Abstract
Potassium sorbate (PS) is a widely used antimicrobial additive employed as a preservative in food, cosmetics, and animal feed. Early childhood represents a critical developmental window characterized by rapid growth, immune system maturation, gut microbiota establishment, and physiological homeostasis development, which may be particularly vulnerable to chemical exposures (during which chemical exposures may exert heightened impacts). Nevertheless, the effects of PS on childhood development and gut microbiota remain poorly understood, and its potential trans-generational effects have yet to be elucidated. In this study, we employed Drosophila melanogaster, an established model for studying evolutionarily conserved aspects of development, metabolism, and host-microbiota interactions, to systematically evaluate PS toxicity across multiple parameters: developmental dynamics, gut microbiota composition, gene regulation in adulthood, and trans-generational effects. Our findings demonstrate a dose-dependent biphasic response: while low-dose PS exposure (25 mg/L) accelerated larval pupation and adult emergence, suggesting a potential growth-promoting effect, high-dose exposure (≥ 500 mg/L) significantly delayed development and reduced adult lifespan (observed in females at 1,000 and males at 500-1,000 mg/L). Notably, trans-generational analysis revealed persistent developmental delays in the F1 generation, with offspring of 1,000 mg/L-exposed parents showing prolonged larval pupation time despite normal adult emergence timelines, indicative of partial developmental recovery. Mechanistically, high-dose PS disrupted endocrine signaling and altered expression of key developmental pathway regulators (EcR, InR, TOR, and E74B). These transcriptional changes were largely reversible in offspring, further supporting a similar gradually wash out recovery. While gut microbiota remained stable in exposed parents, offspring of 1,000 mg/L-exposed flies had significant microbiome alterations, highlighting clear trans-generational dysbiosis. This study provides new evidence that PS exposure during a sensitive developmental period in D. melanogaster can perturb development and gut microbial homeostasis across generations, offering insights relevant to understanding how early-life chemical exposures might influence conserved biological processes in higher organisms.
