Stefan-Lucian Popa

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/Objectives: Obesity is increasingly recognised as a clinically relevant comorbidity in patients with inflammatory bowel disease (IBD), with potential effects on inflammatory burden, treatment response, surgical risk, nutritional status, and quality of life. Endoscopic bariatric therapies (EBTs), including intragastric balloons and endoscopic sleeve gastroplasty, offer minimally invasive weight-loss options between pharmacotherapy and bariatric surgery. However, their role in IBD remains poorly defined. This narrative review examines patient selection, nutritional risk, periprocedural management, and future research priorities for EBTs in IBD. Methods: A narrative review was performed, focusing on obesity in IBD, bariatric endoscopy, bariatric surgery, nutritional deficiencies, sarcopenic obesity, biologic therapy, and periprocedural risk. Evidence from general bariatric endoscopy studies, IBD-specific obesity literature, clinical guidelines, and expert consensus documents was synthesised. Results: Direct evidence evaluating EBTs in patients with IBD is very limited. Most practical considerations must therefore be extrapolated from general bariatric endoscopy studies and bariatric surgery data in IBD. Patients with sustained clinical and preferably endoscopic remission, stable nutritional status, and uncomplicated disease phenotypes may represent the most suitable candidates. Active upper gastrointestinal Crohn’s disease, stricturing or penetrating disease, recent surgery, severe malnutrition, sarcopenia, and high-dose corticosteroid exposure should prompt caution or avoidance. Structured follow-up is needed to monitor nutritional deficiencies, body composition, procedural symptoms, and possible IBD activity. Conclusions: EBTs may represent a promising option for selected patients with IBD and obesity, but current evidence remains insufficient for firm recommendations. Prospective registries, phenotype-stratified cohort studies, and comparative trials are needed.

Background and Aims: Inflammatory bowel disease (IBD) requires reliable non-invasive biomarkers to monitor mucosal healing, systemic inflammation, and gut-liver axis involvement. This study evaluated the diagnostic potential of accessible clinical parameters, including fecal calprotectin (FC), hemogram-derived ratios, and composite albumin-integrating and liver fibrosis scores, alongside standardized endoscopic severity findings. Methods: This retrospective observational study included 36 adult IBD patients [21 with Crohn’s disease (CD), 15 with ulcerative colitis (UC) receiving biological therapy. Systemic inflammatory indices [e.g., neutrophil-lymphocyte ratio (NLR)], nutritional scores [e.g. prognostic nutritional index (PNI)], and hepatic fibrosis scores [e.g. aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 (FIB-4), platelet-albumin-bilirubin (PALBI)] were assessed. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance, reported as area under the curve (AUC), of these biomarkers. Results: Routine laboratory parameters and non-invasive liver fibrosis indices showed no statistically significant differences between CD and UC patients. Biologic treatment initiation differed significantly between the groups (p<0.001). Endoscopically, CD presented marked phenotypic heterogeneity with predominantly ileocolonic involvement, whereas active UC was characterized mainly by pancolitis. Fecal calprotectin concentrations were notably higher in UC (median 1000 μg/g) compared to CD (310 μg/g). Diagnostically, FC demonstrated the highest predictive capacity for differentiating the conditions (AUC=0.74). Furthermore, albumin-integrating scores, specifically the PALBI score (AUC = 0.686) and PNI (AUC = 0.657), alongside NLR (AUC=0.632), outperformed traditional hepatic indices in capturing the systemic inflammatory toll. Complex composite inflammatory formulas unexpectedly underperformed. Conclusions: FC remains the most robust non-invasive marker for localized mucosal inflammation. Albumin-integrating scores and simple hemogram-derived ratios better reflect the systemic inflammatory burden than pure hepatic fibrosis indices, but their moderate diagnostic accuracies preclude independent clinical application. Effective IBD management requires integrating these non-invasive adjunctive tools with standard endoscopic assessments within a personalized, multiparametric framework.

Background and Aims: Antispasmodics and antidepressants are standard therapies for managing both the gastrointestinal symptoms and psychological comorbidities associated with irritable bowel syndrome (IBS). However, direct comparative evidence regarding their efficacy across different symptom domains is scarce. This systematic review and network meta-analysis aimed to assess the relative effectiveness of these agents on abdominal pain, psychological outcomes, overall IBS symptom severity, and quality of life (QoL). Methods: We conducted a comprehensive search of PubMed, EMBASE, and Scopus to identify relevant randomized controlled trials evaluating antispasmodics and antidepressants for IBS. Eligible studies underwent quality assessment and were synthesized using network meta-analysis. We calculated standardized mean differences (SMDs) with 95% confidence intervals (CIs) for pain outcomes (VAS), anxiety, depression, the IBS Severity Scoring System (IBS-SSS), and QoL. Results: Twenty-nine studies were included in the analysis. Significant reductions in pain (VAS) were observed with imipramine (SMD -34.06; 95%CI -51.89 to -16.22) and the alverine/simethicone combination (SMD -6.23; 95%CI -9.93 to -2.53), while mebeverine and anise oil showed benefits in specific IBS subgroups. The most substantial improvements in anxiety occurred with flupentixol–melitracen (SMD -6.63; 95%CI -10.13 to -3.13), followed by small-intestinal release peppermint oil, fluoxetine, and vortioxetine. Imipramine was most effective for depressive symptoms (SMD -9.40; 95%CI -10.29 to -8.51), followed by venlafaxine, flupentixol–melitracen, desipramine, and vortioxetine. Amitriptyline was the only agent to show significant improvement in IBS-SSS scores (SMD -23.70; 95%CI -43.27 to -4.13). The largest gains in QoL were associated with otilonium bromide (SMD 30.90; 95%CI 26.62 to 35.18), followed by venlafaxine, amitriptyline, and cumin sofouf. Conclusions: Imipramine and alverine/simethicone were superior for reducing abdominal pain, whereas flupentixol–melitracen, peppermint oil, fluoxetine, and vortioxetine demonstrated the strongest anxiolytic effects. Effective options for depression included imipramine, venlafaxine, flupentixol–melitracen, desipramine, and vortioxetine. Notably, amitriptyline uniquely improved overall IBS severity scores, while otilonium bromide, venlafaxine, amitriptyline, and cumin sofouf provided the greatest benefits for QoL. These findings clarify comparative efficacy and may guide tailored pharmacotherapy strategies for IBS patients.

Hepatocellular carcinoma (HCC) is undergoing a profound global epidemiological shift, transitioning from viral-driven etiologies to metabolic dysfunction-associated steatotic liver disease (MASLD). This transition challenges traditional cirrhosis-centric surveillance, as a significant proportion of MASLD-HCC develops in non-cirrhotic livers. Parallel to these metabolic shifts, the gut-liver axis has emerged as a central orchestrator of hepatocarcinogenesis. This review decodes the complex gut-driven pathways fueling HCC, highlighting the oncogenic consequences of structural and functional dysbiosis. Dietary patterns and etiology-specific microbial shifts compromise the intestinal and gut-vascular barriers, precipitating a structural “leaky gut”. This disruption facilitates the robust translocation of pathogen-associated molecular patterns (PAMPs), particularly lipopolysaccharide (LPS), and toxic microbial metabolites like secondary bile acids, specifically deoxycholic acid, into the portal circulation. Consequently, hepatic innate immunity is chronically activated via Toll-like receptor 4 (TLR4) signaling on Kupffer and hepatic stellate cells, fostering metainflammation, cellular senescence, genomic instability, and a highly immunosuppressive, pro-tumorigenic microenvironment. Furthermore, the depletion of keystone commensals diminishes the protective reservoir of short-chain fatty acids (SCFAs), exacerbating oncogene activation. Translating these mechanistic insights into the clinic, we explore the utility of distinct microbial signatures and metabolomic profiles as non-invasive diagnostic biomarkers. Such tools are urgently needed to bridge the early-detection gap in the expanding MASLD demographic. Finally, we discuss the pivotal role of the microbiome in modulating responses to immune checkpoint inhibitors (ICIs), notably through immune-stimulating taxa like Akkermansia muciniphila , and outline emerging gut-targeted therapies, including next-generation probiotics and fecal microbiota transplantation, aimed at restoring host-microbiome homeostasis to prevent and manage HCC. By decoding these gut-driven pathways, this review provides a comprehensive framework for integrating the microbiome-onco axis into precision oncology, offering novel avenues to combat the rising global burden of hepatocellular carcinoma.

Background and Aims: The etiology of achalasia remains incompletely understood. Accumulating evidence suggests that genetic susceptibility contributes to disease development, interacting with immune-mediated and environmental factors. This systematic review aims to comprehensively evaluate current evidence on the genetic background of achalasia, summarizing data from candidate gene studies, genome-wide association analyses, and investigations of syndromic forms of the disease. Methods: A systematic literature review was conducted to identify studies examining genetic associations, familial aggregation, syndromic achalasia, and genomic or transcriptomic alterations in patients with achalasia. Evidence was synthesized to assess genetic susceptibility factors and mechanistic pathways contributing to disease pathogenesis. Results: A total of 21 studies were included in this systematic review. The available data indicate that achalasia has a multifactorial genetic background involving HLA-related immune susceptibility, polymorphisms in immune regulatory genes, altered neurotransmission pathways, and transcriptional dysregulation. Conclusions: Genetic factors implicated in achalasia primarily involve immune susceptibility, disrupted neurotransmission, and transcriptional dysregulation, collectively supporting an immune-mediated neurodegenerative mechanism underlying disease pathogenesis. Integrating data from idiopathic and syndromic achalasia with genomic approaches may improve understanding of disease mechanisms and enable earlier diagnosis and personalized therapeutic strategies.

Background and Aims: Early identification by gastroenterologists of peritonitis in acute appendicitis may support timely decision-making when clinical assessment and imaging are equivocal. The aim of this study was to assess the diagnostic and predictive value of routinely available laboratory parameters and systemic inflammatory indices in identifying peritonitis among patients undergoing surgery for acute appendicitis. By integrating clinical features, biochemical markers and composite hematological ratios, this study seeks to contribute to improved risk stratification and early decision-making in patients with acute appendicitis. Methods: We conducted a single-center retrospective observational study of adults (≥18 years) undergoing appendectomy for acute appendicitis (July 2023–July 2024). Patients were stratified by intraoperatively confirmed peritonitis. Admission biomarkers and complete hemogram–derived indices were evaluated using ROC analysis (AUC; Youden cut-offs). Multivariable logistic regression models were adjusted for age, gender, time from symptom onset to surgery, and Alvarado score. Results: Among the 99 patients included, 52 (52.5%) had peritonitis. Compared with patients without peritonitis, those with peritonitis had a higher median age, body mass index (BMI), Alvarado score, and C-reactive protein (CRP) level. CRP showed the highest discriminatory ability for identifying peritonitis (AUC=0.713, 95%CI: 0.613–0.813), with a cut-off value of 15.1 mg/L, corresponding to a sensitivity of 70.6% and a specificity of 70%. Hemogram-derived inflammatory indices demonstrated moderate discriminatory performance for predicting peritonitis, including the monocyte-to-lymphocyte ratio (MLR; AUC=0.680; cut-off ≥0.653), eosinophil count (AUC=0.663; cut-off 0.035×10⁹/L) for predicting the absence of peritonitis, the systemic inflammation response index (SIRI; AUC=0.657; cut-off ≥7.42), and the neutrophil-to-lymphocyte ratio (NLR; AUC=0.647; cut-off ≥10.855). In adjusted models, MLR ≥0.653 (aOR=6.92, 95%CI: 2.55–21.21), SIRI ≥7.42 (aOR=6.89, 95%CI: 2.46–22.29), and NLR ≥10.855 (aOR=5.88, 95%CI: 2.16–18.13) were associated with increased odds of peritonitis, whereas eosinophil count ≥0.035×10⁹/L was inversely associated with peritonitis (aOR=0.22, 95%CI: 0.08–0.54). Conclusions: Hemogram-derived inflammation indices, particularly MLR, SIRI, and NLR, are independently associated with intraoperative peritonitis and may complement CRP for preoperative risk stratification. Prospective multicenter validation is warranted to confirm thresholds and clinical utility.

Artificial intelligence (AI) has rapidly expanded across gastroenterology, enabling advances in real-time endoscopic detection, radiologic interpretation, digital pathology, multimodal prognostication, and electronic health record–based decision support. Despite strong performance in controlled studies and increasing regulatory adoption, the clinical integration of AI remains challenged by limitations that threaten reliability, safety, and equitable deployment. This editorial synthesizes the major sources of vulnerability across current AI applications in gastroenterology, including dataset bias, limited generalizability, annotation variability, underrepresentation of rare lesions, and performance degradation in real-world environments. Endoscopic AI systems—the most mature applications—face persistent false positives, false negatives, alert fatigue, and operator deskilling, while most algorithms lack explainability and fail to incorporate essential clinical context. Predictive models based on EHR or imaging data are hindered by data noise, evolving clinical practices, and susceptibility to model drift. Additional risks arise from automation bias, suboptimal workflow integration, and unresolved ethical, regulatory, and liability considerations. Ensuring safe and meaningful clinical deployment requires continuous post-deployment monitoring, rigorous external validation, improved interpretability, and the development of multimodal systems that integrate imaging with clinical and biological data. Equally critical is clinician education to preserve human oversight and prevent overreliance on algorithmic output. By recognizing and addressing these limitations, the field can move beyond accuracy-focused evaluation toward designing AI systems that are robust, transparent, and capable of improving patient-centered outcomes in diverse real-world settings.