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1.
Ann Clin Lab Sci ; 52(2): 301-313, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35414509

RESUMO

OBJECTIVE: Genkwanin is a biologically active O-methylated flavone extracted from Daphne genkwa. An increasing number of studies have described the modulatory effects of genkwanin on human diseases, including antitumor, anti-inflammatory, and antioxidant activities. However, little is known about whether genkwanin might be a therapeutic agent for inflammatory bowel disease or its possible underlying mechanisms. MATERIALS AND METHODS: Forty C57BL/6 male mice were orally administered dextran sulfate sodium (DSS) to generate the colitis model, and genkwanin was orally administered at the indicated concentrations. Body weight, disease activity index, colon length, and H&E staining were used to evaluate colitis. Oxidative stress and antioxidant levels were measured by detecting ROS generation and malondialdehyde, superoxide dismutase and glutathione levels. The levels of proinflammatory cytokines (TNF-α, IL-1ß, IFNγ and IL-6) were measured using ELISAs. Cell viability was determined using the CCK-8 assay. Mitochondrial function was evaluated by measuring the oxygen consumption rate, mtDNA content, and activities of electron transfer chain (ETC) complexes I, II, and IV. The expression of SIRT1, Nrf2 and its target genes was determined using qRT-PCR and western blotting. SIRT1 was depleted by lentivirus-mediated knockdown. RESULTS: In this study, oral administration of genkwanin alleviated colitis induced by oral administration of DSS in mice, as evidenced by reduced weight loss, colon length shortening and histopathology scores. Furthermore, genkwanin relieved oxidative stress and reduced the production of proinflammatory cytokines. In vitro assays revealed that genkwanin administration inhibited reactive oxygen species (ROS) production and improved mitochondrial function in human intestinal epithelial cells. Genkwanin also upregulated the expression of SIRT1, and lentivirus-mediated SIRT1 knockdown partially abrogated the protective effect of genkwanin on oxidative stress and mitochondrial dysfunction. CONCLUSIONS: Findings from our murine model and cell culture experiments provide a promising basis for genkwanin to be studied as a treatment for IBD in clinical trials.


Assuntos
Colite , Sirtuína 1 , Animais , Antioxidantes/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Flavonas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo
2.
Food Chem ; 387: 132807, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35397273

RESUMO

A water-soluble dietary fiber named BSDF-1 (polysaccharide) was isolated from the bamboo (Phyllostachys edulis) shoot. BSDF-1was characterized as a backbone consisting predominately of 1,4-linked Glcp, and the protective effects and mechanisms of the anti-inflammatory activity were investigated using a dextran sulfate sodium (DSS)-induced colitis mouse model. BSDF-1 administration significantly reduced colonic pathological damage, inhibited the activation of inflammatory signaling pathways, including nuclear factor-kappa B and NLR family pyrin domain containing 3 inflammasomes pathways. It restored the mRNA expression of tight junction proteins, including zonula occludens-1, claudin-1, and occludin. Furthermore, BSDF-1 treatment reduced Parabacteroides, Mucispirillum, Helicobacter, Bacteroides, and Streptococcus levels, whereas high-dose BSDF-1 treatment increased Prevotella, Alitipes, Anaerostipes, Odoribacter, Bifidobacterium, Butyricimonas, and Lactobacillus levels. In conclusion, BSDF-1 can inhibit the activation of inflammatory signaling pathways and restore the intestinal barrier function. Thus, BSDF-1 may be a valuable food supplement or nutraceutical to manage and prevent ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colite Ulcerativa/tratamento farmacológico , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/metabolismo
3.
Nutrients ; 14(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458125

RESUMO

Vitamin A (VA) deficiency and diarrheal diseases are both serious public health issues worldwide. VA deficiency is associated with impaired intestinal barrier function and increased risk of mucosal infection-related mortality. The bioactive form of VA, retinoic acid, is a well-known regulator of mucosal integrity. Using Citrobacter rodentium-infected mice as a model for diarrheal diseases in humans, previous studies showed that VA-deficient (VAD) mice failed to clear C. rodentium as compared to their VA-sufficient (VAS) counterparts. However, the distinct intestinal gene responses that are dependent on the host's VA status still need to be discovered. The mRNAs extracted from the small intestine (SI) and the colon were sequenced and analyzed on three levels: differential gene expression, enrichment, and co-expression. C. rodentium infection interacted differentially with VA status to alter colon gene expression. Novel functional categories downregulated by this pathogen were identified, highlighted by genes related to the metabolism of VA, vitamin D, and ion transport, including improper upregulation of Cl- secretion and disrupted HCO3- metabolism. Our results suggest that derangement of micronutrient metabolism and ion transport, together with the compromised immune responses in VAD hosts, may be responsible for the higher mortality to C. rodentium under conditions of inadequate VA.


Assuntos
Infecções por Enterobacteriaceae , Deficiência de Vitamina A , Animais , Citrobacter rodentium , Colo/metabolismo , Diarreia/complicações , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Vitamina A/metabolismo , Deficiência de Vitamina A/complicações
4.
Food Funct ; 13(9): 5115-5123, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35416187

RESUMO

Inflammatory bowel disease (IBD) characterized by relapsed intestinal inflammation and barrier function disruption is still a great therapeutic challenge. This study aimed to screen probiotics that have the potential to help alleviate IBD and further elucidate their mechanism of action. Caco-2 cell differentiated monolayers and RAW264.7 cells stimulated by lipopolysaccharide (LPS) were used for probiotic screening in vitro, and then the efficacies of the obtained six bacterial strains were evaluated in mice with dextran sulfate sodium (DSS)-induced colitis. The results showed that all of the strains at varying degrees could increase the transepithelial electrical resistance (TEER) value, decrease the influx of FITC-dextran in Caco-2 cell monolayers and attenuate the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated RAW264.7 cells. In vivo experiments indicated that Bifidobacterium bifidum FL-276.1 (FL-276.1) and Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best efficacies to ameliorate body weight loss, colon shortening, and intestinal barrier disruption. Accordingly, in FL-276.1 and FL-228.1 groups, the genes of zonula occludens-1 (ZO-1), claudin-4, occludin and mucin 2 (Muc2) in mouse colonic tissues were significantly upregulated, while TNF-α, IL-1ß and IL-6 were downregulated. Further results showed that strains FL-276.1 and FL-228.1 could activate the aryl hydrocarbon receptor (AhR) in the intestine. Our study showed that the two Bifidobacterium bifidum strains, FL-276.1 and FL-228.1, ameliorated DSS-induced colitis by enhancing the intestinal barrier and anti-inflammation potentially via the AhR pathway.


Assuntos
Bifidobacterium bifidum , Colite , Doenças Inflamatórias Intestinais , Animais , Bifidobacterium bifidum/metabolismo , Células CACO-2 , Colite/induzido quimicamente , Colite/genética , Colite/terapia , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
J Agric Food Chem ; 70(16): 4952-4965, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35412826

RESUMO

Inflammatory bowel disease (IBD) poses a threat to health and compromises the immune system and gut microflora. The present study aimed to explore the effects of rice protein (RP) purified from rice dregs (RD) on acute colitis induced by dextran sulfate sodium (DSS) and the underlying mechanisms. Results showed that RP treatment could alleviate the loss of body weight, colon shortening and injury, and the level of disease activity index, repair colonic function (claudin-1, ZO-1 and occludin), regulate inflammatory factors, and restore oxidative balance (malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capability (T-AOC)) in mice. Also, RP treatment could activate the Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, mediate the expression of downstream antioxidant protease (NQO-1, HO-1, and Gclc), regulate gut microbiota by enhancing the relative abundance of Akkermansia and increasing the value of F/B, and adjust short-chain fatty acid levels to alleviate DSS-induced colitis in mice. Thus, RP may be an effective therapeutic dietary resource for ulcerative colitis.


Assuntos
Colite , Microbioma Gastrointestinal , Oryza , Animais , Antioxidantes/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo/metabolismo , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Oryza/metabolismo , Estresse Oxidativo
6.
Cells ; 11(7)2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35406708

RESUMO

Organoids represent the cellular composition of natural tissue. So called colonoids, organoids derived from colon tissue, are a good model for understanding regeneration. However, next to the cellular composition, the surrounding matrix, the cell-cell interactions, and environmental factors have to be considered. This requires new approaches for the manipulation of a colonoid. Of key interest is the precise application of localized damage and the following cellular reaction. We have established multiphoton imaging in combination with femtosecond laser-based cellular nanosurgery in colonoids to ablate single cells in the colonoids' crypts, the proliferative zones, and the differentiated zones. We observed that half of the colonoids recovered within six hours after manipulation. An invagination of the damaged cell and closing of the structure was observed. In about a third of the cases of targeted crypt damage, it caused a stop in crypt proliferation. In the majority of colonoids ablated in the crypt, the damage led to an increase in Wnt signalling, indicated via a fluorescent lentiviral biosensor. qRT-PCR analysis showed increased expression of various proliferation and Wnt-associated genes in response to damage. Our new model of probing colonoid regeneration paves the way to better understand organoid dynamics on a single cell level.


Assuntos
Colo , Organoides , Comunicação Celular , Diferenciação Celular , Colo/metabolismo , Lasers , Organoides/metabolismo
7.
Commun Biol ; 5(1): 370, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440795

RESUMO

The obesity epidemic continues to worsen worldwide. However, the mechanisms initiating glucose dysregulation in obesity remain poorly understood. We assessed the role that colonic macrophage subpopulations play in glucose homeostasis in mice fed a high-fat diet (HFD). Concurrent with glucose intolerance, pro-inflammatory/monocyte-derived colonic macrophages increased in mice fed a HFD. A link between macrophage numbers and glycemia was established by pharmacological dose-dependent ablation of macrophages. In particular, colon-specific macrophage depletion by intrarectal clodronate liposomes improved glucose tolerance, insulin sensitivity, and insulin secretion capacity. Colonic macrophage activation upon HFD was characterized by an interferon response and a change in mitochondrial metabolism, which converged in mTOR as a common regulator. Colon-specific mTOR inhibition reduced pro-inflammatory macrophages and ameliorated insulin secretion capacity, similar to colon-specific macrophage depletion, but did not affect insulin sensitivity. Thus, pharmacological targeting of colonic macrophages could become a potential therapy in obesity to improve glycemic control.


Assuntos
Dieta Hiperlipídica , Resistência à Insulina , Animais , Glicemia/metabolismo , Colo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Controle Glicêmico , Macrófagos/metabolismo , Camundongos , Obesidade/etiologia , Obesidade/metabolismo , Serina-Treonina Quinases TOR/metabolismo
8.
Comput Math Methods Med ; 2022: 1353724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371288

RESUMO

Objective: This study was to define the protective effect of purified Helvella leucopus polysaccharide (p-HLP) against dextran sulfate sodium- (DSS-) induced colitis. Methods: The novel p-HLP was isolated from Bachu mushroom through hot water extraction, ethanol precipitation, and column chromatography. Then, we evaluated the potential effects of p-HLP on colonic histopathology, inflammation, and microbiota composition in DSS-induced colitis mice. Results: p-HLP was a homopolysaccharide with an average molecular weight of 39.14 × 108 Da. Functionally, p-HLP significantly attenuated DSS-induced body weight loss and colon shortening. The histological score of the colon lesion was significantly decreased upon p-HLP treatment. Also, p-HLP treatment led to decreased expression of proinflammatory cytokines and mediators (IL-6, IL-1ß and TNF-α, and COX-2 and iNOS) and increased expression of anti-inflammatory cytokine (IL-10) in the colon tissues. Illumina MiSeq sequencing revealed that p-HLP modulated the composition of the gut microbiota. Conclusion: p-HLP is a potent regulator that protects the lesions from DSS-induced colitis.


Assuntos
Agaricales , Microbioma Gastrointestinal , Animais , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana/metabolismo , Sulfato de Dextrana/farmacologia , Humanos , Camundongos , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia
9.
Int J Mol Sci ; 23(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408884

RESUMO

GLP1 produced in the upper part of the gut is released after food intake and acts by activating insulin secretion, but the role of GLP1 in the colon, where it is predominantly produced, remains unknown. Here we characterized the apical versus basolateral secretion of GLP1 and PYY and the paracrine mechanisms of action of these enterohormones in the human colon. We stimulated human colon tissue in different ex vivo models with meat peptone and we used immunofluorescence to study the presence of canonical and non-canonical receptors of GLP1. We found that PYY and GLP1 are secreted mainly at the gut lumen in unstimulated and stimulated conditions. We detected DPP4 activity and found that GLP1R and GCGR are widely expressed in the human colon epithelium. Unlike GLP1R, GCGR is not expressed in the lamina propria, but it is located in the crypts of Lieberkühn. We detected GLP1R expression in human colon cell culture models. We show that the apical secretion of PYY and GLP1 occurs in humans, and we provide evidence that GLP1 has a potential direct paracrine function through the expression of its receptors in the colon epithelium, opening new therapeutic perspectives in the use of enterohormones analogues in metabolic pathologies.


Assuntos
Colo , Receptor do Peptídeo Semelhante ao Glucagon 1 , Colo/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Secreção de Insulina , Mucosa Intestinal/metabolismo
10.
Biochem Biophys Res Commun ; 604: 96-103, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35303685

RESUMO

Different regions and states of the human colon are likely to have a distinct influence on immune cell functions. Here we studied the immunometabolic mechanisms for spatial immune specialization and dysregulated immune response during ulcerative colitis at single-cell resolution. We revealed that the macrophages and CD8+ T cells in the lamina propria of the human colon possessed an effector phenotype and were more activated, while their lipid metabolism was suppressed compared with those in the epithelial. Also, IgA+ plasma cells accumulated in lamina propria of the sigmoid colon were identified to be more metabolically activated versus those in the cecum and transverse colon, and the improved metabolic activity was correlated with the expression of CD27. In addition to the immunometabolic reprogramming caused by spatial localization colon, we found dysregulated cellular metabolism was related to the impaired immune functions of macrophages and dendritic cells in patients with ulcerative colitis. The cluster of OSM+ inflammatory monocytes was also identified to play its role in resistance to anti-TNF treatment, and we explored targeted metabolic reactions that could reprogram them to a normal state. Altogether, this study revealed a landscape of metabolic reprogramming of human colonic immune cells in different locations and disease states, and offered new insights into treating ulcerative colitis by immunometabolic modulation.


Assuntos
Colite Ulcerativa , Linfócitos T CD8-Positivos , Colo/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Análise de Célula Única , Inibidores do Fator de Necrose Tumoral
11.
Life Sci ; 298: 120494, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35339510

RESUMO

AIMS: Chronic kidney disease (CKD) produces multiple repercussions in the gastrointestinal tract (GIT), such as alterations in motility, gut microbiota, intestinal permeability, and increased oxidative stress. However, despite enteric glial cells (EGC) having important neural and immune features in GIT physiology, their function in CKD remains unknown. The present study investigates colonic glial markers, inflammation, and antioxidant parameters in a CKD model. MAIN METHODS: A 5/6 nephrectomized rat model was used to induce CKD in rats and Sham-operated animals as a control to suppress. Biochemical measures in plasma and neuromuscular layer such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were carried out. Kidney histopathology was evaluated. Colon morphology analysis and glial fibrillary acid protein (GFAP), connexin-43 (Cx43), nuclear factor-kappa B (NF-κB) p65, and GPx protein expression were performed. KEY FINDINGS: The CKD group exhibited dilated tubules and tubulointerstitial fibrosis in the reminiscent kidney (p = 0.0002). CKD rats showed higher SOD activity (p = 0.004) in plasma, with no differences in neuromuscular layer (p = 0.9833). However, GPx activity was decreased in the CKD group in plasma (p = 0.013) and neuromuscular layer (p = 0.0338). Morphological analysis revealed alterations in colonic morphometry with inflammatory foci in the submucosal layer and neuromuscular layer straightness in CKD rats (p = 0.0291). In addition, GFAP, Cx43, NF-κBp65 protein expression were increased, and GPx decreased in the neuromuscular layer of the CKD group (p < 0.05). SIGNIFICANCE: CKD animals present alterations in colonic cytoarchitecture and decreased layer thickness. Moreover, CKD affects the enteric glial network of the neuromuscular layer, associated with decreased antioxidant activity and inflammation.


Assuntos
Antioxidantes , Insuficiência Renal Crônica , Animais , Antioxidantes/metabolismo , Colo/metabolismo , Conexina 43/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Inflamação/patologia , Masculino , Nefrectomia , Neuroglia/metabolismo , Ratos , Insuficiência Renal Crônica/metabolismo , Superóxido Dismutase/metabolismo
12.
Am J Physiol Gastrointest Liver Physiol ; 322(5): G480-G488, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35258349

RESUMO

Bile acids are amphipathic, detergent molecules. The detergent effects of di-α-hydroxy-bile acids are relevant to several colonic diseases. The aims were to review the concentrations of bile acids reaching the human colon in health and disease, the molecular structure of bile acids that determine detergent functions and the relationship to human diseases (neuroendocrine tumors, microscopic colitis, active celiac disease, and ulcerative colitis, Crohn's disease and ileal resection), the relationship to bacterial uptake into the mucosa, mucin depletion, and epithelial damage, the role of bile acids in mucosal inflammation and microscopic colitis, and the role of sulfation of bile salts in detoxification or prevention of the detergent effects of bile acids. The concentrations of bile acids reaching the human colon range from 2 to 10 mM; di-α-hydroxy bile acids are the only bile acids with detergent effects that include mucin depletion, mucosal damage, bacterial uptake, and microscopic inflammation that may be manifest in diseases associated with no overt inflammation of the mucosa, such as bile acid diarrhea, ileal diseases such as neuroendocrine tumors, ileal resection, and nonalcoholic steatohepatitis. Sulfation inactivates colonic secretion due to primary bile acids, but it may render secondary bile acids proinflammatory in the colon. Other evidence in preclinical models of inflammatory bowel disease (IBD) suggests reduced sulfation causes barrier dysfunction, inflammation, or carcinogenesis. These advances emphasize relevance and opportunities afforded by greater understanding of the chemistry and metabolism of bile acids, which stands to be further enhanced by research into the metabolic interactions of microbiota with bile acids.


Assuntos
Ácidos e Sais Biliares , Mucosa Intestinal , Ácidos e Sais Biliares/metabolismo , Colo/metabolismo , Humanos , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Permeabilidade
13.
Food Funct ; 13(8): 4399-4420, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35297435

RESUMO

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon with a continuously remitting and relapsing course. Its etiology is closely related to abnormal interactions between host and gut microbiota. The mucus barrier lining the gastrointestinal tract is necessary to coordinate host and gut microbiota interaction by nourishing and modulating the microbiota. Differential effects of the anti-inflammatory fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on UC progression in mice were firstly addressed by our previous work; here, the mechanism for their respective effects were further uncovered from host-microbiome crosstalk based on mucus barrier modulation to pave the way for UC therapy. Methods: Assessment of the disease activity index and histopathology score was conducted in mice with dextran sodium sulfate (DSS)-induced colitis pre-treated with different doses of EPA and DHA. Mucin generation, glycosylation and secretion were evaluated by a combination of electron microscopy, specific mucous staining, and qPCR. Western blotting was used to analyze the underlying molecular events. Fecal short chain fatty acids were detected using gas chromatography, and the gut microbial composition was analyzed using 16S rRNA sequencing. Results: Compared with DHA, the more potent inhibitory effect of high dose EPA on DSS-induced colitis was reconfirmed, which was underlain by a reinforced mucus layer as indicated by increased mucin granule release, mucus layer stratification and markedly upregulated expression of the key modulators involved in goblet cell differentiation. In turn a remarkably enhanced mucus barrier in the EPA group functioned to modulate the gut microbiome, as demonstrated by the enriched abundance of the phylum Bacteroidetes and mucin-degrading bacterium Akkermansia muciniphila producing acetic and propionic acids. Conclusions: EPA and DHA differentially coordinate the interaction between the host and the gut microbiota and relieve mucus barrier disruption in DSS-induced colitis. EPA may develop into a promising adjunctive therapy for UC.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Colite Ulcerativa/tratamento farmacológico , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Mucinas/metabolismo , Muco/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Verrucomicrobia
14.
Food Funct ; 13(8): 4384-4398, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35297441

RESUMO

This study investigated the anti-inflammatory effects of cyanidin-3-glucoside (C3G) and blueberry pectin (BP) complexes on mice with dextran sodium sulfate (DSS)-induced colitis before and after high hydrostatic pressure (HHP) treatment. Real-time polymerase chain reaction (RT-PCR), western blotting, and 16S rDNA sequencing were used to study the expression of inflammation-related factors, activation of signal pathway-related proteins, and changes in the intestinal flora in ulcerative colitis (UC) mice. The results showed that HHP-treated C3G-BP complexes significantly relieved diarrhea and blood loss in the stool of UC mice and alleviated colon shortening. The potential mechanism of action involved reduction in intestinal oxidative stress mRNA expression of pro-inflammatory factors, improvement in anti-inflammatory factor levels, inhibition of the NF-κB signaling pathway, increased protein levels of Bcl-2/Bax and caspase-3/cleaved caspase-3 genes, and improved gut microbiota composition. Compared with other experimental groups, the HHP-treated C3G-BP complexes group exhibited the best anti-inflammatory effect on DSS-induced UC mice. The results may provide new ideas for using C3G-BP complexes for treating UC and help develop better processing methods.


Assuntos
Mirtilos Azuis (Planta) , Colite Ulcerativa , Microbioma Gastrointestinal , Animais , Antocianinas , Anti-Inflamatórios/uso terapêutico , Caspase 3/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Pressão Hidrostática , Camundongos , Pectinas/metabolismo , Sulfatos
15.
Int J Biol Sci ; 18(4): 1381-1397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280677

RESUMO

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/ß-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/ß-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.


Assuntos
Berberina , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Berberina/efeitos adversos , Berberina/farmacologia , Berberina/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Proteômica , Via de Sinalização Wnt , beta Catenina/metabolismo
16.
Int J Biol Sci ; 18(4): 1737-1754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280696

RESUMO

Atrial Natriuretic Peptide (ANP) has known anti-inflammatory effects. However, the role of ANP in Ulcerative colitis (UC) remains unclear. This study aimed to explore the expression and function of ANP in UC, and its potential regulatory role in the stimulator of interferon genes (STING) pathway. Human colon biopsy and serum samples were collected between September 2018 and December 2019 at Wuhan Union Hospital. Levels of ANP and its receptors and STING pathway components were detected in people with UC and mice with dextran sulfate sodium (DSS)-induced colitis. These mice and HT-29 cells were treated with ANP and an agonist of the STING pathway. The level of inflammation, STING pathway, gut barrier, and endoplasmic reticulum (ER) stress-induced autophagy were measured. We found that the levels of ANP and its receptor decreased and the STING pathway activated statistically in people with UC and the mouse model of colitis. ANP treatment attenuated DSS-induced colitis and inhibited STING pathway phosphorylation in colonic tissue and epithelial cells. An interaction between cGAS and NPR-A was verified. ANP repaired the gut barrier and inhibited ER stress-induced autophagy via the STING pathway. ANP may thus alter colonic barrier function and regulate ER stress-induced autophagy as a promising therapy for UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Fator Natriurético Atrial , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Camundongos , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/farmacologia
17.
Food Funct ; 13(7): 4047-4060, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35315466

RESUMO

This study aimed to investigate the effects of long-term maternal intake of inulin on intestinal morphology, permeability, inflammation and microbiota of offspring rats treated with dextran sulfate sodium (DSS). Sixteen female adult Sprague-Dawley rats were assigned to two groups receiving the fiber-free diet (FFD) or inulin diet (INU, 5% inulin) for three parities. The offspring weaned rats (third-parity) were fed with the same diet for four weeks until receiving 6% DSS for 7 days; the four groups were as follows: FFD, FFD + DSS, INU and INU + DSS. The results showed that maternal intake of inulin increased the histopathology score and activity of diamine oxidase (DAO) in serum, and the highest histopathology scores and activity of DAO were observed in INU + DSS rats. Maternal intake of inulin increased the activity of myeloperoxidase (MPO), mRNA expressions of inflammatory factors and protein expression of IL-1ß in colonic tissues. Likewise, INU + DSS rats had the highest activity of MPO and mRNA expressions of inflammatory factors in colonic tissues. Maternal intake of inulin increased the abundances of Bacteroidetes, Bacteroides and Parasutterella, which were the highest enriched in INU + DSS rats. The level of acetate in the colonic digesta of INU + DSS rats was lower than that in FFD and INU rats. These results indicated that long-term maternal intake of inulin exacerbated the intestinal damage and inflammation of DSS-induced offspring rats, associated with the decreased level of acetate and altered intestinal microbiota.


Assuntos
Colite , Inulina , Animais , Colite/metabolismo , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Feminino , Inflamação/metabolismo , Intestinos , Inulina/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley
18.
Food Funct ; 13(6): 3732-3745, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35266931

RESUMO

Ulcerative colitis is a recurrent inflammatory illness of the colon with an elevated risk of developing colon cancer. The drugs presently used to treat UC cause adverse effects and are limited to symptomatic treatments. To overcome these constraints, naturally derived novel alternative therapies are being tested. Ensete superbum Roxb. Cheesman (wild banana) is used as a folk medicinal plant to treat stomach aches, diarrhea, and dysentery. Previous research has shown that a peel dioxane (PD) fraction obtained from a ripe peel aqueous extract of E. superbum Roxb. Cheesman possesses in vitro antioxidant, anti-inflammatory and anti-colon cancer effects. Furthermore, it has been shown to alleviate 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced ulcerative colitis (UC) in rats. The current study intended to evaluate its efficacy as a functional dietary component added to cold pressed orange juice in colitic rats, and deduce the molecular processes involved in UC amelioration. The PD fraction in orange juice ameliorated colitis by modulating the oxidative stress and inflammatory parameters in the damaged tissue with improved healing activity as indicated by a lower disease activity index (DAI) score. The ameliorative effect was related to the inhibition of the nuclear factor-κB (NF-κB) signaling pathway by downregulating the expression levels of NFκBp65, TNF-α, IL-6 and IL-1ß, followed by the recovery of epithelial barrier integrity. The ameliorating effects were statistically similar (p > 0.05) to those of the standard sulfasalazine treated population. The results suggest that PD fractions can be used as a new functional food and as an adjuvant to prevent IBDs due to their anti-colitic effect; however, it needs to be confirmed in clinical trials.


Assuntos
Colite Ulcerativa , Colite , Ingredientes de Alimentos , Animais , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/metabolismo , Modelos Animais de Doenças , Alimento Funcional , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Extratos Vegetais/metabolismo , Ratos , Ácido Trinitrobenzenossulfônico/efeitos adversos
19.
Eur J Pharm Biopharm ; 173: 92-102, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35227857

RESUMO

Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog. Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology. GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure. In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.


Assuntos
Intestino Delgado , Muco , Animais , Colo/metabolismo , Cães , Trato Gastrointestinal/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Muco/metabolismo , Estômago
20.
Gut Microbes ; 14(1): 2041943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35230892

RESUMO

Genetic defects in SLC26A3 (DRA), an intestinal Cl-/HCO3- exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. Slc26a3-/- mice serve as a model to understand the pathophysiology of CLD and search for treatment options. This study investigates the microbiota changes in slc26a3-/- colon, the genotype-related causes for the observed microbiota alterations, its inflammatory potential, as well as the corresponding host responses. The luminal and the mucosa-adherent cecal and colonic microbiota of cohoused slc26a3-/- and wt littermates were analyzed by 16S rRNA gene sequencing. Fecal microbiota transfer from cohoused slc26a3-/- and wt littermates to germ-free wt mice was performed to analyze the stability and the inflammatory potential of the communities.The cecal and colonic luminal and mucosa-adherent microbiota of slc26a3-/- mice was abnormal from an early age, with a loss of diversity, of short-chain fatty acid producers, and an increase of pathobionts. The transfer of slc26a3-/- microbiota did not result in intestinal inflammation and the microbial diversity in the recipient mice normalized over time. A strong increase in the expression of Il22, Reg3ß/γ, Relmß, and other proteins with antimicrobial functions was observed in slc26a3-/- colon from juvenile age, while the mucosal and systemic inflammatory signature was surprisingly mild. The dysbiotic microbiota, low mucosal pH, and mucus barrier defect in slc26a3-/- colon are accompanied by a stark upregulation of the expression of a panel of antimicrobial proteins. This may explain the low inflammatory burden in the gut of these mice.


Assuntos
Disbiose , Microbioma Gastrointestinal , Animais , Antiporters/genética , Colo/metabolismo , Disbiose/genética , Disbiose/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , RNA Ribossômico 16S/genética , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Regulação para Cima
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