Irritable bowel syndrome with diarrhoea (IBS-D) is one of the most frequently encountered disorders of gut-brain interaction, yet its diagnosis remains challenging owing to the substantial symptom overlap with a wide range of conditions. These mimics, most notably microscopic colitis (MC), bile acid diarrhoea (BAD), small intestinal bacterial overgrowth (SIBO), coeliac disease, exocrine pancreatic insufficiency (EPI), endocrine disorders, lactase deficiency, sucrase-isomaltase deficiency, early inflammatory bowel disease (IBD) and functional diarrhoea (FD) can all present with identical clinical features, leading to diagnostic error, delayed treatment, and inappropriate symptom-based management. This narrative review synthesizes literature from 1997 to 2025, incorporating guideline recommendations (ACG, AGA, BSG, ECCO), RCTs, meta-analyses, systematic reviews, and expert consensus statements. This review highlights the most critical mistakes in diagnosing, evaluating, managing, and monitoring IBS-D and its mimics, with lapses in clinical reasoning and guideline adherence most consequential.

Background/Objectives: Ultra-high-magnification endoscopy (Endocyto) visualizes microscopic mucosal structures and has been proposed as a tool for assessing mucosal inflammation. We previously developed an endocytoscopic classification system (EC-A to EC-D) for grading the severity of inflammation. In this study, we investigated the relationship between endocytoscopic classification and microRNA (miRNA) expression in 36 patients with ulcerative colitis (UC). Methods: This cross-sectional study was conducted in two phases at two institutions. In the first phase, microarray analysis was performed on biopsy samples from patients with UC and healthy controls enrolled at Nagasaki University Hospital. In the second phase, 36 patients with UC who underwent total colonoscopy via Endocyto at Tottori University Hospital were included, and selected miRNAs were analyzed via quantitative polymerase chain reaction. Results: Differentially expressed miRNAs were identified, and four (miR-141-5p, miR-192-5p, miR-194-5p, and miR-215-5p) were downregulated in inflammatory areas. Notably, miR-192-5p expression was markedly lower in the EC-B and EC-C+D groups than in the EC-A group. Furthermore, expression of CXC motif ligand 2 (CXCL2), a pro-inflammatory chemokine, was upregulated in inflammatory tissues and negatively correlated with miR-192-5p expression. Conclusions: These results indicate that reduced miR-192-5p expression is inversely associated with CXCL2 expression and that, among the miRNAs examined, miR-192-5p downregulation most consistently corresponded to the endocytoscopic classification. Our findings suggest that Endocyto may serve as a real-time, in vivo adjunct for a histology-like assessment of mucosal inflammation; its clinical utility requires prospective validation.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease that typically presents in middle age, and reports in young adults are uncommon. Herein, we describe the case of a 22-year-old woman with ulcerative colitis who was referred for evaluation of persistent proteinuria and microscopic hematuria. Kidney biopsy showed mild mesangial hypercellularity with increased mesangial matrix on light microscopy. Electron microscopy revealed randomly oriented, nonbranching microfibrils measuring approximately 20 nm in diameter within the mesangial areas. Immunohistochemistry for DnaJ heat shock protein family member B9 (DNAJB9) was positive in the glomeruli, confirming the diagnosis of FGN. Given the unusually young onset, the clinical course, and the presence of intestinal inflammatory lesions, an autoinflammatory disorder, specifically atypical familial Mediterranean fever (FMF), was suspected. Therapy with an angiotensin II receptor blocker was initiated for proteinuria, and colchicine was subsequently added while mesalazine was tapered. After treatment, urinary protein excretion decreased, and endoscopic and histologic bowel inflammation improved. This case highlights three practical points: DNAJB9 immunostaining is useful to establish FGN when classic ultrastructural features are present, FGN can occur in young adults, prompting evaluation for underlying systemic or autoinflammatory conditions, and in patients with intestinal lesions resembling inflammatory bowel disease, consideration of FMF may lead to colchicine therapy that benefits renal and gastrointestinal manifestations.

Microscopic colitis (MC), including collagenous colitis (CC), lymphocytic colitis (LC) and incomplete MC, is a common cause of chronic watery diarrhoea. Drugs are reported triggers, but observational studies cannot establish individual causality. We reviewed case-level evidence and graded causality using dechallenge/rechallenge criteria. We included published biopsy-confirmed MC case reports and series in which drug exposure preceded symptoms and dechallenge was documented. Data were extracted at the patient level without language or date restriction. Cases were graded as Tier 1 for positive rechallenge or Tier 2 for dechallenge without rechallenge. Quality was assessed using the Murad tool. Twenty-four studies including 69 patients met criteria. Proton-pump inhibitors were most frequent (29/69, 42%), and acid suppressants plus NSAIDs accounted for 36/69 cases (52%). Other agents included ticlopidine, dopaminergic anti-Parkinson drugs, etifoxine, a venotonic, ACE inhibitors and antidepressants. CC and LC were both common. All cases were dechallenge-positive; 11 (16%) had positive rechallenge. Median reported latency was 12 days (range, 5-112). Histology normalised in 22/26 re-biopsied cases. Case-level evidence supports drug-related MC, especially with acid suppressants and NSAIDs. Drug withdrawal remains the key diagnostic and therapeutic step.

Background and Objectives: Microscopic colitis (MC) encompasses two chronic inflammatory disorders of the large intestine: collagenous colitis (CC) and lymphocytic colitis (LC). Both conditions are characterised by chronic watery diarrhoea and substantially impaired quality of life. Diagnosis relies on colonoscopy with multiple biopsies, and no reliable non-invasive biomarker currently exists. This exploratory study aimed to investigate circulating fatty acid-binding protein 2 (FABP2), interleukin-10 (IL-10), and lipopolysaccharides (LPSs) as potential biomarkers for MC and to compare their profiles with those in ulcerative colitis (UC). Materials and Methods: Plasma samples were obtained from 45 patients with active CC, 16 patients with active LC, 52 healthy controls, 43 patients with active UC, and 43 patients with inactive UC. Concentrations of FABP2, IL-10, and LPS were measured by enzyme-linked immunosorbent assay (ELISA). Results: Plasma FABP2 concentrations differed significantly across groups (Kruskal-Wallis p = 0.008). CC patients exhibited the highest levels (median 1719.0 pg/mL, IQR 1364.0-2240.0) compared with active UC (median 1272.0 pg/mL, IQR 861.7-1727.5; p = 0.005) and inactive UC (median 1334.0 pg/mL, IQR 854.2-1702.0; p = 0.001), but did not differ significantly from controls (median 1364.5 pg/mL, IQR 982.6-2160.5; p = 0.076) or LC (median 1421.5 pg/mL, IQR 1207.0-2002.2; p = 0.171). IL-10 concentrations also differed across groups (Kruskal-Wallis p = 0.029 after removal of one extreme outlier in active UC). Active UC patients had significantly lower levels (median 2.6 pg/mL, IQR 1.4-4.6) than CC (median 4.0 pg/mL, IQR 3.0-7.2; p = 0.009) and controls (median 4.8 pg/mL, IQR 2.6-7.4; p = 0.005). LPS concentrations showed no overall differences across groups (Kruskal-Wallis p = 0.55), although CC patients had numerically higher levels (median 73.7 pg/mL, IQR 45.6-104.9) compared with controls (median 56.4 pg/mL, IQR 33.7-87.1; p = 0.124). No significant differences were observed between LC and other groups for any biomarker. Conclusions: In this exploratory study, plasma FABP2 and IL-10 showed limited diagnostic accuracy in differentiating CC from UC but failed to distinguish MC from healthy controls. LPS levels were not significantly different among study groups. None of the biomarkers reliably separated LC from other groups, possibly reflecting the small LC sample size. These preliminary findings suggest subtle differences in circulating biomarker profiles between CC and UC that warrant validation in larger cohorts.

BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease associated with oxidative stress and inflammation. Natural products may offer protective effects, though their mechanisms remain unclear. Hawthorn fruit (Crataegus monogyna) is known for its antioxidant and anti-inflammatory properties, providing a rationale to explore its potential against UC ObjectiveTo evaluate the protective effects and mechanisms of Crataegus monogyna fruit extract (CMFE) in acetic acid-induced UC in rats. MethodsSix groups of Wistar rats were used: control, acetic acid (AA), AA + CMFE (100, 200, 400 mg/kg, p.o.), and AA + sulfasalazine (100 mg/kg, p.o.). Treatments lasted 10 days, followed by AA rectal infusion (300 mg/kg). Colonic damage was assessed macroscopically and histologically. Oxidative stress markers (MDA, thiols, SOD, CAT, GPx) were measured in colon homogenates, while CRP, ALP, iron, and calcium levels were determined in plasma. ResultsCMFE pretreatment significantly reduced macroscopic and microscopic damage, protecting the colonic mucosa from AA-induced lesions. AA increased MDA and decreased SH-group as well as antioxidant enzyme activities, whereas CMFE restored these parameters. CMFE also normalized CRP, ALP, iron, and calcium levels, counteracting AA-induced inflammatory and metabolic disturbances. ConclusionCMFE shows strong protective effects against AA-induced colitis by modulating oxidative stress and inflammation. These findings support its potential use in green medicine as a natural therapeutic agent for inflammatory bowel diseases.

Bismuth subsalicylate is a widely available over-the-counter medication commonly used for gastrointestinal symptoms. Although generally considered safe, prolonged use can result in systemic toxicity, including severe neurological manifestations that are often underrecognized. We report the case of a 77-year-old man with microscopic colitis, lymphocytic subtype, who developed progressive encephalopathy, proximal muscle weakness, tremor, and gait instability after more than two years of daily bismuth subsalicylate use. His clinical course was marked by fluctuating neurological symptoms, multiple hospitalizations, extensive negative diagnostic evaluations, and an initial misdiagnosis of a Parkinsonian disorder. Serum testing ultimately revealed markedly elevated bismuth levels. Discontinuation of bismuth subsalicylate and supportive care resulted in gradual clinical improvement, with normalization of serum bismuth levels and gradual neurological recovery over several months. This case highlights the diagnostic challenges associated with bismuth-induced neurotoxicity and underscores the importance of thorough medication reconciliation, including over-the-counter agents. Increased clinician awareness is critical, as prompt recognition and discontinuation of bismuth-containing products can lead to substantial neurological recovery and prevent unnecessary diagnostic interventions.