FIGURE 3.

Framework for future studies on the relation between energy metabolism and the gut microbiome. 1) Longitudinal observational studies can be used to assess how gut microbiome changes in long term and how those changes are related to health outcomes; 2) Randomized controlled trials can test hypotheses generated from longitudinal studies in well-controlled settings; 3) Energy expenditure should be assessed by indirect calorimetry, preferably metabolic chamber, and/or doubly labeled water; 4) gut microbiome composition should be assessed by metagenomic sequencing and its functions should be assessed by analyzing its metabolites and by multiomics; 5) Results from human studies should be analyzed using advanced analytical methods to infer possible causations and mechanisms; 6) Those findings can be translated into animal models with human associated microbiome and monocolonization to confirm causation and mechanisms. Abbreviations: REE, resting energy expenditure; TEE, total energy expenditure; SCFAs, short-chain fatty acid; LPS, lipopolysaccharides.