Proteome modifications of gut microbiota in mice with activity-based anorexia and starvation – role in ATP production

Abstract Objective Activity-based anorexia (ABA) in rodents is a behavioral model of anorexia nervosa, both characterized by negative energy balance, hyperactivity and dysbiosis of gut microbiota. Gut bacteria are known to produce energy substrates including adenosine triphosphate (ATP) and acetate. Here we studied whether ABA may alter the proteome of gut microbiota relevant to ATP and acetate productions. Methods The ABA was developed in male mice and compared with food-restricted and ad libitum-fed conditions. Proteomic analysis of faeces was performed using the 2-dimentional gel electrophoresis and mass spectrometry. The in vitro ATP-producing capacity of proteins extracted from faeces was assayed. Results Increased level of the phosphoglycerate kinase, an ATP-producing glycolytic enzyme was detected in faeces of food-restricted mice and this enzyme was further increased in the ABA group. Starvation also upregulated several other proteins synthetized by order Clostridiales including Clostridiaceae and Lachnospiraceae families. No significant differences in the in vitro ATP producing capacity by bacterial proteins from ABA, food-restricted and ad libitum-fed control mice were found. However, plasma levels of acetate strongly tended to be increased in the activity groups including ABA mice. Conclusion The data reveal that starvation in food-restricted and ABA mice induces proteome modification in gut bacteria favoring ATP production mainly by the order Clostridiales. However, this does not result in increased total ATP-production capacity by gut microbiota. These changes can be interpreted as an adaption of specific gut bacteria to the host malnutrition beneficial for host survival.