A Menu for Microbes: Unraveling Appetite Regulation and Weight Dynamics Through the Microbiota-Brain Connection Across the Lifespan

Am J Physiol Gastrointest Liver Physiol. 2025 Jan 15. doi: 10.1152/ajpgi.00227.2024. Online ahead of print.

Abstract

Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut microbiota-targeted approaches such as pre- pro- post- and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is (1) to provide an overview of the role of the microbiota-gut-brain-axis in appetite regulation across the lifespan and (2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.

Keywords: Appetite regulation; Obesity; Omics reward-related feeding behavior; gut microbiota; microbiota-gut-brain axis.