Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults.

Background: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.

Method: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.

Results: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations. Notably, certain bacteria taxa exhibited complex interactions and strong correlations with serum metabolites implicated in energy and amino acid metabolism, with a particular focus on fatty acylcarnitines and tryptophan derivatives. A key focus of our study was the effect of , which was highly increased during CF and exhibited a strong correlation with fat metabolic indicators. This bacterium was found to mitigate high-fat diet-induced obesity, glucose intolerance, dyslipidemia, and intestinal barrier dysfunction in animal experiments. These effects suggest its potential as a probiotic candidate for the amelioration of dyslipidemia and for mediating the benefits of fasting on fat metabolism.

Conclusions: Our pilot study suggests that alterations in gut microbiota during CF contribute to the shift of energy metabolic substrate and the establishment of a novel homeostatic state during prolonged fasting.