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Intermittent fasting modulates gut microbiota and improves obesity and host energy metabolism

A small study in humans found that #IntermittentFasting modulates the intestinal #microbiota & improves #obesity & host energy #metabolism. The study found enrichment of #Parabacteroides distasonis & #Bacteroides thetaiotaomicron after the intervention.

Abstract Intermittent fasting (IF) is a promising paradigm for weight loss which has been shown to modulate the gut microbiota based on 16S rRNA gene amplicon sequencing. Here, 72 Chinese volunteers with a wide range of body mass index (BMI) participated in a three-week IF program during which an average loss of 3.67 kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembly yielded 2934 metagenome-assembled genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and atherosclerotic cardiovascular diseases (ASCVD). MAGs enriched after the intervention showed high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.

Introduction With the economic development and spread of modern Western diets and lifestyles, obesity has become a worldwide problem1. Compared to 1980, the obese population doubled in 2015, including 107.7 million children and 603.7 million adults. Moreover, more than 60% of 4 million annual global deaths have been related to obesity2. As a chronic metabolic disorder, obesity is known to be a predisposing factor for type 2 diabetes3,4, cardiovascular disease4, and several types of cancer5. To treat obesity and prevent associated diseases, different types of interventions have been applied and studied, including surgery, medication, exercise, and fasting. As one strategy of fasting, intermittent fasting (IF) has shown consistent performance in relation to weight loss and relevant clinical improvements, attracting public attention in recent years6. A randomized controlled trial using a parallel-group design involving 115 obese women showed an average weight loss of 4 kg after a three-month IF intervention, whereas the average weight loss with traditional energy restriction by contrast was 2.4 kg. Moreover, the reduction in insulin resistance after IF (0.34 units in average) was greater compared to traditional fasting programs (0.20 units in average)7. Other studies also reported that the performance of IF intervention was better than that of physical training programs8,9. According to these results, IF holds promises as an option to counteract obesity. However, as most studies have been performed in obese western populations, it has not been well addressed whether IF intervention is beneficial for East-Asian populations or individuals with normal body weight and body fat. The gut microbiota plays a significant role in obesity and associated diseases10,11. Changes in the composition and function potential of the gut microbiota can either prevent or promote obesity by stimulating the absorption of nutrients and regulating host metabolism12,13,14,15. Therefore, remodeling of the gut microbiota becomes an attractive strategy for the prevention and treatment of obesity16,17. Interplay between the gut microbiota and dietary habits has also been studied. Type and time of food intake were reported to modify the diurnal rhythm of the gut microbiota18,19,20. A previous study in mice also suggested that alterations in the gut microbiota in response to every-other-day fasting were associated with browning of white adipose tissue and a decrease in blood pressure21,22. However, IF-induced change in the human gut microbiota, especially at the species level, is not well characterized, and details on how this change may promote weight loss remain unclear. In this study, we performed a three-week IF intervention in 72 Chinese adult participants with different body weights, ranging from regular to obese, and revealed pronounced improvements in multiple clinical parameters, including body weight, body mass index (BMI), and the atherosclerosis index (AI). IF-induced changes in the taxonomic composition and functional potential of the gut microbiota, and correlation between these changes and the clinical improvements were investigated based on a shotgun metagenomic sequencing approach. The results suggested that a short-term 5:2 IF intervention induced significant changes in the composition and functional potential of the gut microbiota in a baseline independent manner, associated with an increase in the relative abundance of species considered beneficial, including Parabacteroides distasonis and Bacteroides thetaiotaomicron, which may confer weight loss and improvements in host metabolism through the synthesis, and secretion of beneficial metabolites. Read more at:

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