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Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity

  • Mohr, Alex E.1
  • Jasbi, Paniz1, 2
  • Bowes, Devin A.3
  • Dirks, Blake3
  • Whisner, Corrie M.1, 3
  • Arciero, Karen M.4
  • Poe, Michelle4
  • Gu, Haiwei1, 5
  • Gumpricht, Eric6
  • Sweazea, Karen L.1, 7
  • Arciero, Paul J.4
  • 1 College of Health Solutions, Arizona State University, Phoenix, AZ , (United States)
  • 2 School of Molecular Sciences, Arizona State University, Tempe, AZ , (United States)
  • 3 Center for Health Through Microbiomes, The Biodesign Institute, Arizona State University, Tempe, AZ , (United States)
  • 4 Human Nutrition and Metabolism Laboratory, Department of Health and Human Physiological Sciences, Skidmore College, Saratoga Springs, NY , (United States)
  • 5 Center for Translational Science, Florida International University, Port St. Lucie, FL , (United States)
  • 6 Isagenix International, LLC, Gilbert, AZ , (United States)
  • 7 School of Life Sciences, Arizona State University, Tempe, AZ , (United States)
Published Article
Frontiers in Nutrition
Frontiers Media SA
Publication Date
Oct 26, 2022
DOI: 10.3389/fnut.2022.1036080
  • Nutrition
  • Original Research


Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial ( ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.

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