Indirect host and microbiota targets

Indirect host and microbiota targets refers to a therapeutic classification where the drug's effect is mediated through the commensal microbial community or indirect systemic pathways rather than a single host protein (Therapeutic Target Database, 2024). This category includes probiotics, prebiotics, and fecal microbiota transplants, which are primarily used to treat gastrointestinal and metabolic disorders by restoring microbial balance (Nature Reviews Drug Discovery, 2018). Instead of binding to a specific receptor, these interventions alter the microbial ecosystem, leading to the production of metabolites like short-chain fatty acids (SCFAs) that signal to the host's immune and metabolic systems (Cell, 2019). Because the therapeutic outcome depends on a complex network of host-microbe interactions, identifying a single canonical molecular target is often scientifically inappropriate. This classification is also applied to drugs like Metformin and Rifaximin, whose clinical efficacy is partially attributed to their impact on gut microbiota composition (Science Translational Medicine, 2020). As such, this classification represents a shift toward ecosystem-level pharmacology, focusing on biological states rather than individual molecules. The inherent complexity of the microbiome leads to significant inter-individual variability in treatment response, posing a challenge for standardized drug development. Monitoring microbial diversity and metabolite levels serves as a primary method for assessing the efficacy of these interventions. Overall, this category serves as a vital placeholder for therapies targeting the host-microbiome axis.

Other names

Unknown/indirect host and microbiota targetsMicrobiota-mediated targetsHost-microbiome axisNon-specific microbial targetsIndirect host targets

Modulation of the commensal microbial community composition and metabolic output to indirectly influence host physiological and immunological pathways.