Proton pump inhibitors (PPIs) are among the most widely used drugs in clinical practice. Although generally effective and well tolerated, their widespread and frequently prolonged use has raised concerns about both gastrointestinal and systemic adverse effects. Some of these effects may be directly or indirectly mediated by proton-pump-inhibitor-induced alterations of the gut microbiota. Proton pump inhibitors can reshape gastrointestinal microbial communities through multiple mechanisms, including gastric acid suppression, impaired barrier function, and modulation of the immune and metabolic pathways. The resulting dysbiosis promotes oral-to-gut microbial translocation, reduces microbial diversity, and favors the expansion of potentially pathogenic taxa. These alterations have been associated with several gastrointestinal disorders such as small intestinal bacterial overgrowth, enteric infections, and disturbances of the gut–liver axis, while emerging evidence suggests broader implications for carcinogenesis and the response to immune checkpoint inhibitors. In this context, microbiota-modulating interventions, including probiotics, may provide clinical benefits; however, the current evidence remains limited and inconsistent, precluding their routine use. By integrating mechanistic and clinical evidence, this review aims to clarify the role of the gut microbiota in proton-pump-inhibitor-related adverse effects and to assess the potential of microbiota-targeted strategies to mitigate their clinical consequences.

Early rectal cancer represents a challenging setting in which accurate locoregional staging is essential to guide appropriate treatment. Current diagnostic strategies primarily include magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, both modalities show significant limitations in early-stage disease, particularly in T staging. This diagnostic gap impacts therapeutic decision-making, particularly in patients with lesions suggestive of deep submucosal invasion. In these cases, endoscopic submucosal dissection (ESD) may be insufficient to achieve adequate vertical negative margins, whereas radical surgery is associated with considerable morbidity and potential impairment of quality of life. In this gray zone, endoscopic intermuscular dissection (EID) has recently emerged as a novel therapeutic approach designed to overcome the limitations of standard endoscopic resection. By enabling dissection within the deeper intermuscular plane, it can achieve curative resections while preserving rectal wall integrity. This narrative review aims to explore the current diagnostic gaps in early rectal cancer and to define the potential role of EID within the current therapeutic algorithm.