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Intermittent Fasting Promotes a Healthy Gut Microbiome, Study Finds

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Intermittent fasting and a diet incorporating a protein-pacing regimen can lead to better gut health, increased metabolism and weight loss, according to a new study.

Arizona State University (ASU) researchers compared the effects of a heart-healthy, calorie-restricted diet (based on U.S. Department of Agriculture, USDA, dietary recommendations), and a calorie-restricted regimen incorporating intermittent fasting and protein pacing. They concluded that the latter diet increases gut microbes associated with a lean phenotype and circulating cytokines that mediate total body weight and fat loss.

The findings, published in the journal Nature Communications, provide valuable insights into the complex relationship between diet, the gut microbiome and metabolism and could lead to improved strategies for combatting obesity.

Healthy diet, healthy gut

The gut microbiome refers to the trillions of microbial cells, including bacteria, fungi, viruses, bacteriophage and protozoa that reside in the gastrointestinal tract. The gut microbiome's influence on human health and disease is well documented, with these organisms playing a role in enhancing or impairing metabolic and immune functions.

“The gut bacteria influence how we store fat, balance glucose levels and respond to hormones that make us feel hungry or full,” said Karen Sweazea, the ASU principal investigator of the study.

“Disruptions in the gut microbiota can lead to increased inflammation, insulin resistance and weight gain, underscoring the critical role of gut health in preventing and managing metabolic disorders.”

Intermittent fasting (an eating pattern that cycles between periods of fasting and eating) and protein pacing (controlled protein intake at specific meals) have recently gained popularity for their potential health benefits, including weight loss, improved metabolic health and enhanced brain function. However, the effects of these dietary modifications on the gut microbiome have remained unclear.

The new study involved 27 female and 14 male participants who were overweight or obese (BMI > 27.5 kg/m2; % body fat > 30%).

One group of participants was assigned to protein-pacing intermittent fasting, which consisted of 4-5 meals per day on non-fasting days with fixed amounts of protein and 350-550 kcal on the 2 fasting days per week. The other group adhered to a heart-healthy, calorie-restricted diet. Both groups were monitored over eight weeks for changes in fecal microbial and plasma metabolomic signatures.

Following the intermittent fasting and protein-pacing regimen, participants experienced increased beneficial gut bacteria, particularly Christensenellaceae microbes, and higher levels of circulating cytokines and amino acid metabolites that favored fat oxidation. In contrast, the calorie-restricted group showed increased metabolites linked to longevity-related pathways.

Despite both groups having similar average weekly energy intake and physical activity energy expenditure during the study, the intermittent fasting and protein-pacing group lost significantly more body weight in comparison to those on a calorie-restricted diet (8.81% vs 5.4%).

Participants who followed the intermittent fasting and protein-pacing diet experienced reductions in overall body fat, including belly fat and deep abdominal fat, and saw an increase in the percentage of lean body mass.

Before individuals are inspired to try and follow a similar diet, Dr. Duane Mellor, dietitian and spokesperson for the British Dietetic Association; and honorary academic fellow at Aston University, British Dietetic Association (BDA), warned, “This diet was carefully designed, with the protein pacing intermittent fasting approach involving a number of supplements provided by the study funder, therefore this is not a diet that is easy to follow using food from the market or supermarket.”

Managing weight one microbe at a time

The findings highlight the potential for personalized approaches to dietary interventions for optimal weight management, the researchers concluded.

“While limited in duration and sample size, this comprehensive investigation — which included the analysis of the gut microbiome, cytokines, fecal short-chain fatty acids and blood metabolites — underscores the intricate interplay between diet, host metabolism and microbial communities,” said Alex Mohr, lead author of the study.

Mohr says further research will be necessary to elucidate the underlying mechanisms driving these associations – a sentiment Mellor shares.

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“While it is an interesting study, suggesting protein pacing and intermittent fasting help to support weight loss, as shown in a study published in 2023, in this analysis this appeared to be linked to improved gut bacteria levels,” said Mellor. “However, it is unclear if this is an effect of the higher protein levels in the protein pacing and intermittent fasting, the effect of the intermittent fasting or both, alternatively it could have been an effect of the extra fiber in this diet.”

Future studies should also consider investigating microbial populations in upper gastrointestinal sections, the researchers suggest, alongside potential intestinal tissue remodeling to gain a more comprehensive understanding of the gut microbiome’s role in personalized weight interventions.

Reference: Mohr AE, Sweazea KL, Bowes DA, et al. Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction. Nat Commun. 2024;15(1):1-20. doi: 10.1038/s41467-024-48355-5

This article is a rework of a press release. Material has been edited for length and content.