Abstract

Obesity is a chronic, relapsing metabolic disease in which the gut microbiota plays a central regulatory role. 
Dysbiosis, impaired barrier integrity and altered microbial metabolites contribute to increased energy harvest, 
low-grade inflammation, insulin resistance and disruption of gut–brain signaling. Conventional microbiota
directed strategies such as diet, probiotics, prebiotics, antibiotics and fecal microbiota transplantation have 
shown promise but are limited by poor specificity, variable engraftment and limited spatial and temporal control 
within the gastrointestinal tract. Nanoparticle-based delivery systems provide new opportunities to precisely 
modulate microbial communities and their metabolic outputs by protecting labile cargos, targeting specific gut 
regions and responding to local physicochemical cues. This review summarizes current understanding of 
microbiota–obesity interactions and outlines how polymeric, lipid, inorganic and hybrid nanoparticles can be 
engineered for gastrointestinal targeting. We discuss mechanistic pathways through which nano-systems 
influence microbial ecology, epithelial barrier function and host metabolic signaling, including applications in 
probiotic, prebiotic, phage, nucleic-acid and engineered-microbe therapies. Finally, we examine safety, ecological 
and regulatory challenges, and highlight future directions for integrating nanoparticle-mediated microbiota 
modulation into precision obesity management.