We report a weight-loss response analysis on a small cohort of individuals (N=25) selected from a larger population (N[~]5,000) enrolled in a commercial scientific wellness program, which included healthy lifestyle coaching. Each individual had baseline data on blood metabolomics, blood proteomics, clinical labs, lifestyle questionnaires, and stool metagenomes. A subset of these participants (N=15) lost at least 10% of their body weight within a 6-12 month period and saw significant improvement in metabolic health markers ( weight loss group), while another subset of individuals (N=10) undergoing the same lifestyle intervention showed no change in BMI over the same timeframe ( no weight loss group). Only a single baseline blood analyte, a metabolite linked to fried food consumption, was (negatively) associated with weight loss, but a large number of baseline stool metagenomic features, including complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, cell wall synthesis genes, and gut bacterial replication rates, were significantly associated with weight loss after explicitly controlling for baseline BMI. Together, these results provide a set of baseline gut microbiome functional features that are associated with weight loss outcomes.

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