Co-exposure to a high-fat diet and nanoplastics synergistically exacerbates intestinal microbiota dysbiosis and susceptibility

In real life, humans will continue to be affected by the combined influence of environmental pollutants and specific dietary patterns for a long period of time. An unbalanced diet structure may increase human susceptibility to the toxicity of environmental pollutants. This study indicates that under a high-fat diet, exposure to PS NPs will further exacerbate the disorder of the intestinal flora structure and function. The main manifestations include reduced diversity, simplified community structure, and enrichment of mobile genetic elements. This ultimately led to the evolution of the intestinal microbial ecosystem towards a simpler structure and reduced genetic stability. At the molecular mechanism level, the combination of a high-fat diet and PS NPs leads to impaired intestinal barrier function (inhibition of Occludin and Muc2 expression), decreased mucosal immune defense capacity (disorder in Reg3a/Reg3b expression), and exacerbation of the imbalance between pro-inflammatory and anti-inflammatory factors (TNF-α and IL-6 levels increased, and the IL-10 level decreased). These results collectively indicate that under high-fat diet conditions, the composite PS NPs will further exacerbate the disruption of the intestinal barrier structure, suppress the mucosal defense ability, and intensify the inflammatory response. This discovery highlights that the intestinal flora disorder caused by a high-fat diet lays the foundation for intestinal susceptibility formation. A high-fat diet may significantly reduce the intestinal defense against environmental pollutants, resulting in higher health risks for individuals consuming a high-fat diet at the same level of PS NP exposure.