Reconceptualizing negative endoscopy as a positive contextual indicator for disorders of gut-brain interaction

In the contemporary landscape of gastroenterology, the “negative” endoscopy—an examination revealing no gross structural, mucosal, or biochemical abnormalities—is frequently perceived by both clinicians and patients as a diagnostic non-event, a failure to identify a cause, or an ambiguous dead-end. This perspective paper argues for a fundamental epistemological and clinical paradigm shift: a negative endoscopic result, when combined with appropriate biopsy protocols and clinical history, should not be classified merely as the absence of organic disease but as positive, corroborative evidence acting as a contextual indicator supporting a diagnosis of a Disorder of Gut-Brain Interaction (DGBI). By integrating the verified absence of macroscopic “hardware” damage (structural pathology) with the presence of characteristic symptom patterns, clinicians can support the diagnosis of a “software” malfunction (visceral hypersensitivity and altered central processing). This report provides a detailed analysis of the physiological mechanisms of the brain-gut axis that underpin this argument, dissects the psychological impact of diagnostic labeling versus invalidation, and proposes a comprehensive novel clinical workflow—the “Affirm-Explain-Transform” (AET) model—to convert the negative endoscopy from a source of clinical ambiguity into a potent therapeutic tool.