Immune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of various malignancies, and ICI-associated colitis is one of the most common side effects. Here we report a 55-year-old man with metastatic melanoma who was initially treated with nivolumab-relatlimab. Due to side effects, therapy was transitioned to ipilimumab, followed by combination ipilimumab and nivolumab. Ten days after the third dose of ipilimumab and nivolumab, he presented to the emergency department with nausea, vomiting, bloody diarrhea, and fever. Stool pathogen panel and Clostridioides difficile polymerase chain reaction (PCR) were negative. ICI-associated colitis was suspected clinically, and he was treated with steroids and then one dose of infliximab. However, his condition did not improve, and a colonoscopy was performed, which showed diffuse severe inflammation characterized by adherent blood, altered vascularity, erythema, friability, and granularity in the entire colon. Biopsy showed colonic mucosa with ulceration, cryptitis, crypt abscesses, dilated crypts with flattened epithelium, and focal crypt dropout. The histologic changes were compatible with ICI-associated colitis. Interestingly, cytomegalovirus (CMV) immunostaining showed scattered positive cells. Subsequent plasma CMV PCR was positive. The patient was treated with ganciclovir. The CMV viral load decreased after treatment, and his diarrhea improved. CMV co-infection in patients with treatment-refractory ICI-associated colitis is rare, and our case highlights the importance of clinicopathologic correlation in reaching the diagnosis.

Gemcitabine-induced pseudocellulitis is a noninfectious inflammatory reaction that closely mimics bacterial cellulitis and can result in substantial diagnostic uncertainty and interruptions in cancer care. We report the case of a woman in her mid-seventies with metastatic pancreatic adenocarcinoma who developed recurrent bilateral lower extremity erythema and edema following gemcitabine therapy. The condition resulted in three unplanned hospitalizations, multiple chemotherapy delays, and five courses of broad-spectrum antibiotics, ultimately leading to antibiotic-associated Clostridioides difficile colitis. The diagnosis of gemcitabine-induced pseudocellulitis was established only during the third hospitalization after recognition of the bilateral symmetric distribution, normal inflammatory markers, negative microbiologic cultures, and a reproducible temporal relationship with gemcitabine administration. Gemcitabine was discontinued, supportive measures were initiated, and the patient's symptoms resolved completely. This case highlights the considerable oncologic and healthcare burden associated with delayed recognition of gemcitabine-induced pseudocellulitis and underscores the importance of early diagnosis by the hematology-oncology team to avoid unnecessary hospitalizations, inappropriate antibiotic exposure, and interruptions in cancer-directed therapy.

Boerhaave syndrome (spontaneous esophageal rupture) remains a surgical emergency with high mortality, particularly when complicated by mediastinitis, pleural empyema, and septic shock. Concomitant intra-abdominal perforation significantly increases morbidity. We report a case of a 61-year-old male patient presenting with hemodynamic instability due to distal esophageal rupture and duodenal perforation. Imaging revealed bilateral pneumothorax, pneumomediastinum, pneumoperitoneum, and extensive pleural effusions. The patient underwent emergent exploratory laparotomy with esophageal repair over T-tube placement, mediastinal lavage, primary duodenal repair, bilateral chest tube placement, decompressive gastrostomy, and feeding jejunostomy. The postoperative course was complicated by septic shock, bilateral pleural empyema requiring re-interventions including thoracotomy and pleurodesis, multidrug-resistant pulmonary infections, axillary vein thrombosis, Clostridioides difficile colitis, and prolonged mechanical ventilation. After comprehensive multidisciplinary management in the ICU, gradual respiratory and hemodynamic stabilization was achieved.

Clostridioides difficile (C. difficile) is a leading cause of antibiotic-associated diarrhea and colitis, with hypervirulent or resistant strains and high recurrence, limiting current therapies. Antivirulence therapy presents a promising alternative by neutralizing toxins without damaging the gut microbiota or promoting resistance. Here, we identified myricetin (MYR) and its derivatives, dihydromyricetin, and myricitrin (MYT), which effectively suppressed TcdB-mediated cell rounding. Mechanistically, MYR inhibits TcdB internalization, self-cleavage, and Rac1 glycosylation, thereby reducing the cytotoxicity. Microbiomics demonstrated that MYR promoted the expansion of beneficial bacteria such as Muribaculaceae and Lactobacillaceae while reducing the abundance of harmful bacteria, including Enterococcaceae and Enterobacteriaceae. Metabolomics further revealed that MYR elevated the levels of indole and its derivatives, including castanospermine. Castanospermine supplementation decreased the fecal bacterial load and ameliorated histopathological damage in infected mice. Collectively, MYR exerts dual functions by antagonizing virulence and sustaining microbiota homeostasis, thereby improving outcomes in C. difficile infections.

Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance-particularly during early life-restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications-including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders-remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit.

The gut microbiome, often termed the human "second genome", profoundly influences host physiology through metabolic interactions, immune modulation, and gut-brain axis signaling. Dysbiosis is implicated in the pathogenesis of obesity, inflammatory bowel disease (IBD), malignancies, and neuropsychiatric disorders. However, traditional gut microbiota interventions, such as probiotic supplementation and fecal microbiota transplantation (FMT), still exhibit significant limitations in precision therapeutics. Probiotic intervention fails to achieve precise regulation at the strain or genetic level, and although FMT demonstrates definitive efficacy against recurrent Clostridioides difficile infection (rCDI), its therapeutic outcomes and safety profiles show marked interindividual variability in ulcerative colitis (UC), metabolic syndrome, and other diseases, with insufficient treatment specificity to meet the practical demands of clinical precision intervention. Recent advancements in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) proteins systems and base editors, have enabled targeted functional manipulation of specific gut commensals and optimization of community architectures. These engineered strategies, combined with sophisticated delivery systems, demonstrate substantial potential in disease treatment, diagnostic monitoring, and immune modulation. This review systematically examines core editing methodologies, innovative delivery platforms, and targeted design strategies, elucidating their applications in metabolic disorders, IBD, cancer immunotherapy, and neuropsychiatric conditions. We critically analyze current technical bottlenecks and biosafety concerns while prospecting future directions, including in situ editing, artificial intelligence (AI)-driven design, and personalized engineering. Collectively, these insights aim to facilitate the clinical translation of gut microbiome engineering from bench to bedside.

Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings suggestive of systemic dissemination and public health implications. This study aimed to investigate a fatal case of C. difficile infection in a farmed rabbit and to characterize the pathogen's microbiological, toxigenic, and antimicrobial profile. Methods: An 11-month-old male German Giant Spotted rabbit presenting acute diarrhea, anorexia, and rapid deterioration after unsupervised administration of enrofloxacin and sulfaquinoxaline was submitted postmortem. Necropsy was performed, and samples from cecum, colon, liver, spleen, mesenteric lymph nodes, lungs, and femoral bone marrow were collected. Microbiological analysis included selective culture on CCFA medium, ELISA for toxin A and B detection, MALDI-TOF MS identification, PCR confirmation, and antimicrobial susceptibility testing with the VITEK 2 system. Histopathological examination was conducted on intestinal and parenchymal tissues. Results: Necropsy revealed severe congestion and necrosis of the cecal and colonic mucosa, hepatomegaly, splenic congestion, and petechial hemorrhages. C. difficile was isolated from intestinal sites, confirmed as toxigenic by ELISA and PCR. Histopathology showed necrotizing colitis with epithelial desquamation, fibrin deposition, and heterophilic infiltration. The strain exhibited resistance to clindamycin, ampicillin, and tetracycline, with susceptibility to vancomycin, linezolid, and tigecycline. Conclusions: This case demonstrates that C. difficile can cause severe disease in rabbits, particularly following antimicrobial-induced dysbiosis. The findings underscore the importance of prudent antibiotic use, monitoring of toxigenic strains in rabbit populations, and implementation of preventive strategies to mitigate health risks in both animals and potentially humans.

[This corrects the article DOI: 10.3389/fped.2026.1808589.].

Pseudomembranous colitis due to Clostridioides difficile infection (CDI) is a serious complication of antibiotic therapy and hospitalization that can progress to toxic megacolon, necessitating emergency colectomy. Patients undergoing pancreaticoduodenectomy (PD) are particularly at high risk due to biliary obstruction, recurrent cholangitis, broad-spectrum antibiotic exposure, and prolonged postoperative stays. We report the case of an elderly woman with multiple cardiovascular comorbidities and recent CDI who underwent PD for pancreatic ductal adenocarcinoma (PDAC). Prior to surgery, she had an endoscopic retrograde cholangiopancreatography (ERCP) with duodenobiliary (DB) stent placement due to obstructive jaundice, and biopsies confirmed PDAC. Intravenous cefotaxime was initiated because of signs of acute cholangitis. She subsequently developed CDI and completed treatment with oral vancomycin, which was discontinued only 11 days before the PD. Standard prophylaxis with cefazolin was administered prior to surgery. On postoperative day (POD) 1, empirical antibiotic therapy with cefotaxime was initiated. By POD 3, she developed profuse watery diarrhea, fever, and leukocytosis, with confirmed recurrent CDI. Despite prompt fidaxomicin therapy and intensive care, she rapidly deteriorated. Computed tomography (CT) revealed severe pancolitis and toxic megacolon. Emergency subtotal colectomy with end ileostomy was performed, and histopathological examination confirmed the diagnosis. She eventually stabilized but remained frail, and the tumor board recommended best supportive care instead of adjuvant chemotherapy due to the disease stage and the severe course of CDI. This case underscores the need for early CDI testing in postoperative diarrhea following PD and for cautious perioperative antibiotic strategies in patients with recent CDI, as broad-spectrum antibiotics may precipitate fulminant recurrence.

Clostridioides difficile is a toxin-producing pathogen that opportunistically infects those with a depleted gut microbiome, often triggered by antibiotic use. C. difficile preferentially utilizes Stickland amino acids, including proline, to promote energy generation and growth for colonization. We evaluated host outcomes from infection with wild-type and ΔprdB mouse-infective C. difficile ATCC 43255 strains to investigate how proline metabolism modulates C. difficile's pathogenesis and interactions with commensals in an enriched gut nutrient environment. While gnotobiotic mice infected with the ΔprdB mutant succumbed to infection, they showed delayed colonization and toxin production, thereby extending their survival. In vivo C. difficile transcriptomic analyses demonstrated a shift from Stickland fermentation to carbohydrate metabolism in the ΔprdB mutant. To investigate functions of C. difficile's proline reductase in interactions with the commensal microbiota, we evaluated infection outcomes in mice co-colonized with the disease-promoting commensal Clostridium sardiniense (CSAR). One-third of CSAR and ΔprdB-infected mice survived, while co-colonized mice with the wild-type strain rapidly succumbed within 48 h. In vivo transcriptomic analyses from co-colonized mice identified additional metabolic defects in the ΔprdB mutant, including failure to express oxidative Stickland pathways and ornithine fermentations to harness CSAR-produced ornithine, suggesting conversion of the mutant into a glycolytic strain that was now in direct competition with CSAR for carbohydrate substrates. CSAR remained metabolically active during the ΔprdB infection through its mucin degradation and polysaccharide and disaccharide metabolism. Our findings illustrate critical functions of C. difficile's proline reductase in coordinating early metabolism to facilitate gut colonization, including interactions with a cross-feeding commensal species.

Lupus enteritis is a recognized but uncommon and potentially life-threatening gastrointestinal manifestation of systemic lupus erythematosus. Its symptoms are often nonspecific and may mimic infectious enteritis, pseudomembranous colitis, intestinal obstruction, or a surgical acute abdomen. We report a 19-year-old woman with a prior diagnosis of SLE and irregular use of maintenance therapy who developed abdominal pain, watery diarrhea, nausea, vomiting, and progressive abdominal distension after ingestion of suspected contaminated food. During hospitalization, she passed large amounts of clear, gelatinous, pseudomembrane-like stool material. Laboratory evaluation showed anemia, thrombocytopenia, hypocomplementemia, positive antinuclear antibodies, positive anti-Ro52 antibodies, and negative microbiological studies, including stool culture and Clostridioides difficile toxin assays. Contrast-enhanced abdominal computed tomography demonstrated segmental small-bowel wall thickening with the target sign, mesenteric vascular engorgement with the comb sign, and ascites, supporting the diagnosis of lupus enteritis. After infection was considered unlikely, empirical antibiotics were discontinued. High-dose intravenous methylprednisolone, adjunctive intravenous immunoglobulin, and cyclophosphamide led to rapid clinical improvement within 48-72 hours, with subsequent radiological resolution. The novelty of this case lies not in lupus enteritis itself, but in its presentation with substantial clear gelatinous pseudomembrane-like stool material, a rarely emphasized manifestation that may mislead clinicians toward infectious or pseudomembranous colitis. Early recognition based on SLE activity, characteristic CT findings, exclusion of infection, and multidisciplinary assessment is essential to avoid diagnostic delay and prevent severe complications.

This review combines historical reports and surveillance data to contextualize Clostridioides difficile infection (CDI) in the U.S. as a phased epidemic, currently in the deceleration phase. C. difficile was first isolated in 1935. During a prolonged emergence phase, the organism attracted limited clinical attention. In 1978, C. difficile was established as the cause of antibiotic-associated pseudomembranous colitis and from 1978 to a peak in 2010, CDI was in an acceleration phase characterized by fluoroquinolone-resistant, toxin-overproducing strains, large hospital outbreaks, and incidence rates over 150 per 100,000 population. Beginning around 2010, CDI incidence decreased, with a shift from healthcare-associated to community-acquired CDI. Changes in diagnostics complicate incidence comparison between phases; only recently is it apparent that CDI has entered a deceleration phase characterized by infectious reservoirs and possible increases in immunity. It may behoove us to prepare for a different kind of CDI: community-based and insidious rather than hospital-predominant and explosive.