Changes in Human Gut Microbiota Composition Are Linked to the Energy Metabolic Switch During Ten Days of Fasting

Background: Fasting has been documented to have therapeutic benefits. Any consequence of the drop in external nutrient supply to the human gut microbiota during prolonged periods of fasting is unknown. Methods: We analysed the effects of a ten-day periodic fasting on the human gut microbiota in an observational study including 15 healthy men. We also monitored the energy metabolic switch from carbohydrates to fatty acids and ketones, parameters of intestinal permeability, inflammatory status, and well-being. Participants fasted according to the peer-reviewed Buchinger therapeutic fasting guidelines with a daily caloric intake of 200-250 kcal. Findings: 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 sequences showed that fasting caused a large decrease in the relative 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 and in particular to ferment aminoacids. BCAA production increased during the fast. Changes in taxa abundance were associated with serum glucose and faecal BCAA, suggesting that fasting-induced changes in gut microbiota are associated to host energy metabolism. These effects were reversed after three months. Although SCFA levels were not changed at the end of the ten-day fasting period, their levels were increased after three months. The levels of four cytokines (IL-6, IL-10, IFNγ, TNFα) increased when food was reintroduced, suggesting that food intake reactivated the postprandial immune response. Interpretations. We reveal that changes in faecal microbiota composition of healthy subjects during ten days of fasting are associated with energy metabolism. This suggests that the gut microbiota plays a role in physiological adaptations to a ten-day periodic fasting, potentially influencing its beneficial health effects. Clinical Trial Registration: German Clinical Trials Register (DRKS-ID: DRKS00011165, 24/10/2016). Funding Statement. The study was financed by Amplius GmbH, Uberlingen, Germany. This company has the task to develop a research department for the Buchinger Wilhelmi Clinics Uberlingen and Marbella who are the funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. Declaration of Interests: FWT is managing director of Amplius GmbH, that is in charge of the scientific documentation for BWC. Amplius GmbH is a company that conceives, coordinates and develops fasting research. All authors declare that no competing interest exist. Ethics Approval Statement: This study was approved by the medical council Baden-Wurttemberg (application number: F-2016-090, 27/09/2016) and registered at the German Clinical Trials Register (DRKS-ID: DRKS00011165, 24/10/2016). It was conducted at the Buchinger Wilhelmi clinic (BWC) in Uberlingen (Germany), in accordance with the principles of the Declaration of Helsinki between 20/11/2016 and 10/12/2016.