Nanomaterial journey in the gut: from intestinal mucosal interaction to systemic transport

Engineered nanomaterials (NMs) are commonly utilized in food additives, cosmetics, and therapeutic applications due to their advantageous properties. Consequently, humans are frequently exposed to exogenous nanomaterials through oral ingestion, thus making the intestinal mucosal system a primary site for these particles. Understanding the interactions between nanomaterials and the intestinal mucosal system is crucial for harnessing their therapeutic potential and mitigating potential health risks from unintended exposure. This review aims to elucidate recent advancements in the dual effects of nanomaterials on the intestinal mucosal system. Upon entering the gut lumen, nanomaterials will interact with diverse intestinal components, including trillions of gut microbiota, mucus layer, intestinal epithelial cells (IECs), and the intestinal immune system. Additionally, the systemic fate and transportation of nanomaterials to distal organs, such as central nervous system, are also highlighted. These interactions result in a distinct biological effect of nanomaterials on the multilayer structure of intestine, thus displaying complex journeys and outcomes of nanomaterials in the living body. This in-depth exploration of the in vivo destiny and immunological implications of nanomaterials encountering the intestine has the potential to propel advancements in oral drug delivery techniques and motivate future investigations in novel toxicology research. Nanomaterials interact with the gut microbiome, mucus layer, and epithelial cells, influencing immune responses and facilitating transport to distant organs via blood, lymphatic, and neural pathways, impacting intestinal and systemic health.