Probiotics and Semaglutide Therapy: Mechanistic Perspectives and Potential Interactions in Gut Microbiota, Gastrointestinal Function, and Metabolic Health

Background/Objectives: Semaglutide is one of the currently widely used medications that have shown particularly strong effects on glycemic control and body weight in people with obesity and diabetes. However, gastrointestinal adverse effects are common during semaglutide therapy. Gut microbiota and probiotic supplementation have also attracted growing interest because of their potential effects on metabolic health and gastrointestinal function and their ability to support gastrointestinal health. Methods: This narrative review article investigated the potential interaction between probiotics and semaglutide in relation to gut microbiota, gastrointestinal function, and metabolic health. Results: Patients with metabolic disorders, including type 2 diabetes and obesity, commonly have gut dysbiosis, characterized by an imbalance in the composition and function of the intestinal microbiota. Semaglutide, as a currently important treatment for metabolic disorders, provides effective glycemic control and clinically meaningful weight loss; however, gastrointestinal adverse events are among the most frequently reported adverse effects of semaglutide treatment. Modulation of the gut microbiota may contribute to improved metabolic outcomes and gastrointestinal function. Probiotics may further modulate the gut microbiota by restoring microbial homeostasis, increasing the abundance of beneficial microorganisms, and improving microbial diversity. In addition, probiotic supplementation has been associated with improved metabolic outcomes, including better glycemic control in individuals with diabetes. Conclusions: Probiotics may potentially complement the metabolic effects of semaglutide and support gastrointestinal function and gut microbiota during semaglutide therapy. However, further studies are required to determine whether a clinically meaningful interaction exists between semaglutide and probiotics.