A 63-year-old male with a history of untreated HIV presented to the emergency room with acute on chronic watery diarrhea, weight loss, fatigue, fever and chills. His vital signs were within normal limits and his abdomen was soft, nondistended and tender to palpation in 4 quadrants without peritonitis. He did not have leukocytosis on presentation. CD4 count was 310. CT scan showed inflammatory changes in the rectum and sigmoid colon. Comprehensive infectious workup was negative for any pathogens including cytomegalovirus (CMV), cryptosporidium, chlamydia, gonorrhea, C. difficile, cryptococcus, tuberculosis (TB) and herpes simplex virus (HSV). Colonoscopy was performed and showed a continuous area of nonbleeding ulcerated mucosa in the rectum, sigmoid, descending and transverse colon (Fig. 1). Pancolonic biopsies revealed active colitis with focal areas of basal plasmacytosis and crypt branching in left colon, suggestive of acute on chronic colitis and possible ulcerative colitis (UC). Gastroenterology and infectious disease were consulted and patient was started on IV methylprednisolone for presumed UC flare. Over the next few weeks, the patient proceeded to develop melena as well as increased lower abdominal and pelvic pain with intermittent fevers despite IV steroid treatment. The patient was trialed on IV infliximab also without significant improvement. After several weeks of steroid and biologic treatment, he developed increased abdominal pain with tachycardia and hemodynamic instability. His examination was significant for peritonitis with abdominal distension concerning for fulminant colitis. Colorectal surgery was consulted and proceeded to do an emergent total abdominal colectomy and end ileostomy. Intraoperatively he was found to have a small anterior distal rectal perforation. The decision was made to drain this area widely with rectal drain and fecal diversion and start him on IV antibiotic therapy. His final pathology from the index operation showed ulceration and acute colitis. There was no chronic crypt architectural distortion such as crypt dropout, disarray, crypt branching or basal plasmacytosis that are often seen in inflammatory bowel disease (IBD). There was also increased apoptotic bodies and mitoses that were not consistent with IBD. After reviewing the clinical presentation, his disease progression, and final pathology, the treating team diagnosed the patient with HIV-associated colitis.

We previously demonstrated that anemoside B4 (AB4) exerts a beneficial effect in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis (UC). In this study, we further explored the mechanism of AB4 against UC from the perspective of gut microbiota-immune interplay. The gut microbiota was depleted in two DSS-induced colitis models to investigate the modulatory effects of the gut microbiome on immune responses and the activity of AB4. In parallel, adoptive transfer of CD4[Formula: see text]CD62L[Formula: see text] T cells into Rag1-deficient (Rag1-/-) mice was used to elucidate the alterations in the gut microbiota associated with immune-mediated colitis as well as the modulation by AB4. qPCR, ELISA and western blotting were used to determine the inflammatory responses of mice with colitis, while immunohistochemistry and flow cytometry were employed to determine the CD4[Formula: see text] T cell function and the underlying mechanism. Metagenomic sequencing analysis was used to detect changes in the intestinal microbiota. The depletion of the gut microbiota attenuated disease severity and immune responses in mice with DSS-induced acute and chronic colitis. Notably, the inhibitory effects of orally administered AB4 on colitis progression and immune responses were abrogated. In addition, colitis induced by adoptive transfer of CD4[Formula: see text]CD62L[Formula: see text] T cells into Rag1-/- mice was accompanied by CD4[Formula: see text] T cell engraftment and alterations in gut microbiota. Remarkably, all these pathological changes were significantly attenuated by AB4. Crucially, we found that AB4 suppresses the proliferation, migration, and differentiation of CD4[Formula: see text] T cells, which provides a mechanistic basis for its immunosuppressive effects. Collectively, these findings indicate that the gut microbiota and the immune system, particularly CD4[Formula: see text] T cells, interact with each other in the initiation of colitis. We show that, by targeting this gut microbiota-immune interplay, AB4 is a promising therapeutic strategy for UC.

The gut microbiota is increasingly recognized as a key mediator of the anticolitis effects of curcumin (CUR). However, the clinical translation of this promising activity is severely hampered by CUR's low solubility and poor bioavailability. Although nanoencapsulation represents a promising strategy to address these limitations, the preventive effect of nanocurcumin (nano-CUR) against colitis remains largely unexplored. The present study aimed to elucidate the preventive effects of nano-CUR on intestinal barrier function, gut microbiota composition, and metabolic profiles in a murine model of dextran sulfate sodium (DSS)-induced colitis. The results demonstrated that pre-supplementation of nano-CUR significantly ameliorated disease severity, attenuated intestinal barrier disruption, and suppressed colonic inflammation in mice with DSS-induced colitis. Mechanistically, integrated 16S rRNA sequencing and untargeted metabolomics demonstrated that nano-CUR-restored microbial homeostasis and enhanced the production of short-chain fatty acids, linking microbial shifts to anti-inflammatory outcomes. Fecal microbiota transplantation (FMT) further validated the causal role of the nano-CUR-remodeled microbiota in conferring protection. Collectively, these findings decipher the mechanism by which nano-CUR interacts with the gut microbiota, confirming that dietary nano-CUR consumption protects against ulcerative colitis by modulating the gut microbiome and its metabolic output.

Ulcerative colitis (UC) is driven by excessive oxidative stress, persistent inflammation, and gut microbial dysbiosis, but current treatments often yield limited benefits and cause unwanted systemic adverse effects. In this study, carbon dots (NC-CDs) were synthesized from naringenin and citric acid through a simple one-step hydrothermal method. The obtained NC-CDs are uniformly sized at approximately 3 nm with abundant surface oxygen-containing groups, affording good water solubility and robust free radical scavenging activity. In vitro tests confirmed the favorable biocompatibility of NC-CDs, which effectively eliminated intracellular ROS and inhibited the production of pro-inflammatory cytokines. In a DSS-induced colitis mouse model, oral NC-CDs selectively accumulated in inflamed colonic regions, thereby relieving mucosal damage, improving colitis symptoms, and recovering gut microbial balance. In comparison with an uncarbonized naringenin-citric acid precursor mixture, NC-CDs exhibit superior therapeutic efficacy, demonstrating that the unique nanostructure of carbon dots, rather than simple free small-molecule precursors, contributes to the potent anti-colitis performance. This work suggests that carbon dots derived from natural compounds are promising therapeutic agents for UC treatment.

A patient with ulcerative colitis presented with progressive memory impairment and alexia, with brain imaging showing a mass-like lesion mimicking glioma. Histopathology confirmed central nervous system (CNS) vasculitis. The patient's memory and reading ability improved and finally recovered following corticosteroid treatment, with no recurrence during the long-term follow-up. The case report and literature review highlight that clinicians should consider CNS vasculitis in patients with ulcerative colitis and tumor-like brain lesions.

The role of eicosapentaenoic acid (EPA) in improving ulcerative colitis (UC) has been extensively studied. EPA-acylated astaxanthin (EA), a novel fish oil, has unclear effects on UC. This study constructed a DSS-induced chronic-like relapsing colitis model in mice induced by 2% dextran sulfate sodium (DSS) and primarily concentrated on the changes in gut microbiota and intestinal bile acids (BA) to investigate the anti-UC mechanisms of EA. The results indicated that EA effectively upregulated the expressions of tight junction proteins, ZO-1 and Occludin, while restraining the triggering of the NLRP3 inflammasome. Additionally, EA treatment increased the diversity of the gut microbiota and increased the proportion of Firmicutes, Actinobacteria, and Bifidobacterium, while decreasing the proportion of Bacteroidota, Proteobacteria, and Enterobacteriaceae, which are related to BA metabolism. The metabolomic analysis of BA indicated that EA elevated the concentrations of secondary BA, such as LCA, UDCA, and TUDCA, while decreasing primary BA, such as CA, CDCA, and β-MCA, thereby activating the intestinal ASBT/FXR/TGR5 pathway. In conclusion, EA alleviated DSS-induced colitis, and this protective effect was associated with the modulation of gut microbiota and BA metabolism. The present results laid the foundation for EA as a prospective functional component for UC.

Biotherapeutics are required to achieve high remission rates in patients with severe ulcerative colitis (UC); however, adverse effects, complex dosing regimens, administration routes, and low patient compliance limit their widespread clinical use. Given the localized nature of UC, this study aimed to develop localized delivery strategies for infliximab (IFX), an anti-tumor necrosis factor-α (TNF-α) monoclonal antibody recommended for moderately-to-severely active UC. Exploiting the intrinsic biocompatibility, mucoadhesion, and protein-entrapment capacity of lipid mesophases (LMPs), IFX was encapsulated within the gel matrix, providing protection against enzymatic and environmental degradation. IFX-LMPs were designed for targeted delivery to inflamed colonic tissues via rectal or oral administration, with oral dosage forms manufactured either by 3D printing or by encapsulation into enteric capsules. A comprehensive physicochemical characterization was performed to elucidate mesophase self-assembly and its relationship with IFX release profiles in biorelevant fluids. The rectal gel demonstrated strong mucoadhesion, while LMP-loaded enteric capsules enabled effective colon targeting. In a prophylactic treatment setting, LMP-based formulations significantly attenuated disease progression and the development of severe inflammation compared with subcutaneous IFX. Overall, this study establishes a biocompatible delivery platform that enables colon-targeted IFX release, representing a promising therapeutic strategy for UC using biotherapeutics.

Xanthogranulomatous pyelonephritis (XGPN) is a rare, chronic granulomatous inflammation that leads to diffuse destruction of the renal parenchyma. This destructive process may be so profound as to infiltrate surrounding tissues and viscera. Although nephrectomy remains the most common option for managing XGPN in adults, we report a case of XGPN in a horseshoe kidney of a 27-year-old woman on active immunosuppressive therapy for inflammatory bowel disease, namely ulcerative colitis. This case was successfully treated conservatively with antimicrobials, with complete resolution of the renal mass and improvement in the general condition and inflammatory markers.