strategies.

Within this context, the escalating global cardiometabolic disease crisis underscores the urgent necessity for innovative therapeutic interventions. The present thesis addresses this critical gap by leveraging advanced omics methodologies to dissect microbial metabolic contributions in two major metabolic conditions: Metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity. Through extensive experimental validation, we identify key microbial metabolic
targets potentially implicated in disease pathogenesis, elucidating their roles in metabolic dysregulation. Furthermore, this research pioneers the design, development, and evaluation of targeted microbial therapeutics, harnessing precise modulation of microbial metabolism. These efforts aim to establish robust, clinically actionable microbiome-based therapies, significantly contributing to addressing the current cardiometabolic epidemic.