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1.
World J Gastroenterol ; 30(12): 1644-1650, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38617734

RESUMO

In this editorial, we comment on the article by Marangoni et al, published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way. Furthermore, we provided dietary recommendations for patients with IBD. The Western diet, characterized by a low fiber content and deficiency the micronutrients, impacts short-chain fatty acids production and may be related to the pathogenesis of IBD. On the other hand, the consumption of the Mediterranean diet and dietary fibers are associated with reduced risk of IBD flares, particularly in Crohn's disease (CD) patients. According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the regular consumption of fruits and vegetables while reducing the consumption of saturated, trans, dairy fat, additives, processed foods rich in maltodextrins, and artificial sweeteners containing sucralose or saccharine is recommended to CD patients. For patients with ulcerative colitis, the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients, with the possible inclusion of red meats. In conclusion, IBD is a complex and heterogeneous disease, and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.


Assuntos
Colite Ulcerativa , Doença de Crohn , Dieta Mediterrânea , Doenças Inflamatórias Intestinais , MicroRNAs , Humanos , Doenças Inflamatórias Intestinais/genética , Doença de Crohn/genética
2.
BMC Public Health ; 24(1): 1038, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622673

RESUMO

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. RESULTS: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70-17.3). Breastfeeding (OR = 0.18, 95% CI 0.08-0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21-0.89) were negatively associated with CD. CONCLUSIONS: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Gravidez , Criança , Feminino , Humanos , Coorte de Nascimento , Finlândia/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Fatores de Risco , Ferro
3.
Phytomedicine ; 127: 155474, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471369

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestine, which significantly affects patients' quality of life. As a perennial plant with the homology of medicine and food, Panax ginseng is known for its substantial anti-inflammatory effects in various inflammatory disorders. Ginsenosides, the main bioactive compounds of P. ginseng, are recognized for their efficacy in ameliorating inflammation. PURPOSE: Over the past decade, approximately 150 studies have investigated the effects of P. ginseng and ginsenosides on IBD treatment and new issues have arisen. However, there has yet to be a comprehensive review assessing the potential roles of ginsenosides in IBD therapy. METHOD: This manuscript strictly adheres to the PRISMA guidelines, thereby guaranteeing systematic synthesis of data. The research articles referenced were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "ginsenoside", "IBD", "colitis", "UC", "inflammation", "gut microbiota", and "intestinal barrier". For image creation, Figdraw 2.0 was methodically employed. RESULTS: Treatment with various ginsenosides markedly alleviated clinical IBD symptoms. These compounds have been observed to restore intestinal epithelia, modulate cellular immunity, regulate gut microbiota, and suppress inflammatory signaling pathways. CONCLUSION: An increasing body of research supports the potential of ginsenosides in treating IBD. Ginsenosides have emerged as promising therapeutic agents for IBD, attributed to their remarkable efficacy, safety, and absence of side effects. Nevertheless, their limited bioavailability presents a substantial challenge. Thus, efforts to enhance the bioavailability of ginsenosides represent a crucial and promising direction for future IBD research.


Assuntos
Ginsenosídeos , Doenças Inflamatórias Intestinais , Panax , Humanos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Qualidade de Vida , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação/tratamento farmacológico
4.
PLoS One ; 19(3): e0299687, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512973

RESUMO

Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Physalis , Ribes , Ratos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Ésteres/metabolismo , Sacarose/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Citocinas/metabolismo , Colo/patologia , Doenças Inflamatórias Intestinais/patologia , Ácido Trinitrobenzenossulfônico/toxicidade
5.
Eur J Gastroenterol Hepatol ; 36(5): 563-570, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38477856

RESUMO

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.


Assuntos
Anemia Ferropriva , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adulto , Humanos , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Ferro/uso terapêutico , Progressão da Doença , Suplementos Nutricionais
6.
Zhen Ci Yan Jiu ; 49(3): 315-323, 2024 Mar 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500330

RESUMO

OBJECTIVES: To analyze the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of inflammatory bowel disease (IBD) based on complex network technology and provide the reliable evidences for acupoint selection in treatment of this disease with acupuncture and moxibustion. METHODS: The clinical studies on acupuncture-moxibustion treatment of IBD were searched from the databases including CNKI, Wanfang, VIP, PubMed and Embase. The studies were screened and the acupoint prescriptions were extracted to set up the database of acupuncture-moxibustion treatment for IBD. Using Microsoft Excel 2021 software, the use times of acupoint, the use frequency (%) of acupoint, meridian tropism and the use of special point were imported. With SPSS Modeler 18.0 software adopted, the association rules were analyzed on the acupoint prescriptions. The acupoint co-occurrence network diagram, k-core network diagram, and community analysis diagram were drawn by Gephi 0.9.5 software. RESULTS: A total of 156 studies were included, composed of 175 acupoint prescriptions, 75 acupoints, with 1 378 use times in total and around 8 acupoints in one prescription. Regarding the top use frequency, Tianshu (ST25), Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12) and Pishu (BL20) were listed. The top meridians involved were the foot-yangming stomach meridian, the foot-taiyang bladder meridian and the Conception Vessel. The front-mu point had been used with the highest frequency among the special points. ST36 and ST25 were a pair of points with the highest frequency in treatment. The k-core hierarchical analysis was adopted to optimize acupoint prescriptions, and 22 core acupoints were obtained, i.e. ST25, ST36, CV4, CV12, BL20, Dachangshu (BL25), Shangjuxu (ST37), Shenshu (BL23), Qihai (CV6), Sanyinjiao (SP6), Mingmen (GV4), Xingjian (LR2), Yinlingquan (SP9), Neiting (ST44), Taichong (LR3), Xiajuxu (ST39), Shuifen (CV9), Shenque (CV8), Ganshu (BL18), Weishu (BL21), Hegu (LI4) and Quchi(LI11), which were classified into three core acupoint groups by community analysis. CONCLUSIONS: Through complex network analysis, it is found that the local acupoints on the chest and abdomen are generally selected in treatment with acupuncture-moxibustion for IBD, the combination of the nearby and distal points is considered simulta-neously, and the acupoint prescription is modified according to syndrome/pattern differentiation;and among special points, the front-mu point is widely used in treatment. All of these rules provide the ideas for the acupoint selection of acupuncture-moxibustion in treatment of IBD.


Assuntos
Terapia por Acupuntura , Doenças Inflamatórias Intestinais , Meridianos , Moxibustão , Humanos , Pontos de Acupuntura , Doenças Inflamatórias Intestinais/terapia
7.
J Ethnopharmacol ; 328: 118025, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38458342

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.


Assuntos
Dinitrofluorbenzeno/análogos & derivados , Doenças Inflamatórias Intestinais , Extratos Vegetais , Camundongos , Animais , Extratos Vegetais/efeitos adversos , Commiphora , Interleucina-17 , Fator de Necrose Tumoral alfa , NF-kappa B , Interleucina-6 , Lipopolissacarídeos/farmacologia , Ciclo-Oxigenase 2 , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico
8.
Phytomedicine ; 128: 155408, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503153

RESUMO

BACKGROUND: Epigallocatechin-3-gallate (EGCG), the primary active compound in green tea, is recognized for its significant anti-inflammatory properties and potential pharmacological effects on inflammatory bowel disease (IBD). However, comprehensive preclinical evidence supporting the use of EGCG in treating IBD is currently insufficient. PURPOSE: To evaluate the efficacy of EGCG in animal models of IBD and explore potential underlying mechanisms, serving as a groundwork for future clinical investigations. METHODS: A systematic review of pertinent preclinical studies published until September 1, 2023, in databases such as PubMed, Embase, Web of Science, and Cochrane Library was conducted, adhering to stringent quality criteria. The potential mechanisms via which EGCG may address IBD were summarized. STATA v16.0 was used to perform a meta-analysis to assess IBD pathology, inflammation, and indicators of oxidative stress. Additionally, dose-response analysis and machine learning models were utilized to evaluate the dose-effect relationship and determine the optimal dosage of EGCG for IBD treatment. RESULTS: The analysis included 19 studies involving 309 animals. The findings suggest that EGCG can ameliorate IBD-related pathology in animals, with a reduction in inflammatory and oxidative stress indicators. These effects were observed through significant changes in histological scores, Disease Activity Index, Colitis Macroscopic Damage Index and colon length; a decrease in markers such as interleukin (IL)-1ß, IL-6 and interferon-γ; and alterations in malondialdehyde, superoxide dismutase, glutathione, and catalase levels. Subgroup analysis indicated that the oral administration route of EGCG exhibited superior efficacy over other administration routes. Dose-response analysis and machine learning outcomes highlighted an optimal EGCG dosage range of 32-62 mg/kg/day, with an intervention duration of 4.8-13.6 days. CONCLUSIONS: EGCG exhibits positive effects on IBD, particularly when administered at the dose range of 32 - 62 mg/kg/day, primarily attributed to its ability to regulate inflammation and oxidative stress levels.


Assuntos
Anti-Inflamatórios , Catequina , Catequina/análogos & derivados , Doenças Inflamatórias Intestinais , Estresse Oxidativo , Catequina/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Chá/química , Relação Dose-Resposta a Droga
9.
Phytomedicine ; 128: 155378, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38507851

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.


Assuntos
Cichorium intybus , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Hidroxibenzoatos , Raízes de Plantas , Transdução de Sinais , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Cichorium intybus/química , Transdução de Sinais/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Colite/tratamento farmacológico , Colite/induzido quimicamente , Raízes de Plantas/química , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Colo/efeitos dos fármacos , Colo/metabolismo , Extratos Vegetais/farmacologia , Sulfassalazina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Canais de Cátion TRPV/metabolismo
10.
Health Expect ; 27(2): e14004, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38433003

RESUMO

INTRODUCTION: Involving people with lived experience is fundamental to healthcare development and delivery. This is especially true for inflammatory bowel disease (IBD) services, where holistic and personalised models of care are becoming increasingly important. There is, however, a significant lack of representation of underserved and diverse groups in IBD research, and there are significant barriers to healthcare access and utilisation among minority groups in IBD. IBD centres need to be aware of these experiences to address barriers via service changes, improve interactions with local communities and promote meaningful engagement for improved health outcomes. METHODS: A pragmatic community-based approach was taken to engage with leaders and members of underserved groups across 11 workshops representing Roma, Afro-Caribbean, people of African descent and the wider black, Asian and minority ethnic (BAME) communities, Muslim women, refugee community members, deprived areas of South Yorkshire, LGBTQ+ and deaf populations. Thematic analysis of field notes identified patterns of attention across the community groups and where improvements to services were most frequently suggested. RESULTS: Findings demonstrated several barriers experienced to healthcare access and utilisation, including language accessibility, staff attitudes and awareness, mental health and stigma, continuity of support, and practical factors such as ease of service use and safe spaces. These barriers acted as a lever to co-producing service changes that are responsive to the health and social care needs of these groups. CONCLUSIONS: Engaging with people from a range of communities is imperative for ensuring that service improvements in IBD are accessible and representative of individual needs and values. PATIENT OR PUBLIC CONTRIBUTION: Local community leaders and members of community groups actively participated in the co-design and development of improvements to the IBD service for a local hospital. Their contributions further informed a pilot process for quality improvement programmes in IBD centres.


Assuntos
Doenças Inflamatórias Intestinais , Populações Vulneráveis , Humanos , Feminino , Melhoria de Qualidade , Serviços de Saúde Comunitária , Serviços de Saúde , Doenças Inflamatórias Intestinais/terapia
11.
J Ethnopharmacol ; 326: 117995, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38428656

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration of IBD. Persistent histological inflammation is considered to be the driving factor of colitis carcinogenesis. Effective control of inflammation is helpful to prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), a traditional Chinese medicine (TCM) formula, is originated from the ancient prescription of TCM for treating colitis and colorectal cancer. AYD has demonstrated efficacy in treating IBD and potential anti-carcinogenic properties. AIM OF THE STUDY: This research aims to assess the therapeutic efficacy of AYD in ameliorating experimental colitis-related carcinogenesis induced by AOM/DSS. It further seeks to elucidate its potential mechanisms by integrating multiple omics sequencing approaches. MATERIALS AND METHODS: A rat model for colitis-related carcinogenesis was developed using azoxymethane (AOM)/dextran sulfate sodium (DSS). UPLC-MS identified AYD's chemical constituents. Rats were administered varying doses of AYD (18.37, 9.19 and 4.59 g/kg) orally for 53 days, with mesalazine as a positive control. The study evaluated anti-carcinogenic effects by examining adenoma number, adenoma load, abnormal crypt foci (ACF), histopathological damage, and tumor-related protein expression. Anti-inflammatory and reparative effects were assessed through body weight, disease activity index (DAI), colon length, spleen index, inflammatory cytokine levels, and tight junction protein expression. The effects on intestinal microbiota and host metabolism were explored through 16S rRNA sequencing, targeted short-chain fatty acid (SCFA) metabonomics, and non-targeted colon metabolomics. Potential AYD targets were identified through transcriptomic sequencing and validated by qRT-PCR and western blotting. RESULTS: AYD significantly reduced adenoma number, adenoma load, neoplasm-associated lesions, ACF, and tumor-related protein expression (e.g., p53, PCNA) in AOM/DSS-induced rats, thus impeding colitis-related carcinogenesis progression. AYD also alleviated histopathological damage and inflammation, promoting intestinal mucosal barrier repair. Furthermore, AYD modulated intestinal flora structure, enhanced SCFA production, and regulated colon metabolites. Transcriptomic sequencing revealed a significant impact on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Subsequent qRT-PCR and western blotting experiments indicated AYD's influence in up-regulating PPAR-γ and down-regulating PPAR-α, PPAR-ß/δ, and related proteins (thrombomodulin [Thbd], fatty acid binding protein 5 [Fabp5], stearoyl-CoA desaturase 2 [Scd2], phospholipid transfer protein [Pltp]). CONCLUSIONS: This study demonstrates AYD's ability to inhibit experimental colitis-related carcinogenesis induced by AOM/DSS. Its mechanism likely involves modulation of the PPAR signaling pathway, impacting intestinal microbiota and host metabolic equilibrium.


Assuntos
Adenoma , Colite , Neoplasias Colorretais , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Ratos , Animais , Camundongos , Receptores Ativados por Proliferador de Peroxissomo , RNA Ribossômico 16S , Cromatografia Líquida , Espectrometria de Massas em Tandem , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação/patologia , Transdução de Sinais , Carcinogênese , Azoximetano/toxicidade , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Homeostase , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo
12.
Inflammopharmacology ; 32(2): 1005-1015, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38512653

RESUMO

The gut and the brain communicate bidirectionally through the autonomic nervous system. The vagus nerve is a key component of this gut-brain axis, and has numerous properties such as anti-inflammatory, antinociceptive, anti-depressive effects. A perturbation of this gut-brain communication is involved in the pathogeny of functional digestive disorders, such as irritable bowel syndrome, and inflammatory bowel diseases. Stress plays a role in the pathogeny of these diseases, which are biopsychosocial models. There are presently unmet needs of pharmacological treatments of these chronic debilitating diseases. Treatments are not devoid of side effects, cost-effective, do not cure the diseases, can lose effects over time, thus explaining the poor satisfaction of patients, their lack of compliance, and their interest for non-drug therapies. The gut-brain axis can be targeted for therapeutic purposes in irritable bowel syndrome and inflammatory bowel disease through non-drug therapies, such as hypnosis and vagus nerve stimulation, opening up possibilities for responding to patient expectations.


Assuntos
Hipnose , Doenças Inflamatórias Intestinais , Síndrome do Intestino Irritável , Estimulação do Nervo Vago , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Encéfalo
13.
J Pediatr Gastroenterol Nutr ; 78(4): 862-870, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426724

RESUMO

OBJECTIVES: The impact of disease burden extends beyond pediatric inflammatory bowel disease (IBD) patients to include their parents. Previous studies, predating the biologic era, have highlighted parental concerns about potential side effects associated with IBD medications. However, there is a notable gap in the literature regarding parents' perceptions of clinical studies involving pediatric IBD patients. This study aims to explore the specific concerns troubling parents of children with IBD, identifying factors influencing these concerns, and assesses parental willingness to allow their child's participation in clinical studies. METHODS: Utilizing social media, we disseminated an anonymous questionnaire to parents of pediatric IBD patients. The questionnaire encompassed queries about parental willingness for their child to partake in clinical studies, aspects of the disease deemed bothersome, and the sense of coherence scale (SOC). RESULTS: Responses were obtained from 101 parents, with a mean age of 46.4, of whom 82.2% were female. Concerns about potential future side effects of their child's medications surpassed worries about disease symptoms (80.04% vs. 73.47%). Linear regression analysis revealed that parents with lower SOC scores, limited medical care accessibility, and a higher age of the child at diagnosis, exhibited heightened concerns about the future impact of the disease on their child (p = 0.016, 0.003, and 0.045, respectively). While a majority rejected participation in studies involving new medications (54.5%), there was greater agreement for studies on nutritional therapies (84.2%) and complementary medicine (91.1%). Classification tree analysis indicated that women were more inclined to permit their child's participation in studies focusing on complementary medicine (adjusted p = 0.002). CONCLUSION: Parents of IBD patients express greater apprehension about potential side effects from IBD medications and display reluctance toward their child participating in clinical studies related to medications.


Assuntos
Terapias Complementares , Doenças Inflamatórias Intestinais , Criança , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Pais , Inquéritos e Questionários , Efeitos Psicossociais da Doença
14.
Aliment Pharmacol Ther ; 59(9): 1082-1095, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429885

RESUMO

BACKGROUND: IBDBIO-ASSIST was a randomised controlled trial assessing the efficacy of care provided by IBD nurse specialists in Germany in improving health-related quality of life (QoL) in IBD patients on biologic therapy. AIM: To evaluate patient-related outcomes and economic consequences associated with integrating IBD nurses into usual care. METHODS: We randomly assigned 1086 patients with IBD on biologic therapy to a control group (CG) receiving usual care or an intervention group (IG) receiving additional care from an IBD nurse specialist. The primary outcome was disease-specific QoL (sIBDQ) assessed at 6, 12 and 18 months. RESULTS: At baseline, patients in both groups were highly satisfied with their treatment situation and had relatively high sIBDQ values (range: 1-7; CG: 5.12; IG: 4.92). In the intention-to-treat (ITT) analysis of the overall sample, there was no significant difference in sIBDQ between groups at the assessment time points. However, a per-protocol analysis of patients with impaired QoL at baseline (EQ-VAS < 75 [median]), showed improvement in sIBDQ over 6 months that became significant at month 12 and remained significant through month 18 (baseline: IG 4.24; CG 4.31; 18 months: IG 5.02; CG 4.76; p = 0.017). CONCLUSION: High baseline satisfaction of IBD patients with treatment and the relatively high baseline sIBDQ values may have contributed to the lack of significant difference in sIBDQ scores for the overall sample. However, patients with impaired QoL derived significant benefit from additional care provided by an IBD nurse specialist, leading to meaningful improvements in sIBDQ over the long term.


Assuntos
Doenças Inflamatórias Intestinais , Qualidade de Vida , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia Biológica , Alemanha
15.
Drug Res (Stuttg) ; 74(4): 149-155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467159

RESUMO

It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.


Assuntos
Ácido Ascórbico , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Vitamina D/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico
16.
Adv Nutr ; 15(4): 100200, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438107

RESUMO

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium.


Assuntos
Doenças Inflamatórias Intestinais , Ácidos Cetoglutáricos , Humanos , Ácidos Cetoglutáricos/farmacologia , Ácidos Cetoglutáricos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/prevenção & controle , Mucosa Intestinal
17.
JPEN J Parenter Enteral Nutr ; 48(3): 258-266, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38357793

RESUMO

Diet strongly shapes the gut microbiome and metabolome, which in turn influence intestinal inflammation in patients with inflammatory bowel disease (IBD). Separate from inflammation and malnutrition, diet's direct interactions with the gastrointestinal system can also provoke or attenuate a host of nonspecific gastrointestinal symptoms. Given these multifaceted effects of diet on inflammation and symptoms, nutrition has been investigated for its potential roles in the prevention and treatment of IBD. This review presents epidemiological, observational cohort, and clinical trial evidence that underlie our current understanding of nutrition for prevention and treatment of IBD.


Assuntos
Doenças Inflamatórias Intestinais , Desnutrição , Humanos , Doenças Inflamatórias Intestinais/terapia , Estado Nutricional , Dieta , Desnutrição/prevenção & controle , Desnutrição/diagnóstico , Inflamação/prevenção & controle
18.
Gut Microbes ; 16(1): 2316575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38381494

RESUMO

Intestinal microbiota dysbiosis and metabolic disruption are considered essential characteristics in inflammatory bowel disorders (IBD). Reasonable butyrate supplementation can help patients regulate intestinal flora structure and promote mucosal repair. Here, to restore microbiota homeostasis and butyrate levels in the patient's intestines, we modified the genome of Saccharomyces cerevisiae to produce butyrate. We precisely regulated the relevant metabolic pathways to enable the yeast to produce sufficient butyrate in the intestine with uneven oxygen distribution. A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients, and the strongest can reach 1.8 g/L title of butyrate. Next, this series of strains was used to co-cultivate with gut microbiota collected from patients with mild-to-moderate ulcerative colitis. After receiving treatment with engineered strains, the gut microbiota and the butyrate content have been regulated to varying degrees depending on the synthetic ability of the strain. The abundance of probiotics such as Bifidobacterium and Lactobacillus increased, while the abundance of harmful bacteria like Candidatus Bacilloplasma decreased. Meanwhile, the series of butyrate-producing yeast significantly improved trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by restoring butyrate content. Among the series of engineered yeasts, the strain with the second-highest butyrate synthesis ability showed the most significant regulatory and the best therapeutic effect on the gut microbiota from IBD patients and the colitis mouse model. This study confirmed the existence of a therapeutic window for IBD treatment by supplementing butyrate, and it is necessary to restore butyrate levels according to the actual situation of patients to restore intestinal flora.


Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Saccharomyces cerevisiae/genética , Butiratos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Disbiose , Suplementos Nutricionais
19.
J Pediatr Gastroenterol Nutr ; 78(2): 272-279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38327225

RESUMO

AIM: To investigate whether a structured yoga program improves health-related quality of life (HRQOL) and self-efficacy in pediatric patients receiving care for inflammatory bowel disease (IBD). METHODS: IBD patients who were 10-17 years old participated in a 12 week, in-person yoga intervention at two clinical sites. Outcomes were measured at time of consent (T0), start of yoga (T1), and completion of yoga (T2) and 3 months after yoga completion (T3) using the IMPACT-III, Pediatric Quality of Life Inventory (PedsQL), and General Self Efficacy (GSE) scales. RESULTS: Seventy-eight patients were enrolled. Fifty-six patients completed nine or more classes. 73.2% had Crohn's disease and 26.8% ulcerative colitis or IBD-unclassified. A significant increase in IMPACT-III was seen from T1 to T3 (mean change of 5.22, SD = 14.33, p = 0.010), in the PedsQL (mean change = 2.3, SD = 10.24, p = 0.050), and GSE (mean change = 1, SD = 3.60, p = 0.046). 85.2% of patients reported yoga helped them to control stress. Long-term data was available for 47 subjects with 31.9% (n = 15) continuing to practice yoga one to 3 years after study completion. CONCLUSION: This structured 12-week yoga program showed significant improvements in HRQOL and general self-efficacy, particularly 3 months after classes were concluded suggesting that yoga's benefits may persist. Yoga is a safe and effective adjunct to standard medical care to improve QOL and self-efficacy in youth with IBD.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Yoga , Adolescente , Criança , Humanos , Colite Ulcerativa/terapia , Doenças Inflamatórias Intestinais/terapia , Estudos Prospectivos , Qualidade de Vida
20.
J Small Anim Pract ; 65(5): 317-328, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38354724

RESUMO

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.


Assuntos
Doenças do Cão , Deficiência de Vitamina B 12 , Vitamina B 12 , Animais , Cães , Feminino , Masculino , Administração Oral , Doença Crônica , Doenças do Cão/tratamento farmacológico , Doenças Inflamatórias Intestinais/veterinária , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Estudos Prospectivos , Enteropatias Perdedoras de Proteínas/veterinária , Enteropatias Perdedoras de Proteínas/tratamento farmacológico , Resultado do Tratamento , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêutico , Vitamina B 12/sangue , Deficiência de Vitamina B 12/veterinária , Deficiência de Vitamina B 12/tratamento farmacológico
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