Early life stress is increasingly recognized as a critical factor shaping neural development and long-term sensory processing. It is also a well-established driver of visceral dysfunction and central to the pathogenesis of irritable bowel syndrome (IBS). While gastrointestinal and psychological consequences are well documented, its impact on auditory function remains unclear. Here, we employed neonatal colorectal distension in Sprague-Dawley rats to model early life visceral stress and IBS. At 7 weeks, rats exhibited pronounced visceral and somatic hypersensitivity, validated by abdominal withdrawal reflex scores and von Frey testing. Auditory brainstem responses (ABR) revealed markedly shortened wave latencies and increased amplitudes across click and tone stimuli despite normal thresholds, indicating auditory pathway hyperexcitability ( P < 0.001). Cochlear proteomic profiling identified 219 differentially expressed proteins enriched in vesicle trafficking, synaptic signaling, and inflammatory pathways, including MAPK, PI3K-Akt, and TNF signaling. Network analyses highlighted transcriptional, proteasomal, and mitochondrial alterations as potential molecular drivers. Together, these findings provide the first evidence that early life visceral stress not only programs persistent gastrointestinal hypersensitivity but also sensitizes auditory processing via cochlear molecular changes. This work extends the developmental psychobiology framework by linking early life adversity to cross-modal sensory dysfunction and highlights a novel gut–inner ear axis. • Early life visceral stress induces auditory hypersensitivity in rats in early adulthood. • Auditory brainstem responses show shortened latencies and increased amplitudes. • Cochlear proteomics reveals alterations in vesicle trafficking and inflammation. • Stress-induced molecular remodeling suggests mechanisms of auditory sensitization.
Zhang et al. (Wed,) studied this question.