The Gut Microbiome
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A Knowledge of the gut microbiome accumulated unevenly across the human digestive tract. A striking report could establish that a pattern existed, yet it could not show whether microbial metabolism operated elsewhere. Researchers examining the gut microbiome therefore moved toward shared definitions and planned comparisons based on stool sequencing rather than discarding the earlier record. B For the present account of the gut microbiome, trillions of microorganisms live in the gut and interact with diet, medicines, immunity and one another. In microbial ecology and medicine, the term metabolite refers to a small molecule produced or used during metabolism. The definition gives researchers a common starting point for discussing the gut microbiome, but it does not identify a cause by itself. Two observations of the gut microbiome can share the label metabolite while differing in scale, timing or origin. C The evidence about the gut microbiome is informative but conditional. One point relevant to the gut microbiome is that microbial patterns are associated with many health states, but association alone rarely identifies a cause. Researchers test microbial metabolism as an explanation. Evidence reviewed for the gut microbiome shows that microorganisms transform food and host compounds into molecules that can affect local or wider physiology. Confidence in microbial metabolism rises when independent measures of the gut microbiome agree and rival explanations fail, rather than when a single comparison happens to be statistically precise. D Researchers rely chiefly on stool sequencing to investigate the gut microbiome. Research on the gut microbiome has found that genetic profiles are combined with diet records, metabolites and clinical measures because stool is only a proxy for the gut. They decide their comparison, exclusions and outcome measures for the gut microbiome in advance. A result about the gut microbiome is treated as stronger when it survives more than one source of evidence, not simply when one instrument measuring the gut microbiome reports many decimal places. E Practical programmes translate evidence about the gut microbiome into action. The discussion of the gut microbiome notes that researchers test diet, defined microbes or microbial products rather than assuming every diverse community is healthy. Their stated focus is treatment design. Teams working on the gut microbiome compare later outcomes with conditions before implementation and record unintended effects. This evaluation of the gut microbiome determines whether the original explanation involving microbial metabolism remains useful outside the research setting. F Interpretation of the gut microbiome must stop short of a universal claim. For the present account of the gut microbiome, results are sensitive to diet, medicine, geography and analysis, and effects from animals may not transfer directly to humans. Future work on the gut microbiome is organised around mechanism-led trials. For future research on the gut microbiome, mechanism-led trials will test specific organisms and products with pre-registered clinical outcomes. This use of mechanism-led trials targets a specific uncertainty about the gut microbiome rather than merely increasing the volume of data.