Abstract
The early stages of the metagenomics era produced countless observational studies linking various human diseases to alterations in the gut microbiota. Only recently have we begun to decipher the causal roles that gut microbes play in many of these conditions. Despite an incomplete understanding of how gut microbes influence pathophysiology, clinical trials have tested empirically numerous microbiota-targeting therapies to prevent or treat disease. Unsurprisingly, these trials have yielded mixed results. Nonetheless, the consumer market for probiotics, prebiotics, and synbiotics continues to grow. This theme paper highlights recent discoveries of mechanisms underlying diet-microbial-host interactions as they pertain to growth and metabolism and discusses current and future applications of microbiota-targeting therapies in the context of child malnutrition as well as obesity and its metabolic comorbidities, including nonalcoholic fatty liver disease and cardiovascular disease. We also highlight current challenges and identify future directions to facilitate a more efficient and direct path to clinical impact.