The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect^® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to −33%). In contrast, low concentrations of PPRO (50–100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux.

Neuroglobin (NGB), initially identified for its oxygen-binding capacity in neuronal tissues, has emerged as a multifunctional protein involved in neuroprotection, oxidative stress regulation, and mitochondrial homeostasis. Although its functions have been extensively studied in the central nervous system (CNS), its potential role in the gut–brain axis (GBA) remains largely unexplored. The GBA integrates neural, endocrine, immune, and metabolic signaling between the gastrointestinal tract and the brain, and growing evidence from microbiome, neurobiology, endocrinology, and nutrition research suggests that several pathways involved in GBA signaling may also influence NGB expression or activity. However, direct experimental evidence, particularly from in vivo studies, remains limited. This hypothesis-driven review integrates evidence from diverse fields to explore the possibility that NGB may represent a molecular link between gut-derived signals and neuroprotective mechanisms. We summarize current knowledge of NGB biology and discuss indirect evidence indicating that microbial metabolites, dietary phytochemicals, and hormonal mediators, including estradiol, may converge on pathways associated with NGB regulation. Based on these observations, we propose a conceptual framework in which NGB could participate in gut–brain communication while emphasizing that this hypothesis requires experimental validation. By bringing together findings that have not previously been considered within a unified context, this review highlights key knowledge gaps, opens new perspectives on the potential involvement of NGB in the GBA, and provides a foundation for future mechanistic studies in neurodegenerative and neuroinflammatory disorders.