Targeted Modulation of the Gut Microbiota in Obesity: From Dietary Interventions to Bacteriophage-Based Precision Therapies

Obesity is a complex chronic disease associated with metabolic and inflammatory alterations in which the gut microbiota has emerged as an important contributing factor. Obesity-associated gut dysbiosis involves not only changes in microbial composition but also alterations in microbial functions and metabolites that may affect intestinal barrier integrity, immune regulation, adipose tissue metabolism, insulin sensitivity, and glucose homeostasis. Current microbiota-modulating strategies, including dietary interventions, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, can influence the gut microbial ecosystem; however, their effects are often highly variable among individuals and generally lack the specificity required to selectively target disease-associated bacterial populations. These limitations have increased interest in precision microbiota modulation, which aims to selectively modify microbial populations, functions, or products while minimizing unnecessary alterations to the remaining microbial community. In this context, bacteriophages represent a promising biological tool because of their ability to specifically target bacterial hosts, offering the possibility of selectively reducing bacterial populations associated with obesity-related metabolic and inflammatory disturbances. Experimental studies and early human trials have shown that bacteriophage-based interventions can modulate gut microbial communities and influence inflammatory responses, supporting their potential relevance to obesity-associated chronic low-grade inflammation. However, no published clinical trials specifically evaluating targeted bacteriophage therapy for obesity treatment were identified, and its efficacy for obesity management remains unestablished. Further research is needed to identify and validate bacterial targets, optimize phage selection and cocktail design, and evaluate phage stability, bacterial resistance, immunomodulatory effects, safety, and host–microbiota interactions before clinical translation can be considered.