Ahmed Abdelghafar

The intricate interplay between the gut microbiome and the enteric nervous system remains a paramount focus in understanding the multifactorial pathogenesis of disorders of gut–brain interaction (DGBI), most notably irritable bowel syndrome (IBS). While the clinical entity of post-infectious IBS is well-established, the independent, long-term pathophysiological impact of iatrogenic antibiotic exposure is garnering critical attention within neurogastroenterology. This narrative review provides a comprehensive synthesis of current epidemiological and mechanistic evidence positioning antibiotic-induced microbial depletion as a potential predisposing factor for incident IBS. By evaluating recent literature, we highlight epidemiological trends demonstrating a consistent, dose-dependent relationship between cumulative antibiotic courses, particularly broad-spectrum agents, and an elevated risk of developing IBS, independent of prior acute enteric infections. Furthermore, we explore the mechanistic underpinnings of this association, focusing on how systemic antibiotics induce persistent, detrimental alterations in commensal diversity. This resulting dysbiosis initiates a proposed cascade of downstream consequences, including compromised epithelial barrier integrity, persistent low-grade mucosal inflammation, and altered bile acid metabolism. These localized disruptions serve as established triggers for visceral hypersensitivity and dysregulated gastrointestinal motility communicated via the gut–brain axis. Ultimately, this review underscores that antibiotic exposure may act as a significant, modifiable risk factor for IBS pathogenesis. Recognizing this substantial iatrogenic risk reinforces an urgent clinical imperative for stringent antimicrobial stewardship and emphasizes the necessity for future research directed toward prophylactic, microbiome-sparing strategies to mitigate the escalating global burden of DGBIs.

Background and Objectives: Procalcitonin (PCT) is widely used to support the diagnosis of bacterial infection and sepsis, yet clinically relevant elevations also occur in multiple non-infectious conditions. This systematic review aimed to synthesize human evidence on non-infectious causes of elevated PCT and to summarize proposed pathophysiological mechanisms, with the goal of supporting context-based interpretation in clinical practice. Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was performed from inception to 31 July 2025. Human studies published in English reporting quantitative PCT values in non-infectious contexts were eligible (observational studies, clinical trials, and case series with ≥5 patients). Results: Seventy-six unique studies were included. Evidence was organized across systemic inflammatory responses, cardiovascular pathology, nephrological disorders and renal replacement therapy, pulmonary diseases, gastrointestinal and hepatopancreatic diseases, autoimmune and rheumatologic conditions, neurologic and ophthalmologic conditions, onco-hematologic disorders, surgery, traumatology and transplanted patients. Across conditions, non-infectious PCT elevations were variable and frequently overlapped with ranges reported in bacterial infection, particularly in settings characterized by severe sterile inflammation and tissue injury (e.g., major surgery, trauma, shock, pancreatitis, and burns), as well as in selected malignancies with tumor-associated PCT production. Conclusions: Elevated PCT is not synonymous with bacterial infection. Interpretation should emphasize clinical context, timing, and serial trends rather than isolated thresholds, especially in high-acuity settings with strong non-infectious inflammatory stimuli. Standardized reporting of assays and sampling time points and condition-specific kinetic data are needed to refine diagnostic and stewardship algorithms.