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

Mohr, Alex E., Sweazea, Karen L., Bowes, Devin A., Jasbi, Paniz, Whisner, Corrie M., Sears, Dorothy D., Krajmalnik-Brown, Rosa, Jin, Yan, Gu, Haiwei, Klein-Seetharaman, Judith, Arciero, Karen M., Gumpricht, Eric, Arciero, Paul J.·2024·Nature Communications
DOI 10.1038/s41467-024-48355-5PMC PMC11133430
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Abstract

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.

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  • Arciero et al. have shown superior body composition (reduced total body, fat, and visceral fat mass) with twice-weekly fasting compared with continuous energy restriction.

    “In contrast to these findings, Arciero et al. [4,70,71] have shown superior body composition (reduced total body, fat, and visceral fat mass) with TWF compared with CER.”

    From International Society of Sports Nutrition position stand: diets for body weight reduction (2026) · cites this paper as [4]

    The Results report greater losses of body weight and total, abdominal, and visceral fat mass with intermittent fasting–protein pacing than with continuous caloric restriction. But the intervention was a single 36–60-hour modified fasting period each week alongside higher protein intake, not twice-weekly fasting alone; the comparison does not isolate fasting from protein pacing. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • For the general population, a daily protein intake of 1.2-1.6 g/kg is appropriate for supporting physical activity and imparting preventive/clinical benefits to musculoskeletal, gut microbiome, and cardiometabolic health.

    “For the general population, a daily protein intake of 1.2–1.6 g/kg is appropriate for supporting physical activity and imparting preventive/clinical benefits to musculoskeletal, gut microbiome, and cardiometabolic health [4,92,101,105].”

    From International Society of Sports Nutrition position stand: diets for body weight reduction (2026) · cites this paper as [4]

    The Results report changes in body composition and gut-microbiome measures with intermittent fasting plus protein pacing in adults with overweight or obesity. The Methods describe protein as a percentage of calories, not a recommended daily intake of 1.2–1.6 g/kg. This intervention does not establish that the stated intake is appropriate for the general population or supports physical activity and all the listed health benefits. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • More recent trials by Arciero et al. found that a high-protein/high-frequency approach combined with 1-2 weekly modified fasting days (~500 kcal/day) was superior to conventional control diets for improving body composition in a caloric deficit, most likely driven by enhanced gut microbiome diversity and metabolomic signatures.

    “More recent trials by Arciero et al. [71,91] found that the latter approach (high-protein/high-frequency) combined with 1–2 weekly modified fasting days (~500 kcal/day) was superior to the conventional control diets for improving body composition in a caloric deficit, most likely driven by enhanced gut microbiome diversity and metabolomic signatures [4].”

    From International Society of Sports Nutrition position stand: diets for body weight reduction (2026) · cites this paper as [4]

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Authors
Mohr, A. E., Sweazea, K. L., Bowes, D. A., Jasbi, P., Whisner, C. M., Sears, D. D., Krajmalnik-Brown, R., Jin, Y., Gu, H., Klein-Seetharaman, J., Arciero, K. M., Gumpricht, E., & Arciero, P. J.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-05-28
Volume
15
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-024-48355-5
PMC
PMC11133430
Cited by
80
References
13
Language
en
Licence
Funders
Isagenix International LLC

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