Gut microbiota responses to two-dimensional materials: insights from in vivo models and in vitro antibacterial studies.

Two-dimensional (2D) materials are increasingly applied in environmental and biomedical fields, raising concerns about their interactions with the gut microbiota following oral exposure. In this review, we summarize current understanding of the effects of 2D materials, ranging from graphene-based materials (GBMs) to emerging 2D materials such as transition metal dichalcogenides (TMDs) and transition metal carbides and nitrides (MXenes), on the gut microbiota and the associated biological outcomes. We first summarize in vivo studies, mainly using mouse and zebrafish models and focusing on GBMs, demonstrating that 2D materials exposure can induce gut microbiota dysbiosis, often in association with local and systemic host responses. To provide mechanistic insights, we further examine how key physicochemical properties, particularly nanosheet dimensions, surface chemistry, and material transformation, determine the interactions between 2D materials and bacterial cells, drawing from the extensive body of in vitro antibacterial research. Finally, we highlight future research directions beyond the need for more efforts on emerging 2D materials, including linking physicochemical properties of 2D materials to microbial responses in vivo and analyzing the temporal response patterns of the gut microbiota. We also emphasize the development of community-relevant in vitro models and the need to dissect the potential biotransformation of 2D materials by the gut microbiota. A deeper understanding of the interactions between 2D materials and the gut microbiota will not only advance the safety assessment of these materials but also foster the development of safer-by-design 2D materials.