Abstract

Fasting is increasingly popular to manage metabolic and inflammatory diseases. Despite the role that the human gut microbiota plays in health and diseases, little is known about its composition and functional capacity during prolonged fasting when the external nutrient supply is reduced or suppressed. We analysed the effects of a 10-d periodic fasting on the faecal microbiota of fifteen healthy men. Participants fasted according to the peer-reviewed Buchinger fasting guidelines, which involve a daily energy intake of about 1046 kJ (250 kcal) and an enema every 2 d. Serum biochemistry confirmed the metabolic switch from carbohydrates to fatty acids and ketones. Emotional and physical well-being were enhanced. Faecal 16S rRNA gene amplicon sequencing showed that fasting caused a decrease in the abundance of bacteria known to degrade dietary polysaccharides such as Lachnospiraceae and Ruminococcaceae. There was a concomitant increase in Bacteroidetes and Proteobacteria (Escherichia coli and Bilophila wadsworthia), known to use host-derived energy substrates. Changes in taxa abundance were associated with serum glucose and faecal branched-chain amino acids (BCAA), suggesting that fasting-induced changes in the gut microbiota are associated with host energy metabolism. These effects were reversed after 3 months. SCFA levels were unchanged at the end of the fasting. We also monitored intestinal permeability and inflammatory status. IL-6, IL-10, interferon γ and TNFα levels increased when food was reintroduced, suggesting a reactivation of the postprandial immune response. We suggest that changes in the gut microbiota are part of the physiological adaptations to a 10-d periodic fasting, potentially influencing its beneficial health effects.

Highlights

  • Fasting is increasingly popular to manage metabolic and inflammatory diseases

  • When animals or humans switch from eating to periodic fasting, the source of energy for their cells switches from food molecules absorbed through the gastrointestinal tract to the utilisation of energy substrates mobilised out of several body tissues, primarily adipose tissue and body protein[6]

  • The Benjamini & Hochberg correction procedure was applied to control the false discovery rate[33]. The aim of this investigation was to describe the changes within the gut microbiota caused by a 10-d fast

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Summary

Introduction

Fasting is increasingly popular to manage metabolic and inflammatory diseases. Despite the role that the human gut microbiota plays in health and diseases, little is known about its composition and functional capacity during prolonged fasting when the external nutrient supply is reduced or suppressed. Changes in taxa abundance were associated with serum glucose and faecal branched-chain amino acids (BCAA), suggesting that fasting-induced changes in the gut microbiota are associated with host energy metabolism. These effects were reversed after 3 months. There is a metabolic switch in energy utilisation from glucose to fatty acids and ketones This increase in the rate of lipolysis and ketogenesis is reflected by a decrease in blood glucose, insulin, insulin-like growth factor-1, concomitant to an increase in glucagon, growth hormone, NEFA, ketone bodies and insulin-like growth factor binding protein-1 levels[4,7,8,9]

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