The gut microbiome (GM) has a significant impact on body weight, composition and gastrointestinal function, therefore there is an increasing interest in dietary sources affecting microbes. A new study by researchers at Arizona State University shows promising effects of intermittent fasting versus continuous caloric restriction for healing the gut microbiome and weight management. This study explored the impact of two dietary regimens, Intermittent Fasting (IF) combined with Protein Pacing (IF-P) and Continuous Caloric Restriction (CR), on the Gut Microbiome (GM) and metabolic health in overweight/obese individuals over 8 weeks. This aimed to identify differences in faecal microbial and plasma metabolomic profiles.

The gut microbiome is highly responsive to nutritional input, and changing the content, and timing of meals can dramatically alter the profile and functional capacity of gut microbial species that influence responses. The interaction of IF-P for induced weight loss and GM is not completely understood yet. However, in this report of a randomised controlled trial, detailed interactions provide a novel view of GM-based precision nutrition advice for weight management and metabolic function.

This study involved 41 subjects (27 women, 14 men) aged 30-65 years with a BMI > 27.5kg/m2 who were randomised to either IF-P (n=21) or CR (n = 20). This eight-week intervention included dietary counselling, food records and GI symptom assessment. The IF-P regimen involved 4 protein pacing meals per day (25-50g protein/meal), and 36-60 weekly fasting periods. The CR regimen followed heart-healthy guidelines with an energy intake equivalent to that of IF-P. Stool samples were assayed for GM profiles, blood plasma cytokines and metabolomics, with further subgrouping and longitudinal analyses.

The results of this study came out as follows: IF-P treated only participants produced favourable changes in their GM, such as alleviated gut symptomatology and increased metabolic features. By contrast, CR up-regulated metabolites that are involved in longevity-related pathways.

IF-P also dramatically increased several cytokines associated with lipolysis, weight loss, and automatic immune response. The analysis of metabolic pathways revealed significant alterations including glycine, serine, threonine metabolism, alanine, aspartate and glutamate metabolism, with changes in these pathways indicating fat mobilisation.

Similar to CR, IF-P resulted in significant weight loss and reduction in fat mass. However, IF-P found a larger fat decrease with an average of 8.81% lost over the 8 weeks compared to 5.4% on CR. The researchers believed the interaction between faecal samples and plasma metabolomic data activated a more robust comic signature, reflecting a stronger probiotic effect and diversity impacting IF-P over CR.

Finally, these findings were supported during a responder analysis, in which high weight loss responders had a higher prevalence of beneficial gut microbes and pathways, as well as improved faecal expression central to lipid metabolism. Low weight loss responders exhibited elevated butyrate-producing species and pathways involved in peptide metabolism.

This study underscores the potential of IF-P in improving gut health alongside weight management. While further research is needed, these findings show a promising insight into effective dietary interventions for treating obesity and metabolic disorders. Also, it shows how continuous caloric restriction might not be the only method for healthy and sustainable weight loss.

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1. 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. Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-48355-5