Letter to the Editor: The Gut Microbiome–Endocrine Axis in Obesity: Mechanisms and Therapeutics

ABSTRACT

Obesity therapeutics is rapidly evolving, and mechanistic frameworks linking the gut microbiome to systemic metabolism are essential for clinical translation. In this letter, I commend the invited review by Mao et al., which elegantly integrates mechanistic insights across the gut–brain, gut–adipose, and gut–pancreas axes, and we propose three extensions to strengthen its clinical relevance. First, I highlight the bidirectional interplay between GLP‐1 receptor agonists (GLP‐1 RAs)—now first‐line obesity pharmacotherapy—and the gut microbiome: GLP‐1 RAs enrich Akkermansia muciniphila and short‐chain‐fatty‐acid‐producing taxa, while baseline microbiome composition modulates individual drug responsiveness. Second, I argue for greater attention to upper gastrointestinal microbial niches and synthetic biology approaches, including engineered Clostridium butyricum strains that secrete GLP‐1 locally within the intestinal lumen. Third, I emphasize the circadian dimension of the gut–endocrine axis—time‐restricted feeding restores microbial diurnal oscillations—and its integration with phenotype‐guided precision medicine (e.g., “hungry gut,” “hungry brain,” and “emotional hunger” subtypes). Incorporating these perspectives would transform the review into a practical roadmap for personalized obesity intervention.