Engineering Strategies to Modulate the Gut Microbiome and Immune System

Abstract

The gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral delivery systems for modulating the gut microbiome. These strategies include genetic engineering of probiotics, probiotic-biomaterial hybrids, dietary fibers, and oral delivery systems for microbial metabolites, antimicrobial peptides, RNA, and antibiotics. Engineered oral formulations have demonstrated promising outcomes in reshaping the gut microbiome and influencing immune responses in preclinical studies. By leveraging these approaches, the interplay between the gut microbiota and the immune system can be harnessed for the development of novel therapeutics against cancer, autoimmune disorders, and allergies.

Figure 1.

Recent advances in engineered oral formulations for modulating the gut microbiome and immune system. Various oral formulations, including probiotic-biomaterial hybrids (100), metabolite-polymer micelles (72), self-assembled peptides (90), RNA delivery nanoparticles (94), and dietary fiber gel (49), have been developed to restore the intestinal barrier, microbial community structure, and microbial-derived metabolites. These approaches can influence the activation or differentiatioÍn of antigen-presenting cells, CD4⁺ T cells, or CD8⁺ T cells, redirect the secretion of inflammatory or anti-inflammatory cytokines, and exert therapeutic efficacy in various pathologies. Drawing was created with BioRender.com with some images adapted with permission from ref. , , and .