The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
Humans ; Intestinal Mucosa/cytology* ; Intestine, Small/cytology* ; Animals ; Inflammatory Bowel Diseases/immunology* ; Celiac Disease/immunology* ; Paneth Cells/immunology*

Inflammatory bowel disease is a chronic, idiopathic, and recurrent gastrointestinal disorder with an unclear etiology and uncertain pathogenesis. Traditional treatment strategies rely on frequent administration of high doses of medication to reduce inflammation, whereas these approaches have limitations and may induce potential complications. Therefore, finding more effective and safe therapeutic drugs and methods is particularly important. Plant-derived exosome-like nanovesicles(PDELNs) are nano-sized vesicles with a lipid bilayer structure that are secreted by plant cells. The bioactive molecules contained within, such as lipids, proteins, and nucleic acids, can serve as information carriers, playing a role in the transmission of information and substances between cells and across species. PDELNs can carry and transfer their own bioactive substances or act as carriers for delivering other active components or drugs. Due to the high biocompatibility, low toxicity, and significant bioactivity, PDELNs have garnered widespread attention. Compared with other exosomes, PDELNs are not destroyed in the gastrointestinal tract when taken orally and can reach the intestines. This unique property makes PDELNs a promising oral nanodrug for treating intestinal diseases, showing great potential in this area. This article reviews recent research literature on PDELNs regarding the physicochemical characteristics, extraction and purification methods, functions, application characteristics and mechanisms in the treatment of intestinal diseases, and use as a carrier for treating intestinal diseases, aiming to provide a reference for the use of PDELNs in the treatment of intestinal diseases.
Humans ; Exosomes/metabolism* ; Animals ; Intestinal Diseases/metabolism* ; Plants/metabolism* ; Drug Carriers/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Drug Delivery Systems ; Nanoparticles/chemistry*

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

The gut microbiota is an indispensable symbiotic entity within the human holobiont, serving as a critical regulator of host lipid metabolism homeostasis. Therefore, it has emerged as a central subject of research in the pathophysiology of metabolic disorders. This microbial consortium orchestrates key aspects of host lipid dynamics-including absorption, metabolism, and storage-through multifaceted mechanisms such as the enzymatic processing of dietary polysaccharides, the facilitation of long-chain fatty acid uptake by intestinal epithelial cells (IECs), and the bidirectional modulation of adipose tissue functionality. Mounting evidence underscores that gut microbiota-derived metabolites not only directly mediate canonical lipid metabolic pathways but also interface with host immune pathways, epigenetic machinery, and circadian regulatory systems, thereby establishing an intricate crosstalk that coordinates systemic metabolic outputs. Perturbations in microbial composition (dysbiosis) drive pathological disruptions to lipid homeostasis, serving as a pathogenic driver for conditions such as obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). This review systematically examines the emerging mechanistic insights into the gut microbiota-mediated regulation of intestinal lipid metabolism, while it elucidates its translational implications for understanding metabolic disease pathogenesis and developing targeted therapies.
Humans ; Gastrointestinal Microbiome/physiology* ; Lipid Metabolism ; Animals ; Intestinal Mucosa/metabolism* ; Homeostasis ; Dysbiosis ; Obesity/metabolism* ; Intestines/microbiology* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Metabolic Diseases/metabolism*

Gallbladder-duodenal fistula,a severe complication of cholecystitis caused by gallstones,is clinically rare.Its clinical presentation lacks specificity,and conventional preoperative imaging often fails to establish a definitive diagnosis.This report describes a case where a gallbladder-duodenal fistula was diagnosed using oral microbubble ultrasound contrast agent for gastric-duodenal contrast-enhanced ultrasound,providing a novel approach for diagnosing this condition.
Humans ; Biliary Fistula/diagnostic imaging* ; Contrast Media ; Duodenal Diseases/diagnostic imaging* ; Gallbladder Diseases/diagnostic imaging* ; Intestinal Fistula/diagnostic imaging* ; Ultrasonography

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

Humans ; Tertiary Care Centers ; Singapore ; Endoscopy, Gastrointestinal ; Intestinal Diseases/diagnostic imaging*

The pathogenesis of inflammatory bowel disease (IBD) is not fully elucidated. However, it has been considered that inflammatory macrophages may be involved in the imbalance of the intestinal mucosal immunity to regulate several signaling pathways, leading to IBD progression. The ratio of M1 to M2 subtypes of activated macrophages tends to increase in the inflamed intestinal section. There are challenges in the diagnosis and treatment of IBD, such as unsatisfactory specificity of imaging findings, low drug accumulation in the intestinal lesions, unstable therapeutic efficacy, and drug-related systemic toxicity. Recently developed nanoparticles may provide a new approach for the diagnosis and treatment of IBD. Nanoparticles targeted to macrophages can be used as contrast agents to improve the imaging quality or used as a drug delivery vector to increase the therapeutic efficiency of IBD. This article reviews the research progress on macrophage-targeting nanoparticles for the diagnosis and treatment of IBD to provide a reference for further research and clinical application.
Humans ; Inflammatory Bowel Diseases/therapy* ; Intestines ; Macrophages/metabolism* ; Intestinal Mucosa/pathology* ; Nanoparticles

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal