A researcher is investigating how the gut microbiome influences the efficacy of a new immunotherapy for cancer patients. They hypothesize that certain microbial compositions may enhance the response to treatment. Which challenge related to microbiome research must the researcher address to effectively utilize their findings in a clinical setting?

Researchers must tackle the problem of causality versus correlation in microbiome studies. They need to show that a particular microbial community actually improves immunotherapy response, not just co‑occurs with it, by using controlled experiments and longitudinal data. Demonstrating this requires standardized sampling, sequencing, and statistical methods that can isolate the effect of specific microbes from host genetics and diet. For example, a study that shows patients whose gut is enriched in *Bifidobacterium* respond better only if the enrichment is experimentally induced and improves outcomes. Without proving causality, clinicians cannot reliably translate microbiome findings into treatment decisions.