Juvenile idiopathic arthritis (JIA) is the most common condition of chronic rheumatic disease in children. JIA is an autoimmune or autoinflammatory disease, with unclear mechanism and limited treatment efficacy. Recent studies have found a number of alterations in gut microbiota and its metabolites in children with JIA, which are related to the development and progression of JIA. This review focuses on the influence of the gut microbiota and its metabolites on immune function and the intestinal mucosal barrier and discuss the key role of the gut-joint axis in the pathogenesis of JIA and emerging treatment methods based on gut microbiota and its metabolites. This review could help elucidate the pathogenesis of JIA and identify the potential therapeutic targets for the prevention and treatment of JIA.
Humans ; Arthritis, Juvenile/physiopathology* ; Gastrointestinal Microbiome/physiology* ; Child ; Intestinal Mucosa

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*

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls. METHODS: Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test. RESULTS: Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001). CONCLUSIONS Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
Adenosine Triphosphate ; metabolism ; Adult ; Blotting, Western ; Colon ; metabolism ; pathology ; Diarrhea ; enzymology ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; genetics ; physiology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Irritable Bowel Syndrome ; enzymology ; metabolism ; pathology ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism

OBJECTIVETo study the effect of Bifidobacterium on the expression of β-defensin-2 (BD-2) in intestinal tissue of neonatal rats with necrotizing enterocolitis (NEC).

METHODSA total of 40 rats were randomly divided into four groups: normal control, Bifidobacterium control, NEC model, and Bifidobacterium treatment, with 10 rats in each group. A rat model of NEC was induced by hypoxia, cold stimulation, and artificial feeding. The rats in the Bifidobacterium control and Bifidobacterium treatment groups were given Bifidobacterium via the gastric tube after cold stimulation once a day for three consecutive days. The morphological changes of the terminal ileum were observed under a light microscope and the intestinal injury score was determined. Immunohistochemistry and qRT-PCR were used to measure the protein and mRNA expression of BD-2 in the ileal mucosal tissue.

RESULTSThe NEC model group had a significantly higher intestinal injury score than the normal control, Bifidobacterium control, and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium treatment group had a significantly higher intestinal injury score than the normal control and Bifidobacterium control groups (P<0.05). The mRNA and protein expression of BD-2 in the normal control group was significantly lower than in the Bifidobacterium control, NEC model, and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium control group had significantly higher mRNA and protein expression of BD-2 than the NEC model and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium treatment group had significantly higher mRNA and protein expression of BD-2 than the NEC model group (P<0.05).

CONCLUSIONSBifidobacterium can induce the expression of BD-2 in intestinal tissue of rats and reduce inflammatory response by increasing the expression of BD-2. This provides a protective effect on neonatal rats with NEC.

Animals ; Bifidobacterium ; Disease Models, Animal ; Enterocolitis, Necrotizing ; therapy ; Humans ; Infant, Newborn ; Intestinal Mucosa ; metabolism ; NF-kappa B ; physiology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; physiology ; beta-Defensins ; analysis ; genetics ; physiology

Animals ; Gene Expression Regulation ; physiology ; Gills ; metabolism ; Intestinal Mucosa ; metabolism ; Lancelets ; genetics ; metabolism ; Liver ; metabolism ; MicroRNAs ; biosynthesis ; genetics

To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.
Animals ; Aquaporin 3 ; physiology ; Aquaporins ; Blotting, Western ; Colon ; chemistry ; pathology ; Constipation ; physiopathology ; therapy ; Cyclic AMP ; physiology ; Defecation ; Epithelial Cells ; pathology ; Feces ; chemistry ; Goblet Cells ; pathology ; Intestinal Mucosa ; metabolism ; pathology ; RNA, Messenger ; Rats ; Signal Transduction ; Vasoactive Intestinal Peptide ; administration & dosage ; physiology ; therapeutic use

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.
Animals ; Apoptosis/*physiology ; Claudins/*metabolism ; Colitis/chemically induced/immunology/*physiopathology ; Colon/immunology/physiopathology ; Dextran Sulfate ; Intestinal Mucosa/*physiopathology ; Lactulose/metabolism ; Mannitol/metabolism ; Mannose-Binding Lectin/*immunology ; Permeability ; Rats ; Rats, Sprague-Dawley ; Sucrose/analogs & derivatives/metabolism ; Up-Regulation

No abstract available.
Animals ; Apoptosis/*physiology ; Claudins/*metabolism ; Colitis/*physiopathology ; Intestinal Mucosa/*physiopathology ; Mannose-Binding Lectin/*immunology

OBJECTIVETo observe the effects of astragalus polysaccharide (AP) on the intestinal mucosal morphology, level of secretory IgA (s-IgA) in intestinal mucus, and distribution of T lymphocyte subsets in Peyer's patch in rats with severe scald injury.

METHODSOne hundred and thirty SD rats were divided into sham injury group (SI, sham injured, n = 10), scald group (S, n = 30), low dosage group (LD, n = 30), moderate dosage group (MD, n = 30), and high dosage group (HD, n = 30) according to the random number table. Rats in the latter 4 groups were inflicted with 30% TBSA full-thickness scald on the back. From post injury hour 2, rats in groups LD, MD, and HD were intraperitoneally injected with 0.5 mL AP solution with the dosage of 100, 200, and 300 mg/kg each day respectively, and rats in group S were injected with 0.5 mL normal saline instead. Ten rats from group SI immediately after injury and 10 rats from each of the latter 4 groups on post injury day (PID) 3, 7, 14 were sacrificed, and their intestines were harvested. The morphology of ileal mucosa was examined after HE staining; the level of s-IgA in ileal mucus was determined with double-antibody sandwich ELISA method; the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes in Peyer's patches of intestine were determined with flow cytometer, and the proportion of CD4⁺ to CD8⁺ was calculated. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test.

RESULTS(1) Villi in normal form and intact villus epithelial cells were observed in rats of group SI immediately after injury, while edema of villi and necrosis and desquamation of an enormous amount of villi were observed in groups with scalded rats on PID 3, with significant infiltration of inflammatory cells. On PID 7, no obvious improvement in intestinal mucosal lesion was observed in groups with scalded rats. On PID 14, the pathology in intestinal mucosa of rats remained nearly the same in group S, and it was alleviated obviously in groups LD and MD, and the morphology of intestinal mucosa of rats in group HD was recovered to that of group SI. (2) On PID 3, 7, and 14, the level of s-IgA in intestinal mucus significantly decreased in groups S, LD, MD, and HD [(43 ± 5), (45 ± 5), (46 ± 5) µg/mL; (47 ± 5), (48 ± 5), (49 ± 6) µg/mL; (50 ± 6), (51 ± 5), (52 ± 5) µg/mL; (53 ± 6), (54 ± 5), (55 ± 5) µg/mL] as compared with that of rats in group SI immediately after injury [(69 ± 4) µg/mL, with P values below 0.05]. The level of s-IgA in intestinal mucus of rats in group MD was significantly higher than that in group S at each time point (with P values below 0.05), and that of group HD was significantly higher than that in groups S and LD at each time point (with P values below 0.05). (3) Compared with those of rats in group SI immediately after injury, the proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes significantly decreased in groups with scalded rats at each time point (with P values below 0.05), except for those in group HD on PID 14. The proportion of CD4⁺ T lymphocytes of rats in group LD was significantly higher than that in group S on PID 3 (P < 0.05). The proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes were significantly higher in groups MD and HD than in groups S and LD (except for the proportion of CD4⁺ T lymphocytes in group MD on PID 3 and 14) at each time point (with P values below 0.05). The proportion of CD3⁺ T lymphocytes on PID 7 and 14 and that of CD4⁺ T lymphocytes on PID 3 were significantly higher in group HD than in group MD (with P values below 0.05). Compared with that of rats in group SI immediately after injury, the proportion of CD8⁺ T lymphocytes significantly increased in the other 4 groups at each time point (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group LD on PID 7 and 14 and groups MD and HD at each time point than in group S (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group MD on PID 7 and 14 and group HD at each time point than in group LD (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group HD on PID 7 and 14 than in group MD (with P values below 0.05). On PID 3, 7, and 14, the proportion of CD4⁺ to CD8⁺ was significantly lower in groups S, LD, MD, and HD (0.65 ± 0.11, 0.68 ± 0.13, 0.73 ± 0.22; 0.76 ± 0.15, 0.78 ± 0.14, 0.90 ± 0.10; 0.85 ± 0.21, 0.89 ± 0.18, 1.08 ± 0.19; 0.99 ± 0.20, 1.05 ± 0.21, 1.25 ± 0.23) as compared with that of rats in group SI immediately after injury (1.74 ± 0.20, with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group HD than in group MD on PID 7 (P < 0.05), and the proportion was significantly higher in these two groups than in group S at each time point (with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group MD on PID 14 and group HD at each time point than in group LD (with P values below 0.05). Compared within each group, the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes and the proportion of CD4⁺ to CD8⁺ of rats in groups LD, MD, and HD showed a trend of gradual elevation along with passage of time.

CONCLUSIONSAP can improve the injury to intestinal mucosa and modulate the balance of T lymphocyte subsets in Peyer's patch in a time- and dose-dependent manner, and it can promote s-IgA secretion of intestinal mucosa in a dose-dependent manner.

Animals ; Astragalus Plant ; adverse effects ; Burns ; immunology ; pathology ; physiopathology ; Dose-Response Relationship, Drug ; Immunity, Mucosal ; Immunoglobulin A ; metabolism ; Intestinal Mucosa ; metabolism ; physiology ; Intestine, Small ; metabolism ; Peyer's Patches ; immunology ; physiopathology ; Polysaccharides ; Rats ; Rats, Sprague-Dawley ; Soft Tissue Injuries ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo study the effect of hypoxia on cofilin activation in intestinal epithelial cells and its relation with distribution of tight junction protein zonula occludens 1 (ZO-1).

METHODSThe human intestinal epithelial cell line Caco-2 was used to reproduce monolayer cells. The monolayer-cell specimens were divided into control group (no treatment), hypoxic group ( exposed to hypoxia), and normoxic group (exposed to normoxia) according to the random number table. Western blotting was used to detect the protein expressions of cofilin and phosphorylatedl cofilin (p-cofilin) of cells in normoxic group and hypoxic group exposed to normoxia or hypoxia for 1, 2, 6, 12, and 24 h and control group, with 9 samples in control group and 9 samples at each time point in the other two groups. The other monolayer-cell specimens were divided into hypoxic group (exposed to hypoxia) and control group (no treatment) according to the random number table. Cells in hypoxic group exposed to hypoxia for 1, 2, 6, 12, and 24 h and control group were obtained. Morphology and distribution of F-actin was observd with laser scanning confocal microscopy, the ratio of F-actin to G-actin was determined by fluorescence method, and distribution of ZO-l and cellular morphology were observed with laser scanning confocal microscopy. The sample number of last 3 experiments was respectively 3, 6, and 3 in both hypoxic group (at each time point) and control group. Data were processed with paired ttest, analysis of variance of repeated measurement, and LSD-t test.

RESULTSThe protein expressions of cofilin and p-cofilin of cells between normoxic group exposed to normoxia for 1 to 24 h and control group showed no significant changes (with values from -0.385 to 1.701, t(p-cofilin)values from 0. 040 to 1.538, P values above 0.05). There were no obvious differences in protein expressions of en filmn of cells between hypoxic group exposed to hypoxia for 1 to 24 h and control group ( with values from 1.032 to 2.390, P values above 0.05). Compared with that in control group, the protein expressions of p-cofilin of cells were greatly reduced in hypoxic group exposed to hypoxia for 1 to 24 h (with values from 4.563 to 22.678, P values below 0.01), especially exposed to hypoxia for 24 h. The protein expressions of cofilin of cells between normoxic group and hypoxic group at each time point were close ( with t values from -0.904 to 1.433, P values above 0.05). In hypoxic group, the protein expressions of p-cofilin of cells exposed to hypoxia for 1, 2, 6, 12, and 24 h were 0.87 +/- 08, 0.780 .05, 0.89 +/- 0.07, 0.68+0. 07, and 0.57 +/- 0.06, respectively, significantly lower than those in normoxic group (0.90 +/- 0.07, 0.97 +/- 0.06, 1.00 +/- 0.06, 1.00 +/- 0.05, and 0.99 +/- 0.05, with t values from 3.193 to 16.434, P values below 0.01). In control group, F-actin in the cytoplasm was abundant, most of it was in bunches. The trend of F-actin was disorderly in hypoxic group from being exposed to hypoxia for 1 h, shortened in length or even dissipated. The ratios of F-actin to G-actin of cells in hypoxic group exposed to hypoxia for 12 and 24 h (0.89 +/- 0.12 and 0.84 +/- 0.19) were obviously decreased as compared with that in control group (1. 00, with t values respectively 3. 622 and 3. 577, P values below 0.01). There were no obvious differences in the ratios of F-actin to G-actin of cells between hypoxic group exposed to hypoxia for 1, 2, and 6 h and control group ( with values from 0.447 to 1.526, P values above 0.05). In control group, cells were compact in arrangement, and ZO-1 was distributed continuously along the cytomnembrane. From being exposed to hypoxia for 2 h, cells became irregular in shape in hypoxic group. ZO-1 was distributed in discontinuous fashion along the cytomembrane with breakage in hypoxic group exposed to hypoxia for 24 h.

CONCLUSIONSHypoxia may cause the disorder of dynamic balance between F-actin and G-actin by inducing cofilin activation, which in turn leads to the changes in distribution of tight junction protein ZO-1 in intestinal epithelial cells.

Actin Depolymerizing Factors ; Actins ; Blotting, Western ; Caco-2 Cells ; drug effects ; physiology ; Epithelial Cells ; cytology ; drug effects ; Humans ; Hypoxia ; metabolism ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; Intestines ; Oxygen ; pharmacology ; Tight Junctions ; drug effects ; metabolism ; Zonula Occludens-1 Protein ; metabolism