Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

The gut microbiome (GM) modulates body weight/composition and gastrointestinal function; thus, approaches targeting resident gut microbes have attracted interest. Intermittent fasting (IF) and protein pacing (P) regimens facilitate weight loss (WL) and improve body composition, but their interrelationships with the GM are unclear. In a randomized controlled study, we compared combined IF-P (n = 21) versus heart-healthy continuous calorie restriction (CR, n = 20) matched for energy intake over 8 weeks in adults with overweight/obesity. IF-P yielded improved gut symptomatology and increased abundance of Christensenellaceae, along with higher circulating cytokines and amino acid metabolites favoring fat oxidation (p < 0.05). CR increased metabolites linked to a longevity-related pathway (p < 0.05). Despite similar weekly energy intake and physical activity, IF-P produced greater WL and favorable body composition changes. Findings indicate GM and metabolomic factors contribute to WL maintenance and body composition. This work provides insight into the GM and metabolomic profiles following IF-P or CR and highlights differences in microbial assembly associated with WL responsiveness. These data may inform GM-focused precision nutrition with larger, longer studies. Trial registration: NCT04327141.

Alex E. Mohr, Karen L. Sweazea, Devin A. Bowes, Paniz Jasbi, Corrie M. Whisner, Dorothy D. Sears, Rosa Krajmalnik-Brown, Yan Jin, Haiwei Gu, Judith Klein-Seetharaman, Karen M. Arciero, Eric Gumpricht, Paul J. Arciero