Protein interval fasting is better than calorie restriction for gut health and weight loss

In a recent study published in the journal Nature Communications, researchers compared the effects of intermittent fasting with a protein-focused diet (IF-P) with heart-healthy calorie restriction (CR) on gut microbiota remodeling and metabolic profiles.

The gut microbiome plays a key role in weight management and digestive health. Diets that influence both the gut microbiota and weight have therapeutic potential for regulating metabolic disorders.

Recent preclinical studies in mice have shown that protein intake can reduce adiposity following chronic fatty liver disease. IF-P, for example, is a successful strategy for weight loss and body composition; however, the impact of this approach on the gut microbiome remains unclear.

The current study was conducted in Saratoga Springs, New York. It included people who were either sedentary or moderately active, overweight or obese, maintaining a stable weight, and aged 30 to 65 years. Participants were randomly assigned to the IF-P or CR groups, which included 21 and 20 people, respectively, for eight weeks.

Caloric intake and expenditure were matched for all study participants. Individuals using antibiotics, antifungals, or probiotics in the past two months were excluded from the study.

Faecal, microbial, and plasma metabolic characteristics were assessed in overweight or obese individuals following either the IF-P or CR diet. Changes in food intake, body weight, cardiometabolic parameters, hunger scores, and gut microbiota were also documented in each group. Study participants completed the Gastrointestinal Symptom Rating Scale (GSRS) at baseline and at weeks 4 and 8.

Faecal samples were collected for deoxyribonucleic acid (DNA) extraction and quantitative polymerase chain reaction (qPCR) analysis to determine total bacterial biomass and faecal microbiota composition. Study participants also provided blood samples for body composition assessment, biochemical assessment, and serum metabolite analysis, which was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-MS for short-chain fatty acid (SCFA) analysis.

The effects of IF-P on intestinal bacterial colonization, stool parameters, and caloric restriction were determined using 16S ribosomal RNA (rRNA) sequencing and linear mixed effects modeling to identify patterns of covariation and co-occurrence between the microbiota and circulating metabolites. Multiomics factor analysis also allowed the researchers to identify patterns of covariation and co-occurrence between the microbiome and circulating metabolites.

The protein diet includes four meals containing 25-50 grams of protein each day, while IF-P includes 35% carbohydrates, 30% fat, and 35% protein for five to six days a week. The CR regimen includes 41% carbohydrates, 38% fat, and 21% protein, in line with U.S. dietary guidelines.

Study participants received supplements and snacks on IF days, while protein days included four to five meals each day, based on the American Heart Association's National Cholesterol Education Program lifestyle modification recommendations.

IF-P had a greater effect on GI symptoms, gut microbiota diversity, and circulating metabolites than CR. Additionally, IF-P resulted in increased abundance of Marvinbryantia, Christensenellaceae, and Rikenellaceae, as well as levels of cytokines and amino acid metabolites that promote fatty acid oxidation.

IF-P significantly increased levels of cytokines involved in lipolysis, inflammation, weight loss and immune response, such as interleukin-4 (IL-4), IL-6, IL-8 and IL-13. While caloric restriction increased levels of metabolites involved in a metabolic pathway associated with longevity.

Gut microbiota and metabolic variables influenced weight loss maintenance and body composition. In addition, IF-P had a greater impact on gut microbiota dynamics than caloric restriction.

IF-P also reduced total fat, carbohydrate, salt, sugar, and calorie intake by 40% while increasing protein intake to a greater extent than CR. Study participants on IF-P lost more body weight, total, abdominal, and visceral fat, and had a higher percentage of lean mass. Participants in the IF-P group also demonstrated a significant 33% reduction in visceral fat.

IF-P was associated with significant improvements in GI symptoms, increased levels of Christensenella, a gut bacteria associated with a lean phenotype, and circulating cytokines that regulate overall body weight and fat loss. The study results highlight the importance of individualized dietary interventions for optimal weight management and metabolic health.

However, further research is needed to understand the processes responsible for these observations and the therapeutic implications of establishing individualized methods for obesity control. These findings may also guide future recommendations for precision diets targeting the gut microbiome, with larger sample sizes and longer study durations.