Abstract: Predicting a weight loss potential from gut microbiome data is described herein. In an example, a system accesses gut microbiome metagenomic sequence data for a subject and determines a measurement of one or more weight loss features from the gut microbiome metagenomic sequence data. The one or more weight loss features define a gut microbiome signature for weight loss response for the subject independent of a body mass index of the subject. The system determines a weight loss potential for the subject based on a comparison of the measurement of the subject to a plurality of reference measurements of the one or more weight loss features for a reference population showing variable weight loss responses. The system outputs the weight loss potential for the subject.