Strongyloides stercoralis is a soil-transmitted helminth that is increasingly reported in dogs across Europe. While most infections are subclinical, hyperinfection syndrome, marked by excessive larval proliferation and systemic spread, can occur in immunocompromised hosts. An 11-year-old male Boston Terrier dog, originating from southern France with a history of chronic diarrhoea and recent splenectomy was presented with severe regenerative anaemia, thrombocytopenia, and a degenerative left shift. Haemotropic Mycoplasma haemocanis infection was diagnosed, and doxycycline therapy was initiated. During hospitalisation, the dog developed dyspnoea, pneumonia, and progressive pleural effusion containing motile nematode larvae. Strongyloides stercoralis infection was diagnosed by morphological identification of larvae in pleural effusion (third-stage larvae) and faeces (first- and third-stage larvae) and confirmed by PCR targeting mitochondrial cox1 and nuclear 18S rDNA hypervariable regions (HVR) I and IV), followed by sequencing, which revealed the haplotypes HP16 (cox1), VI (HVR-I) and A (HVR-IV). The HVR-IV haplotype A is found in both dogs and humans, characterizing the zoonotic population of S. stercoralis. Respiratory signs worsened despite combined fenbendazole and escalating ivermectin treatment, requiring euthanasia. Post-mortem examination revealed chronic granulomatous pneumonia, a pulmonary carcinomatous nodule, lymphoplasmacytic enterocolitis, and glomerulonephritis. This case represents the first report of S. stercoralis hyperinfection in an adult splenectomised dog. It highlights the importance of including strongyloidiasis in differential diagnoses of dogs with respiratory and gastrointestinal signs, particularly in animals with compromised immunity or relevant travel history.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare non-Hodgkin lymphoma originating from mature T lymphocytes within the intestinal epithelium. It is a distinctly heterogeneous malignant tumor with a highly aggressive nature and poor prognosis. Nontuberculous mycobacteria (NTM) are ubiquitous and can infect immunocompromised hosts. NTM infections pose an increased risk of morbidity and mortality in patients with hematological malignancies, with a reported prevalence of 1.4% in those with lymphoma. Here we present a case of a 47-year-old patient, who experienced diarrhea for 8 months. Initially, the condition was misdiagnosed as intestinal tuberculosis. However, it was later correctly diagnosed as MEITL combined with NTM infection through intestinal histopathological biopsy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of the sputum. To our knowledge, it is the first documented instance of MEITL combined with NTM infection. This case serves as a reminder that NTM infection is one of the potential infectious complications in patients with MEITL.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus characterized by dysphagia and food impaction. Although uncommon, spontaneous esophageal perforation may occur, most frequently involving the distal esophagus and the gastroesophageal junction. These perforations are typically managed with surgical or endoscopic interventions. Early diagnosis and prompt initiation of treatment within the first 24 hours significantly reduce morbidity and mortality. The aim of this report is to demonstrate that gastroesophageal junction perforation secondary to eosinophilic esophagitis can be successfully managed conservatively, even in delayed presentations, and to contribute to the understanding of treatment strategies for this rare but potentially life-threatening complication. We report the case of a 35-year-old male with a 12-year history of EoE who presented to the emergency department with retrosternal pain, dyspnea, and hematemesis. Five days prior to presentation, he developed a sore throat and cherry-colored diarrhea after consuming grilled chicken and self-administered ibuprofen for symptom relief. Contrast-enhanced imaging and upper endoscopy revealed a perforation at the gastroesophageal junction. Due to the location of the lesion, endoscopic stenting or clipping was considered inappropriate. In the absence of signs of acute abdomen, mediastinitis, or significant fluid collection, a conservative management strategy was adopted. The patient was admitted to the intensive care unit and initially treated with intravenous ceftriaxone (2 g/day) and metronidazole (1.5 g/day), which were later changed to piperacillin-tazobactam (4.5 g every 6 hours) following infectious disease consultation. The patient remained clinically stable, and oral intake was initiated on day 6. Antibiotic therapy was discontinued on day 10, and the patient was discharged without complications. At the three-month follow-up, the patient reported recurrent and progressively worsening dysphagia. Control endoscopy performed at the previously visited center revealed a distal esophageal stricture preventing passage of the gastroscope; therefore, a 12-cm fully covered self-expandable esophageal stent was placed. The stent was removed 20 days later, and the patient remained asymptomatic during the subsequent six-month follow-up period. Spontaneous esophageal perforation secondary to EoE is a rare but potentially life-threatening complication. This case highlights that conservative management may be a viable alternative to surgical or endoscopic intervention not only in early-detected cases but also in carefully selected delayed presentations managed in a multidisciplinary setting. Long-term follow-up remains essential for the early detection and treatment of late complications, such as stricture formation.

We present the case of a 35-year-old male with no known comorbidities who presented with chronic gastrointestinal (GI) and constitutional symptoms and was empirically treated with several antibiotics during multiple clinic visits at different health facilities. The laboratory test sent included a stool GeneXpert, which was positive for Mycobacterium tuberculosis (MTB). CT imaging revealed multiple necrotic abdominal and retroperitoneal lymph nodes, hypoenhancing splenic lesions, a nodo-colonic fistula between the necrotic retroperitoneal lymph nodes and the adjacent colon, and a mild left-sided pleural effusion. Colonoscopy demonstrated caseating discharge from the fistulous tract 40 cm from the anal verge, and histology showed abundant neutrophils and histiocytes with areas of caseous-like necrosis. The patient was diagnosed with disseminated tuberculosis (TB) with newly diagnosed HIV stage 4. Antituberculous therapy was initiated, followed by antiretroviral therapy (ART) two weeks later in accordance with World Health Organization and national treatment guidelines. This case highlights the need for a thorough evaluation of a patient with a history of chronic GI symptoms and the importance of maintaining a high index of suspicion when diagnosing disseminated TB. In TB-endemic regions, a differential diagnosis of TB should be sought in patients presenting with GI and constitutional symptoms, and such symptoms should prompt an HIV test. Imaging plays a pivotal role in identifying key features such as lymphadenopathy and fistulous tracts, and colonoscopy can show a caseating discharge, which should raise suspicion for chronic infectious or granulomatous diseases, including TB. Although rare, nodo-colonic fistula formation can occur as a complication of abdominal TB. Conservative management can be effective in stable patients, potentially avoiding the morbidity of surgical intervention, as demonstrated in this case. Comprehensive management, including prompt initiation of anti-TB therapy, timely ART, prophylaxis for opportunistic infections, and nutritional support, is crucial to optimize outcomes in such complex presentations.

Chronic diarrhea is a digestive disorder with a global prevalence ranging from 3% to 20%. The etiology of chronic diarrhea is complex and can be life-threatening in severe clinical cases. Zinc serves as a vital trace element that plays a pivotal role in stabilizing the intestinal barrier and regulating gut flora. However, previous evidence on the association between dietary zinc intake and chronic diarrhea remains limited. We extracted and analyzed questionnaire, laboratory, and dietary data from the National Health and Nutrition Examination Survey database (2005-2010). Dietary zinc intake was categorized into quartiles to explore its potential association with chronic diarrhea. The correlation between zinc intake and the risk of chronic diarrhea was analyzed using complex sample-weighted statistical methods, including weighted t tests, weighted chi-square tests, one-way regression analysis, and multivariate logistic regression analysis. The findings indicated a significant positive correlation between zinc intake and risk of chronic diarrhea across all 3 adjusted continuous variable models. For categorical variables, the highest zinc intake group (Q4) exhibited an elevated risk of chronic diarrhea compared with the lowest intake group (Q1). A 2-piecewise linear model identified an inflection point of 22.647 mg in the relationship between zinc intake and chronic diarrhea, with a positive correlation observed below this threshold and a negative correlation detected above this cutoff. Our study provides novel insights into the association between dietary zinc intake and risk of chronic diarrhea. A 2-piecewise linear model revealed a complex correlation between the 2, under the influence of the threshold effect.

Acute gastroenteritis, characterized by vomiting and/or diarrhea, places a significant burden on healthcare systems and the economy. Although tobacco is recognized as a risk factor for chronic gastrointestinal (GI) diseases, its role in acute GI morbidity has not been widely investigated in population-based studies. To quantify the independent association between smoking status and 30-day prevalence of acute GI illness involving vomiting and/or diarrhea, adjusting for key confounders. We used nationally representative data from the 2005 to 2010 National Health and Nutrition Examination Survey (n = 12,358 adults aged ≥20 years) to classify smoking status as never, former, or current. The outcome was self-reported GI illness involving vomiting and/or diarrhea in the past 30 days. We employed staged multivariable logistic regression, sequentially adjusting for the following factors: demographics, comorbidities and body mass index, diet, and inflammatory and nutritional biomarkers. Current smokers had a significantly higher prevalence of GI illness (11.3%) than never smokers (7.5%) and former smokers (8.2%) (P < .001). In the fully adjusted models, current smoking was associated with a 52% increase in the odds of GI illness (odds ratio: 1.52; 95% confidence interval: 1.29-1.79; P < .001), whereas former smokers had odds that were 19% higher (odds ratio: 1.19; 95% confidence interval: 1.01-1.41; P = .037). Stratified analyses confirmed consistency across demographic and clinical subgroups (all P-interactions > .05). Active cigarette smoking is an independent risk factor for acute GI morbidity. The reduced risk among former smokers suggests that the harm caused by tobacco can be reversed, thus supporting smoking cessation as a preventive strategy. This study broadens our understanding of smoking-related diseases and provides insights into integrated tobacco control interventions.

In patients presenting with intestinal symptoms who undergo colonoscopy with mucosal sampling, the pathologist plays a central role in identifying the underlying etiology in order to guide appropriate clinical management. However, common intestinal symptoms such as diarrhea are shared by a broad spectrum of conditions, including infectious diseases, functional disorders (e.g., irritable bowel syndrome), inflammatory bowel disease (IBD), drug-induced injury, and metabolic disorders (e.g., diabetes mellitus). Although serological biomarkers may support the diagnostic workup, they are frequently insufficient to establish a definitive diagnosis. Moreover, endoscopic examination may fail to detect significant mucosal abnormalities even when histology reveals disease-specific patterns, as occurs in lymphocytic and collagenous colitis (i.e., microscopic colitis). In this complex diagnostic landscape, histomorphological evaluation represents a crucial element, allowing integration of microscopic findings with clinical and endoscopic data to reach an accurate interpretation. In recent years, accumulating evidence has demonstrated that similar histological patterns of intestinal injury-such as IBD-like architectural and inflammatory changes or eosinophil-rich infiltrates-may be associated with different underlying etiologies. This overlap is particularly relevant in patients treated with novel oncologic therapies, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and emerging treatments such as chimeric antigen receptor T-cell (CAR-T) therapy. In addition, in daily practice, pathology request forms often lack essential clinical, endoscopic, and laboratory information, further increasing the risk of diagnostic misinterpretation and inappropriate disease attribution. To address these challenges, the Italian Group of Digestive Disease Pathology (GIPAD) proposes a pattern-based histological approach for reporting mucosal damage in patients with colitis. In this first paper, we focus on non-chronic patterns of mucosal injury and discuss their principal differential diagnoses, with the aim of supporting standardized reporting and improving clinicopathological correlation.

Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut-brain interaction characterized by chronic abdominal pain associated with altered bowel habits, including constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), mixed (IBS-M), and unsubtyped forms. The pathophysiology of IBS is believed to be multifactorial as it involves dysregulation of the gut-brain axis, visceral hypersensitivity, serotonergic imbalance, epithelial barrier dysfunction, immune activation, dysbiosis, bile acid alterations, in addition to psychosocial stressors. These interacting mechanisms are known to be involved in the generation of persistent symptoms as well as the widely reported clinical heterogeneity of the disease. Current management strategies include dietary modification, psychological therapies, microbiota-targeted approaches, and pharmacological agents targeting the prevalent symptom subtype. However, treatment responses remain variable, and many patients seek complementary and natural interventions to alleviate their symptoms. Emerging evidence suggests that natural products may exert therapeutic benefits through anti-inflammatory actions, modulation of serotonergic signaling, improvement of intestinal barrier integrity, microbiota regulation, and neuromodulatory effects. Clinical studies demonstrate that certain natural interventions, particularly peppermint oil, STW 5 (Iberogast), psyllium, and several selected probiotics, can provide modest but clinically meaningful symptom improvement, especially for abdominal pain. Nonetheless, heterogeneity in trial design, short durations, small sample sizes, and limited subtype stratification restrict the strength of the resulting recommendations. This review provides a comprehensive overview of IBS pathophysiology, current treatment strategies, and mechanistic and clinical evidence supporting natural products in IBS management, while highlighting critical gaps and future research priorities.

Very early-onset inflammatory bowel disease (VEO-IBD) is frequently triggered by monogenic defects in the pathways responsible for immune system regulation, including mutations in the interleukin-10 receptor alpha (IL-10RA) gene. Patients often show severe and refractory clinical manifestations. Thalidomide has shown immunomodulatory effects in pediatric IBD; however, its immunological effects in IL-10RA-associated VEO-IBD remain poorly defined.

Environmental antibiotic pollution is an underexplored contributor to gut aging and chronic intestinal diseases. We provide evidence that chronic exposure to enrofloxacin (ENR), a commonly detected veterinary antibiotic, accelerates gut aging and disease progression through a mitochondria-centered mechanism. In a population-based cross-sectional analysis, recent antibiotic use was associated with increased biological age and a higher risk of diarrhea in middle-aged and older adults, supporting a link between antibiotic exposure and impaired gut health and aging processes. Using zebrafish and intestinal epithelial cell models, we demonstrate that low-dose ENR exposure impairs intestinal function, characterized by increased permeability, reduced mucus secretion, tight junction disruption, and chronic inflammation. Multi-omics profiling revealed that ENR induced gut microbial dysbiosis, reduced metabolic diversity, and intestinal hypoxia. Mitochondrial dysfunction, particularly impaired oxidative phosphorylation, was identified as the key driver of epithelial damage. Remarkably, treatment with pyrroloquinoline quinone, a mitochondrial-targeted antioxidant, reversed ENR-induced mitochondrial injury, restored intestinal integrity, reduced inflammation, and partially normalized the microbiome. Stratified analyses in the human cohort showed that higher gut microbiota-related diet quality and antioxidant capacity mitigated antibiotic-associated aging and diarrhea risk. These findings highlight mitochondrial protection and microbiota optimization as promising therapeutic strategies.

Severe combined immunodeficiency (SCID) comprises a group of life-threatening inborn errors of immunity (IEI) characterized by profound T-cell deficiency, frequently accompanied by impaired B cell and natural killer (NK) cell function. X-linked SCID (X-SCID), caused by pathogenic variants in IL2RG, accounts for approximately 30% of all SCID cases.

Pivotal clinical studies of new anti-infective drugs enrol patients with strictly defined clinical syndromes, with clinical and laboratory endpoints used to define treatment success. Assessing bacterial killing in the host by serial quantitation has potential as a more efficient pharmacometric approach to assess antibiotic efficacy. We conducted a systematic review of the use of bacterial quantitation in clinical infection. The main syndromes studied in the 222 included articles were bacteraemia, chronic respiratory disease, diarrhoea, pneumonia and sexually transmitted infections. Most reports (135 articles, 61%) quantified bacterial load in different specimen types using quantitative polymerase chain reaction (qPCR). For bacteraemias, bacterial DNA load measured in whole blood by qPCR at clinical presentation was typically 2-3 log10 copies ml-1, usually substantially higher than the estimates from quantitative culture. Higher bacterial loads were associated with increased mortality in 28 of 35 studies. Faster bacterial clearance was correlated with appropriate antibiotic therapy and improved outcome in the majority of studies. Most studies sampled too infrequently for accurate characterization of bacterial clearance rates. The rate of bacterial clearance from blood or other compartments is an informative pharmacodynamic endpoint in the assessment of antibacterial therapeutic effects, but standardized approaches to assessment are needed based on optimal study design. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.