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1.
Food Chem ; 462: 140951, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39213975

RESUMO

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.


Assuntos
Anti-Inflamatórios , Doenças Inflamatórias Intestinais , Polifenóis , Polissacarídeos , Polifenóis/química , Polifenóis/farmacologia , Polifenóis/administração & dosagem , Humanos , Polissacarídeos/química , Polissacarídeos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia
2.
Appl Microbiol Biotechnol ; 108(1): 463, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269473

RESUMO

The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.


Assuntos
Citocinas , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , RNA Ribossômico 16S , Transplante de Microbiota Fecal/métodos , Animais , Fezes/microbiologia , Camundongos , Humanos , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/microbiologia , Citocinas/metabolismo , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL , Sulfato de Dextrana , Masculino , Meios de Cultura/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação
3.
Int J Colorectal Dis ; 39(1): 140, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39266810

RESUMO

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.


Assuntos
Doenças Inflamatórias Intestinais , Transtornos do Sono-Vigília , Humanos , Masculino , Feminino , Fatores de Risco , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/complicações , Prevalência , Estudos Transversais , Adulto , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Análise Multivariada , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Qualidade do Sono
4.
Int J Mol Sci ; 25(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39273457

RESUMO

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.


Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Peixe-Zebra , Animais , Sulfato de Dextrana/efeitos adversos , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo
5.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273536

RESUMO

Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.


Assuntos
Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Metaboloma , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/genética , Disbiose/microbiologia , Animais
6.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39273567

RESUMO

Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium, Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.


Assuntos
Biomarcadores , Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Medicina de Precisão , Humanos , Disbiose/microbiologia , Criança , Feminino , Masculino , Doenças Inflamatórias Intestinais/microbiologia , Adolescente , Medicina de Precisão/métodos , RNA Ribossômico 16S/genética , Fezes/microbiologia , Pré-Escolar , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Íleo/microbiologia , Íleo/patologia , Colite Ulcerativa/microbiologia
7.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39273699

RESUMO

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein-protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics.


Assuntos
Biologia Computacional , Mapas de Interação de Proteínas , Humanos , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Transcriptoma , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Perfilação da Expressão Gênica , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Redes Reguladoras de Genes , Neutrófilos/imunologia , Neutrófilos/metabolismo , Transdução de Sinais/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , NADPH Oxidases
8.
Nutrients ; 16(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39275212

RESUMO

Microbial dysbiosis may manifest as inflammation both orally and in the gastrointestinal tract. Altered oral and gut microbiota composition and decreased diversity have been shown in inflammatory bowel disease (IBD) and periodontal disease (PD). Recent studies have verified transmission of oral opportunistic microbes to the gut. Prebiotics, probiotics, or dietary interventions are suggested to alleviate IBD symptoms in addition to medicinal treatment. Lingonberries contain multiple bioactive molecules, phenolics, which have a broad spectrum of effects, including antimicrobial, anti-inflammatory, antioxidant, anti-proteolytic, and anti-cancer properties. An all-natural product, fermented lingonberry juice (FLJ), is discussed as a potential natural anti-inflammatory substance. FLJ has been shown in clinical human trials to promote the growth of oral lactobacilli, and inhibit growth of the opportunistic oral pathogens Candida, Streptococcus mutans, and periodontopathogens, and decrease inflammation, oral destructive proteolysis (aMMP-8), and dental microbial plaque load. Lactobacilli are probiotic and considered also beneficial for gut health. Considering the positive outcome of these oral studies and the fact that FLJ may be swallowed safely, it might be beneficial also for the gut mucosa by balancing the microbiota and reducing proteolytic inflammation.


Assuntos
Anti-Inflamatórios , Sucos de Frutas e Vegetais , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Anti-Inflamatórios/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/dietoterapia , Fermentação , Vaccinium vitis-Idaea , Boca/microbiologia , Probióticos/administração & dosagem , Disbiose , Simbiose
9.
Nutrients ; 16(17)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39275270

RESUMO

BACKGROUND: Since diet is generally recognized as an important factor directly modulating the gut microbiome, it is also considered a potential environmental triggering factor for the pathogenesis and onset of inflammatory bowel disease (IBD). While the habitual and sex-related dietary behavior of the general population has been the subject of extensive study and reporting, data on IBD patients' dietary behavior and especially its sex-related differences are underrepresented. However, as diet is an important factor in the course of IBD, we hypothesized that men and women with IBD have a different dietary profile than the general population. METHODS: We performed a cohort analysis of a monocentric, cross-sectional study and compared the sex-related dietary behavior of 82 IBD patients (n = 40 women) to a sex- and age-matched cohort of the general German population [n = 328 (n = 160 women)]. Further on, disease-related quality of life and fecal calprotectin were correlated to the IBD patients' dietary behavior. RESULTS: While sex-related dietary behavior was frequently of statistical difference in the general population within the IBD cohort, only minor numerical differences were observed between the sexes, which were rarely statistically significant. However, correlation analyses of disease-related quality of life (IBDQ) and diet revealed significant differences in male IBD patients but not in female IBD patients (p = 0.007; r = 0.409 for energy intake (kJ/d); p = 0.003, r = 0.449 for adherence to Mediterranean diet). CONCLUSION: The dietary behavior of IBD patients showed more similarity between the sexes than the general German population. Distinct sex-related trends and differences in correlation with disease parameters demonstrated a significant difference for an adaptive dietary behavior, especially in IBD men.


Assuntos
Dieta , Fezes , Comportamento Alimentar , Doenças Inflamatórias Intestinais , Humanos , Feminino , Masculino , Adulto , Estudos Transversais , Doenças Inflamatórias Intestinais/psicologia , Comportamento Alimentar/psicologia , Pessoa de Meia-Idade , Fatores Sexuais , Dieta/estatística & dados numéricos , Fezes/química , Qualidade de Vida , Complexo Antígeno L1 Leucocitário/análise , Estudos de Coortes , Alemanha/epidemiologia , Idoso , Microbioma Gastrointestinal
10.
Nutrients ; 16(17)2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39275347

RESUMO

BACKGROUND/OBJECTIVES: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn's disease (CD). METHODS: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. RESULTS: In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. CONCLUSIONS: Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans.


Assuntos
Anti-Inflamatórios , Suplementos Nutricionais , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Permeabilidade , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/dietoterapia , Ileíte/tratamento farmacológico , Ileíte/prevenção & controle
11.
Pharmacol Res ; 208: 107403, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39265668

RESUMO

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic disorders characterized by dysregulated immune response and persistent inflammation. Recent studies suggest that bile acid receptors, particularly GPBAR1, and the transcription factor RORγt play critical roles in modulating intestinal inflammation. This study evaluates the therapeutic potential of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in IBD models. The effects of PBT002 were assessed through in vitro and in vivo experiments. Macrophages and T lymphocytes obtained from the buffy coat were exposed to PBT002 to evaluate its immunomodulatory activity. The beneficial effects in vivo were evaluated in mouse models of colitis induced by TNBS, DSS or DSS + IL-23 using also a Gpbar1 knock-out male mice. PBT002 exhibited an EC50 of 1.2 µM for GPBAR1 and an IC50 of 2.8 µM for RORγt. In in vitro, PBT002 modulated macrophage polarization towards an anti-inflammatory M2 phenotype and reduced Th17 cell markers while increasing Treg markers. In the TNBS-induced colitis model, PBT002 reduced weight loss, CDAI, and colon damage, while it modulated cytokine gene expression towards an anti-inflammatory profile. In GPBAR1-/-, the anti-inflammatory effects of PBT002 were attenuated, indicating partial GPBAR1 dependence. RNA sequencing revealed significant modulation of inflammatory pathways by PBT002. In DSS+IL-23 induced colitis, PBT002 mitigated disease exacerbation, reducing pro-inflammatory cytokine levels and immune cell infiltration. In conclusion, PBT002, a GPBAR1 agonist and RORγt inverse agonist, modulates both the innate and adaptive immune responses to reduce inflammation and disease severity in models of IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Macrófagos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Receptores Acoplados a Proteínas G , Animais , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Masculino , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Camundongos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Agonismo Inverso de Drogas , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças
12.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167489, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39233260

RESUMO

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disrupted immune function. Indeed, gut microbiota dysbiosis and metabolomic profile alterations, are hallmarks of IBD. In this scenario, metabolite-sensing G-protein coupled receptors (GPCRs), involved in several biological processes, have emerged as pivotal players in the pathophysiology of IBD. The aim of this study was to characterize the axis microbiota-metabolite-GPCR in intestinal surgical resections from IBD patients. Results showed that UC patients had a lower microbiota richness and bacterial load, with a higher proportion of the genus Cellulosimicrobium and a reduced proportion of Escherichia, whereas CD patients showed a decreased abundance of Enterococcus. Furthermore, metabolomic analysis revealed alterations in carboxylic acids, fatty acids, and amino acids in UC and CD samples. These patients also exhibited upregulated expression of most metabolite-sensing GPCRs analysed, which positively correlated with pro-inflammatory and pro-fibrotic markers. The role of GPR109A was studied in depth and increased expression of this receptor was detected in epithelial cells and cells from lamina propria, including CD68+ macrophages, in IBD patients. The treatment with ß-hydroxybutyrate increased gene expression of GPR109A, CD86, IL1B and NOS2 in U937-derived macrophages. Besides, when GPR109A was transiently silenced, the mRNA expression and secretion of IL-1ß, IL-6 and TNF-α were impaired in M1 macrophages. Finally, the secretome from siGPR109A M1 macrophages reduced the gene and protein expression of COL1A1 and COL3A1 in intestinal fibroblasts. A better understanding of metabolite-sensing GPCRs, such as GPR109A, could establish their potential as therapeutic targets for managing IBD.


Assuntos
Disbiose , Microbioma Gastrointestinal , Macrófagos , Receptores Acoplados a Proteínas G , Receptores Nicotínicos , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Disbiose/microbiologia , Disbiose/metabolismo , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Masculino , Macrófagos/metabolismo , Macrófagos/microbiologia , Feminino , Adulto , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Cadeia alfa 1 do Colágeno Tipo I , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Doença de Crohn/microbiologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia
13.
Ned Tijdschr Tandheelkd ; 131(9): 359-362, 2024 09.
Artigo em Holandês | MEDLINE | ID: mdl-39250685

RESUMO

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to bowel symptoms, patients may also have oral manifestations. This thesis investigated potential associations between disease activity in the gut, oral health, salivary gland function, and saliva composition. Patients with Crohn's disease had a significantly higher DMFT index, but showed no difference in periodontal diseases compared to a healthy control group. The saliva composition in patients with active bowel disease differed from that in patients with inactive bowel disease, suggesting that saliva analysis could potentially be used in the future to determine the degree and severity of bowel disease. The knowledge of gastroenterologists and dentists regarding oral manifestations of bowel diseases was found to be limited. Gastroenterologists and dentists valued interdisciplinary patient consultation as very useful, but the frequency of consultation was considered insufficient.


Assuntos
Saúde Bucal , Humanos , Saliva/química , Saliva/metabolismo , Doenças Inflamatórias Intestinais/complicações , Doença de Crohn/complicações , Doenças da Boca/etiologia , Doenças Periodontais/etiologia , Colite Ulcerativa/complicações , Glândulas Salivares
14.
Int J Biol Sci ; 20(12): 4618-4634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309424

RESUMO

Some colorectal cancer patients have experienced normal epithelial transformation into inflammatory and tumor states, but the molecular basis still needs to be further determined. The expression levels of SIX4 are gradually increased in dextran sodium sulfate (DSS) and azoxymethane (AOM)/DSS-induced colonic epithelial inflammation and tumors, respectively, in mice. Targeting SIX4 alleviates intestinal inflammation occurrence and reduces adenoma formation in mice. Clinical sample assays indicated that SIX4 is upregulated in inflammatory bowel disease (IBD) and colorectal cancer (CRC) tissues compared to normal colorectal tissues. In a subsequent study, we found that SIX4, transcriptionally activated by the proinflammatory IL-6/STAT3 signal, binds to c-Jun to transcribe IL-6, thus forming a positive IL-6/STAT3/SIX4/c-Jun feedback loop, which further induces intestinal inflammation occurrence. In addition, elevated SIX4 also induces the expression of DeltaNp63, rather than wild-type p63, by binding to its promoter and thus facilitates the activation of tumor stemness signals, which ultimately leads to the formation of colorectal cancer. Our study first observes that activated SIX4 in inflammation induction drives the transformation of colorectal epithelium into inflammation and tumor, which demonstrates SIX4 as a significant therapeutic target in IBD and colitis-associated colorectal cancer (CAC) and CRC pathogenesis.


Assuntos
Neoplasias Colorretais , Inflamação , Transdução de Sinais , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Camundongos , Inflamação/metabolismo , Humanos , Interleucina-6/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Sulfato de Dextrana , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/induzido quimicamente , Camundongos Endogâmicos C57BL , Mucosa Intestinal/metabolismo , Azoximetano
15.
Theranostics ; 14(14): 5643-5661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310109

RESUMO

Rationale: Inflammatory bowel disease (IBD) is a chronic disorder characterized by persistent inflammation of the gastrointestinal tract. Due to the elusive causes and complex mechanisms of this disorder, the development of highly effective therapeutic drugs is crucial. Extracellular vesicles (EVs) are small membrane-bound structures released by cells into the surrounding environment. Recent research has witnessed a substantial surge in the utilization of plant-derived EVs that offer advantages such as high productivity, low production costs, diverse biological functions, and low cytotoxicity. Herein, Red cabbage-derived EVs (Rabex) were investigated and engineered as potential therapeutic agents for IBD. Methods: Rabex was engineered by surface conjugation with hyaluronic acid (t-Rabex) to simultaneously enhance the targeting of intestinal epithelial and immune cells, thereby improving their therapeutic targeting and efficacy. The properties and therapeutic potential of t-Rabex were assessed through both in vitro studies and in vivo experiments, focusing on their capacity to reach the gastrointestinal tract and exert a therapeutic effect compared to unmodified Rabex. Results: Rabex exhibited dual functions, including the suppression of inflammation in macrophages and promotion of colon epithelial cell regeneration, both of which are critical for effective IBD treatment. In vitro and in vivo studies of t-Rabex have demonstrated its superior targeting efficiency to the gastrointestinal tract and therapeutic efficacy compared to Rabex, making it a promising and more effective IBD treatment. Understanding the mechanism of action of t-Rabex in colonic tissues highlighted its anti-inflammatory, antioxidative, and tight-junction maintenance properties. Conclusions: These findings underscore the potential of t-Rabex as a precise therapeutic agent for IBD and shed light on the diverse applications of plant-derived EVs.


Assuntos
Colite , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Animais , Camundongos , Colite/tratamento farmacológico , Humanos , Brassica , Doenças Inflamatórias Intestinais/terapia , Inflamação , Ácido Hialurônico/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Células RAW 264.7 , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos
16.
J Med Internet Res ; 26: e53512, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240663

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) poses significant challenges for patients, requiring continuous monitoring and self-management to improve quality of life. OBJECTIVE: This study aims to investigate the viewpoints of individuals living with IBD on the use of information and communication technology (ICT) for the self-management of their condition, with a particular focus on the concept of a "smart" toilet seat as an example of ICT for IBD self-management. METHODS: We conducted an analysis of questionnaire responses obtained from 724 participants. They were encouraged to share their use cases and identify any perceived barriers associated with ICT adoption for managing their condition. To assess their responses, we used descriptive quantitative analysis, summative content analysis, and thematic qualitative analysis. We combined these results in an epistemic network analysis to look for meaningful patterns in the responses. RESULTS: Of the 724 participants, more than half (n=405, 55.9%) were already using various forms of ICT for IBD self-management. The primary factor influencing their use of ICT was their affinity for interacting with technology. Distinct differences emerged between individuals who were using ICT and those who were not, particularly regarding their perceived use cases and concerns. CONCLUSIONS: This study provides valuable insights into the perspectives of individuals with IBD on the use of ICT for self-management. To facilitate wider adoption, addressing privacy concerns, ensuring data security, and establishing reliable ICT integration will be critical.


Assuntos
Doenças Inflamatórias Intestinais , Autogestão , Telemedicina , Humanos , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/psicologia , Autogestão/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem , Idoso , Qualidade de Vida
17.
Adv Immunol ; 163: 1-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39271257

RESUMO

Autophagy, a highly conserved catabolic process that targets various types of cellular cargoes to lysosomal degradation, is one of the most important biological mechanisms critical for cellular homeostasis. Components of these cellular cargoes can range from individual proteins to invading pathogens, and degrading these materials is important for maintaining organismal health and survival. The process of autophagy is carried out by complex molecular mechanisms, and a growing body of evidence indicates that these mechanisms intersect with those involved in the cell death pathways. In this review, we examine several emerging studies elucidating the role of autophagy in RIP1-mediated cell death signaling, with particular emphasis on impaired autophagy caused by ATG16L1 deficiency. We also discuss how autophagy in RIP1-mediated cell death affects intestinal homeostasis in preclinical models, and the implications of the intersection between RIP1 and autophagy for understanding the intestinal pathologies associated with inflammatory bowel disease (IBD). Finally, we highlight the potential benefits of therapeutic targeting of RIP1 and autophagy proteins, while also proposing areas of research that will likely elucidate new links between autophagy and cell death signaling.


Assuntos
Autofagia , Complexo de Proteínas Formadoras de Poros Nucleares , Proteínas de Ligação a RNA , Transdução de Sinais , Animais , Humanos , Morte Celular , Inflamação/imunologia , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/imunologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteínas de Ligação a RNA/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
18.
Front Immunol ; 15: 1403420, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229260

RESUMO

Background: Lymphocytes play a key role in the pathogenesis of inflammatory bowel disease (IBD) and are widely explored as promising prognostic indicators. We aimed to outline the existing evidences on the capability of lymphocyte subpopulations to predict disease progression and treatment response in patients with IBD. Methods: The protocol for this review was registered in PROSPERO (registration ID: CRD 42022364126). Systematic retrieval was conducted using PubMed, Embase, and Web of Science databases. Original articles on the prognostic value of lymphocyte subsets in IBD published up to April 8, 2023 were eligible for inclusion. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. Results: Twenty studies were ultimately included: eight evaluated the prediction of disease progression and 12 focused on the prediction of treatment response. According to the Newcastle-Ottawa Scale, three studies were of high quality, 16 were of moderate quality, and only one was of low quality. T-cell subpopulations, including CD4+ T cells, CD8+ T cells, and γδ T cells, are revealed to have prognostic capacity. Transmembrane tumor necrosis factor α-bearing lymphocytes, CD4+ T cells, CD8+ T cells, and Plasma cells are found to have the potential to predict the response to anti-TNFα agents. In contrast memory T cells, CD4+ T cells, and naïve B cells may predict the response to vedolizumab. Conclusions: This systematic review identified several potential lymphocyte subset-related predictors. If verified in large cohort prospective studies, these findings could aid clinical decision-making. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022364126.


Assuntos
Progressão da Doença , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/diagnóstico , Prognóstico , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Resultado do Tratamento , Anticorpos Monoclonais Humanizados
19.
Carbohydr Polym ; 346: 122647, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245532

RESUMO

Incorporating 5-aminosalicylic acid (5-ASA) into a colon-specific carrier is crucial for treating inflammatory bowel diseases (IBD), as it enhances therapeutic efficacy, targets the affected regions directly, and minimizes side effects. This study evaluated the impact of incorporating cellulose nanofibers (CNF) on the in vitro and in vivo biological performance of retrograded starch/pectin (RS/P) microparticles (MPs) containing 5-ASA. Using Fourier Transform Infrared (FTIR) Spectroscopy, shifts in the spectra of retrograded samples containing CNF were observed with increasing CNF proportions, suggesting the establishment of new supramolecular interactions. Liquid absorption exhibited pH-dependent behaviors, with reduced absorption in simulated gastric fluid (∼269 %) and increased absorption in simulated colonic fluid (∼662 %). Increasing CNF concentrations enhanced mucoadhesion in porcine colonic sections, with a maximum force of 3.4 N at 50 % CNF. Caco-2 cell viability tests showed biocompatibility across all tested concentrations (0.0625-2.0000 mg/mL). Evaluation of intestinal permeability in Caco-2 cell monolayers demonstrated up to a tenfold increase in 5-ASA permeation, ranging from 29 % to 48 %. An in vivo study using Galleria mellonella larvae, with inflammation induced by LPS, showed reduction of inflammation. Given the scalability of spray-drying, these findings suggest the potential of CNF-incorporated RS/P microparticles for targeted 5-ASA delivery in IBD.


Assuntos
Doenças Inflamatórias Intestinais , Mesalamina , Nanofibras , Pectinas , Amido , Mesalamina/química , Mesalamina/farmacologia , Mesalamina/administração & dosagem , Animais , Células CACO-2 , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Nanofibras/química , Nanofibras/toxicidade , Suínos , Pectinas/química , Amido/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem
20.
J Korean Acad Nurs ; 54(3): 386-402, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39248424

RESUMO

PURPOSE: The purpose of this study was to conduct a pre-conception care program for women of childbearing age with inflammatory bowel disease (IBD) in Korea and verify its effects on self-efficacy for IBD management, IBD-related pregnancy knowledge, and IBD-related pregnancy anxiety. It also aimed to explore the changes in participants through the program. METHODS: A convergent mixed-methods study design was adopted. In the quantitative phase, 35 women (17 and 18 in the intervention and control group, respectively) participated. The intervention group attended a program that included small-group sessions and individual tele-coaching. To confirm the effects, data were collected before and one and four weeks after the intervention. In the qualitative stage, focus group interviews and tele-coaching were conducted with the intervention group. RESULTS: After the program ended, significant differences were observed over time between the intervention and control groups for self-efficacy for IBD management (Wald χ² = 4.41, p = .036), IBD-related pregnancy knowledge (Wald χ² = 13.80, p < .001) and IBD-related pregnancy anxiety (Wald χ² = 8.61, p = .003). Qualitative data analysis revealed the following themes: (1) improving confidence in IBD management and awareness for planned pregnancy; (2) improving IBD awareness related to pregnancy and childbirth; and (3) relieving anxiety about and actively facing pregnancy. CONCLUSION: This study is meaningful in that, to the best of our knowledge, it is the first to develop a pre-conception care program for women diagnosed with IBD and confirm its effectiveness. Furthermore, this program is expected to be suitable for patient counseling and education in clinical practice.


Assuntos
Ansiedade , Grupos Focais , Doenças Inflamatórias Intestinais , Cuidado Pré-Concepcional , Avaliação de Programas e Projetos de Saúde , Autoeficácia , Humanos , Feminino , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/patologia , Adulto , Gravidez , Conhecimentos, Atitudes e Prática em Saúde , Entrevistas como Assunto , Adulto Jovem , Inquéritos e Questionários , Complicações na Gravidez/psicologia , Complicações na Gravidez/patologia , Educação de Pacientes como Assunto
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