Assessing the Effects of Intermittent Fasting and Calorie Restriction on the Gut Microbiome

Evidence suggests that the composition of the gut microbiome is as influential on long-term health as choices in diet and exercise. The relative proportions of microbial species shift with age, favoring harmful pro-inflammatory microbes over those that produce beneficial metabolites. It is reasonable to ask how much of the beneficial effects of fasting and calorie restriction are mediated via the gut microbiome, via slowing or reducing age-related changes in these microbial populations. With that in mind, researchers are beginning to assess how fasting and calorie restriction alter the behavior and balance of microbial populations making up the gut microbiome. The paper here is one example of this sort of study.

As a principal modulator of the gut microbiome (GM) and weight status, nutritional input holds great therapeutic promise for addressing a wide range of metabolic dysregulation. The GM must regulate its growth rate and diversity in response to nutrient availability and population density. Such maintenance is affected by caloric restriction (CR) coupled with periods of feeding and intermittent fasting (IF). The current study incorporates protein pacing (P), defined as four meals/day consumed evenly spaced every 4 hours, consisting of 25-50 g of protein/meal. Indeed, we have previously characterized a dietary approach of calorie-restricted IF-P combined and P alone.

In this current work, we compare the effects of two low-calorie dietary interventions matched for weekly energy intake and expenditure; continuous caloric restriction on a heart-healthy diet (CR) aligned with current United States (US) dietary recommendations versus our calorie-restricted IF-P diet. 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, whereas metabolites associated with a longevity-related metabolic pathway increase with CR. The plasma metabolome analysis revealed distinct metabolite signatures in IF-P and CR groups, with the convergence of multiple metabolic pathways. Differences indicate GM and metabolomic factors play a role in weight loss maintenance and body composition. This data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration.


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