Metabolic and Gut Microbiome Effects of a Remote Time-Restricted Eating and Mindfulness Intervention in Young Adults with Obesity: A Randomized Controlled Pilot Trial

Introduction: Obesity and chronic psychosocial stress (CPS) may drive early-onset colorectal cancer (EOCRC) through overlapping pathways, including disruption of the gut microbiome (reduced microbial diversity, overgrowth of pro-inflammatory microbial species, and altered metabolite production), which generates immune activation and persistent local and systemic inflammation. Methods: We conducted an 8-week randomized controlled pilot study evaluating time restricted eating (TRE) (ad libitum eating 12-8pm and fasting the remaining hours) and Mindfulness (“Mindfulness for Beginners” in the Calm.com app) among young adults (18-39 years old) with obesity (BMI ≥ 30 and ≤ 49.9 kg/m 2 ) and a Perceived Stress Score (PSS) ≥14 (indicating moderate to severe perceived stress). Individuals were randomized 1:1:1:1 to: TRE; Mindfulness; TRE & Mindfulness; or Control. We explored changes to the gut microbiome structure and composition using 16S amplicon sequencing (V4 region). We also measured serum-based tryptophan (TRP) and related metabolites, short-chain fatty acid (SCFAs), and systemic and intestinal inflammation. Results: Thirty-one (n=26 F) participants were included in the analysis who had stool and serum samples at both baseline and post-intervention. Mean age was 31.95 (±4.68) years, 16 participants were married/living with a partner, 14 were single/never married, and one was widowed. Over half of the participants (n=24) had completed graduate school or attained a professional degree. Twelve (39%) participants reported an annual household income of ≥ $80,000 US dollars. There was no statistically significant difference in alpha or beta diversity within or between study arms post-intervention. When assessing change in the relative abundance of taxa (genus-level) from baseline to post-intervention, all four groups had taxa that were differentially expressed between the two assessment periods. However, there was no clear pattern, likely because of the high individual variability of the gut microbiome. There was an inverse linear relationship in PSS difference between baseline and post-intervention in alpha (Shannon index) diversity (Adj R2=0.089; intercept=4.417; B=-0.0122; p=0.01), but not beta diversity. The Mindfulness and TRE & Mindfulness arms demonstrated decreases in circulating TRP, kynurenine, and kynurenic acid post-intervention suggesting a downregulation of the kynurenine pathway and an increase in circulating acetic acid. This was not the case in the TRE or Control arms. All three intervention arms had a decrease in circulating C-reactive protein at post-intervention, and only the TRE & Mindfulness arm had a decrease in fecal calprotectin, a marker of intestinal inflammation. Conclusion: Combined lifestyle interventions targeting both weight management and stress management may offer unique benefits for gut health in young adults with risk factors for EOCRC. Future research should investigate the clinical significance of these changes and their potential long-term impact on EOCRC risk reduction. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.