Weight loss response following lifestyle intervention associated with baseline gut metagenomic signature in humans

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. ### Competing Interest Statement Jennifer Lovejoy currently works at the Lifestyle Medicine Institute. Nathan Price currently works at Onegevity. Both companies are involved in precision medicine and scientific wellness, but neither stand to gain financially from the work in this manuscript. All other authors declare not competing interest.