RESUMO
Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.
Assuntos
Biomarcadores , Colite Ulcerativa , Poliaminas , Análise de Célula Única , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/terapia , Animais , Humanos , Camundongos , Biomarcadores/metabolismo , Análise de Célula Única/métodos , Poliaminas/metabolismo , Modelos Animais de Doenças , Proteína 2 Glutamina gama-Glutamiltransferase , Masculino , Feminino , Neoplasias Associadas a Colite/genética , Neoplasias Associadas a Colite/patologia , Neoplasias Associadas a Colite/metabolismo , Transglutaminases/genética , Transglutaminases/metabolismoRESUMO
Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.
Assuntos
Transplante de Microbiota Fecal , Lactobacillus , Humanos , Transplante de Microbiota Fecal/métodos , Adulto , Adolescente , Feminino , Masculino , Adulto Jovem , Método Duplo-Cego , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/microbiologia , Microbioma Gastrointestinal , Projetos Piloto , Fezes/microbiologia , Resultado do Tratamento , Doença de Crohn/terapia , Doença de Crohn/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologiaRESUMO
Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.
Assuntos
Bacteroides , Colite Ulcerativa , Transplante de Microbiota Fecal , Fezes , Mucosa Intestinal , Humanos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Masculino , Feminino , Fezes/microbiologia , Bacteroides/genética , Adulto , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Pessoa de Meia-Idade , Microbioma Gastrointestinal , Falha de Tratamento , RNA Ribossômico 16S/genética , MetabolomaRESUMO
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Half of the cases are associated with an immune dysfunction and are frequently triggered by pathergy such as a tissular aggression via surgery or burn wounds. A patient with ulcerative colitis presented a PG at the site of an iontophoresis patch for tendinopathy. Treatment in a specialized burn center, corticosteroid therapy and adapted local care contributed to a favourable evolution. PG remains a diagnosis of exclusion and inflammatory phenomena must be differentiated from infectious causes such as necrotizing fasciitis to initiate immunosuppressive treatment. Being rare and difficult to diagnose and to treat as well as associated with potentially severe sequelae, a multidisciplinary team is required for the management of PG.
Le Pyoderma gangrenosum (PG) est une dermatose neutrophilique rare. Il est, dans la moitié des cas, associé à une maladie dysimmunitaire et il est fréquemment déclenché par un phénomène de pathergie, défini comme une agression tissulaire par une intervention chirurgicale ou encore une brûlure. Une patiente avec une rectocolite ulcéro-hémorragique a développé un PG sur le site d'application d'un patch d'ionophorèse pour une tendinopathie. Un traitement par une corticothérapie, un traitement immunosuppresseur local et des soins locaux adaptés ont permis une évolution favorable. Le PG reste un diagnostic d'exclusion et les phénomènes inflammatoires doivent être différenciés de phénomènes infectieux, comme la fasciite nécrosante, afin d'initier rapidement des immunosuppresseurs. Comme il s'agit d'une pathologie rare avec un diagnostic difficile, que des séquelles peuvent être catastrophiques et qu'un traitement immunosuppresseur complexe doit être instauré, une équipe pluridisciplinaire est requise pour la prise en charge de cette pathologie.
Assuntos
Tratamento Conservador , Pioderma Gangrenoso , Humanos , Pioderma Gangrenoso/etiologia , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/terapia , Colite Ulcerativa/complicações , Colite Ulcerativa/terapia , Feminino , Pessoa de Meia-Idade , Tendinopatia/terapia , Tendinopatia/etiologia , Tendinopatia/diagnóstico , MasculinoRESUMO
Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.
Assuntos
Colite Ulcerativa , Modelos Animais de Doenças , Exossomos , Folículo Piloso , Células-Tronco Mesenquimais , Mitofagia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Colite Ulcerativa/metabolismo , Colite Ulcerativa/terapia , Colite Ulcerativa/patologia , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Folículo Piloso/metabolismo , Sulfato de Dextrana , Masculino , Mitocôndrias/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , HumanosRESUMO
Background: Accumulating evidence reveals mitochondrial dysfunction exacerbates intestinal barrier dysfunction and inflammation. Despite the growing knowledge of mitochondrial dysfunction and ulcerative colitis (UC), the mechanism of mitochondrial dysfunction in UC remains to be fully explored. Methods: We integrated 1137 UC colon mucosal samples from 12 multicenter cohorts worldwide to create a normalized compendium. Differentially expressed mitochondria-related genes (DE-MiRGs) in individuals with UC were identified using the "Limma" R package. Unsupervised consensus clustering was utilized to determine the intrinsic subtypes of UC driven by DE-MiRGs. Weighted gene co-expression network analysis was employed to investigate module genes related to UC. Four machine learning algorithms were utilized for screening DE-MiRGs in UC and construct MiRGs diagnostic models. The models were developed utilizing the over-sampled training cohort, followed by validation in both the internal test cohort and the external validation cohort. Immune cell infiltration was assessed using the Xcell and CIBERSORT algorithms, while potential biological mechanisms were explored through GSVA and GSEA algorithms. Hub genes were selected using the PPI network. Results: The study identified 108 DE-MiRGs in the colonic mucosa of patients with UC compared to healthy controls, showing significant enrichment in pathways associated with mitochondrial metabolism and inflammation. The MiRGs diagnostic models for UC were constructed based on 17 signature genes identified through various machine learning algorithms, demonstrated excellent predictive capabilities. Utilizing the identified DE-MiRGs from the normalized compendium, 941 patients with UC were stratified into three subtypes characterized by distinct cellular and molecular profiles. Specifically, the metabolic subtype demonstrated enrichment in epithelial cells, the immune-inflamed subtype displayed high enrichment in antigen-presenting cells and pathways related to pro-inflammatory activation, and the transitional subtype exhibited moderate activation across all signaling pathways. Importantly, the immune-inflamed subtype exhibited a stronger correlation with superior response to four biologics: infliximab, ustekinumab, vedolizumab, and golimumab compared to the metabolic subtype. Conclusion: This analysis unveils the interplay between mitochondrial dysfunction and the immune microenvironment in UC, thereby offering novel perspectives on the potential pathogenesis of UC and precision treatment of UC patients, and identifying new therapeutic targets.
Assuntos
Colite Ulcerativa , Mitocôndrias , Humanos , Colite Ulcerativa/imunologia , Colite Ulcerativa/terapia , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Mitocôndrias/metabolismo , Mitocôndrias/imunologia , Medicina de Precisão , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Aprendizado de Máquina , MasculinoRESUMO
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.
Assuntos
Biomarcadores , Exercício Físico , Fibronectinas , Qualidade de Vida , Humanos , Fibronectinas/sangue , Exercício Físico/fisiologia , Biomarcadores/sangue , Mucosa Intestinal/patologia , Animais , Doenças Inflamatórias Intestinais/sangue , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Microbioma Gastrointestinal , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Colite Ulcerativa/terapia , MiocinasRESUMO
OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.
Assuntos
Idade de Início , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , Adolescente , Criança , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Seguimentos , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Doença de Crohn/genética , Doença de Crohn/cirurgia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Colite Ulcerativa/genética , Colite Ulcerativa/cirurgia , Colite Ulcerativa/epidemiologiaRESUMO
Quality of life (QoL) in patients with inflammatory bowel disease (IBD) is influenced by several factors, many of which may also impact cognitive function. However, the extent of the interaction among these factors, QoL, and disease outcomes in IBD patients remains unknown. We thus aim to characterize the relationships among psychological disorders, coping mechanisms, cognitive function, and the overall impact on QoL and disease outcomes in patients with IBD. This cross-sectional observational study was conducted at an academic care center. QoL was evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and disease severity was evaluated using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). We also used the Hospital Anxiety and Depression scale (HADS). Regression models were used to test the associations among QoL, number of hospitalizations, disease severity, cognitive functioning (working memory [WM] and reaction time), and coping strategies while controlling for anxiety and depressive symptoms, age, and sex. This study included 41 patients (24 patients with CD and 17 with UC) whose mean age was 28.2 (±8.4) years (23 males) and mean SIBDQ score was 51.5 (±10.0). Patients with more WM errors had lower QoL scores (Pâ =â .041), whereas patients with higher anxiety levels had lower QoL and more active UC (Pâ =â .008 and Pâ =â .016, respectively). The use of avoidant coping mechanisms was associated with a significantly higher number of hospitalizations (Pâ =â .038), and patients who adopted more emotion-focused coping strategies had a longer illness duration (Pâ =â .021). Finally, patients with higher education levels were found to use more active coping mechanisms than others. These results confirm the impact of cognitive, psychological, and coping factors on QoL and disease outcomes in patients with IBD; however, the mechanisms by which these factors interrelate remain unclear. Therapies aimed at improving both cognitive functions and psychological conditions may thus be effective at improving QoL and disease outcomes in IBD patients, and education may play a positive role in promoting the adoption of more effective coping strategies among IBD patients.
Assuntos
Adaptação Psicológica , Cognição , Doenças Inflamatórias Intestinais , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Masculino , Feminino , Estudos Transversais , Adulto , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/complicações , Índice de Gravidade de Doença , Colite Ulcerativa/psicologia , Colite Ulcerativa/terapia , Doença de Crohn/psicologia , Doença de Crohn/complicações , Doença de Crohn/terapia , Adulto Jovem , Depressão/psicologia , Depressão/etiologia , Inquéritos e Questionários , Transtornos Mentais/psicologia , Ansiedade/psicologia , Ansiedade/etiologia , Capacidades de EnfrentamentoRESUMO
Inflammatory bowel diseases (IBD) are chronic, incurable inflammatory condition of the gut. They comprise Crohn's disease and ulcerative colitis. Crohn's disease (CD) may affect any tract of the gastrointestinal (GI) tract and is a transmural inflammatory condition; ulcerative colitis (UC), on the other hand, is limited to the mucosal layer of the rectum and colon. Treatment options available for both IBD are notoriously loaded with potentially serious side effects and risks. Although the pathogenesis of IBD involves a complex interaction between genetic, environmental, microbial and immunological factors, there is evidence that the interplay between the microbiota and the GI mucosa has a preponderant role. It is therefore no surprise that in recent years, a growing interest for effective and safer alternatives has focused on the potential role of prebiotics and-especially-probiotics.The mechanisms of action underlying the potential benefits of probiotics in IBD have been largely and quite extensively investigated in vitro and in vivo experiments. In terms of clinical evidence, the results of trials in the induction of remission of active CD or the maintenance of its remission with probiotics have been so far largely disappointing, to the point that their use in this disease cannot be at present recommended.On the contrary, for the treatment as well as for maintenance therapy of UC, there is clinical evidence of efficacy for some specific strains or multi-strain preparations.It is evident that this is a rapidly evolving and promising field; more data are very likely to yield a better understanding on what strains and in what doses should be used in different specific clinical settings, as we expect new and exciting developments of precision and even personalized therapy by the fast-growing field of probiogenomics.
Assuntos
Colite Ulcerativa , Probióticos , Humanos , Probióticos/uso terapêutico , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/microbiologia , Doença de Crohn/terapia , Doença de Crohn/microbiologia , Doença de Crohn/imunologia , Microbioma Gastrointestinal , Animais , Resultado do TratamentoRESUMO
Inflammatory bowel disease (IBD), a complex chronic inflammatory bowel disorder that includes Crohn's disease (CD) and Ulcerative Colitis (UC), has become a globally increasing health concern. Nutrition, as an important factor influencing the occurrence and development of IBD, has attracted more and more attention. As the most important nutrient, protein can not only provide energy and nutrition required by patients, but also help repair damaged intestinal tissue, enhance immunity, and thus alleviate inflammation. Numerous studies have shown that protein nutritional support plays a significant role in the treatment and remission of IBD. This article presents a comprehensive review of the pathogenesis of IBD and analyzes and summarizes the potential mechanisms of protein nutritional support in IBD. Additionally, it provides an overview of the clinical effects of protein nutritional support in IBD and its impact on clinical complications. Research findings reveal that protein nutritional support demonstrates significant benefits in improving clinical symptoms, reducing the risk of complications, and improving quality of life in IBD patients. Therefore, protein nutritional support is expected to provide a new approach for the treatment of IBD.
Assuntos
Proteínas Alimentares , Doenças Inflamatórias Intestinais , Apoio Nutricional , Humanos , Proteínas Alimentares/administração & dosagem , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/terapia , Apoio Nutricional/métodos , Qualidade de Vida , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Doença de Crohn/dietoterapia , Estado NutricionalRESUMO
Extracellular vesicles released by probiotics have been demonstrated to effectively alleviate intestinal inflammation, yet the precise underlying mechanisms remain unclear. In this research, for the first time, Lactobacillus plantarum UJS001 (LP-UJS) was isolated from fermented sauerkraut in Zhenjiang, China. Thereafter, the therapeutic effect of LP-UJS-derived extracellular vesicles (LP-UJS-EVs) on dextran sulfate sodium-induced ulcerative colitis (UC) in mice was analyzed to elucidate the immune mechanisms. According to our findings, LP-UJS-EVs played a pivotal role in restoring the intestinal barrier and alleviating intestinal inflammation. Notably, LP-UJS-EVs induced M2 polarization of macrophages, promoted the release of IL-10 and TGF-ß, inhibited the release of histamine, IL-6, and TNF-α, and exerted regulatory effects on intestinal microflora, as evidenced by the reduced abundances of Coprococcus, Parabacteroides, Staphylococcus, and Allobaculum, alongside the enhanced abundance of Prevotella. Furthermore, both LP-UJS and LP-UJS-EVs affected the lysine degradation pathway and significantly increased the abundance of related metabolites, especially oxoadipic acid. In summary, our results underscore the substantial therapeutic potential of LP-UJS and its secreted EVs in the treatment of UC.
Assuntos
Colite Ulcerativa , Vesículas Extracelulares , Microbioma Gastrointestinal , Lactobacillus plantarum , Macrófagos , Camundongos Endogâmicos C57BL , Probióticos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/imunologia , Lactobacillus plantarum/metabolismo , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/química , Macrófagos/imunologia , Macrófagos/metabolismo , Probióticos/farmacologia , Probióticos/administração & dosagem , Masculino , Humanos , Homeostase , Interleucina-10/metabolismo , Interleucina-10/genética , Interleucina-10/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/genética , Sulfato de Dextrana/efeitos adversos , Fator de Crescimento Transformador beta/metabolismoRESUMO
Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal inflammation and damaged mucosal barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, and intestinal microecological imbalance. Oral probiotics are a living therapy for intestinal diseases, but their clinical application is hindered by poor bacterial biological activity and insufficient intestinal retention. Here, we developed a targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core and modified melanin nanoparticles (MNPs) on its surface through a click reaction of tricarboxyphenylboronic acid for synergistic therapy of UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, and inhibited apoptosis but also significantly enhanced the viability of Lf probiotics in simulated gastrointestinal fluid. Fluorescence imaging in vivo revealed the high accumulation of Lf@MPB at the site of intestinal inflammation in dextran sulfate sodium-induced UC mice. Moreover, in vivo results demonstrated that Lf@MPB effectively alleviated oxidative stress and inflammatory response and restored the intestinal barrier. In addition, 16S rRNA gene sequencing verified that Lf@MPB could increase the abundance and diversity of intestinal microbial communities and optimize microbial composition to inhibit the progression of UC. This work combines effective antioxidant and anti-inflammatory strategies with the oral administration of functionalized probiotics to provide a promising alternative for UC treatment.
Assuntos
Colite Ulcerativa , Melaninas , Nanopartículas , Probióticos , Animais , Humanos , Masculino , Camundongos , Colite Ulcerativa/terapia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Sulfato de Dextrana , Microbioma Gastrointestinal/efeitos dos fármacos , Limosilactobacillus fermentum , Melaninas/química , Camundongos Endogâmicos C57BL , Nanopartículas/química , Probióticos/química , Probióticos/farmacologiaRESUMO
The nutritional status in inflammatory bowel disease (IBD) is often impaired, and adherence to the Mediterranean diet (MedDiet) remains under-investigated. The aim of this study was to assess diet quality (DQ) and adherence to MedDiet in a cohort of Sardinian IBD patients. We conducted a case-control study in which 50 Crohn's disease (CD) and 50 ulcerative colitis (UC) patients were matched with 100 healthy controls each. The Diet Quality Index (DQI-I) and Medi-Lite were used to assess DQ and adherence to MedDiet, respectively. Subgroup analysis by disease characteristics and use of advanced therapies were also carried out. DQI-I scored significantly lower in IBD, independently of disease localization and behavior (CD) and disease extent (UC): [DQI-I: CD 34.5 (IQR 33-37) vs. CTRL 40 (IQR 38.5-43) p < 0.0001; UC 34.5 (IQR 33-37) vs. CTRL 42 (IQR 40-44) p < 0.0001]. Medi-Lite scores were significantly lower in stricturing and ileo-colonic CD and in extensive UC: [Medi-Lite CD 7.5 (IQR 7-9)] vs. CTRL 9 (IQR 7-10) p = 0.0379]; [UC 8 (IQR7-10) vs. CTRL 9 (IQR 8-10.5) p = 0.0046]. IBD patients had a low DQ independently of disease type and phenotype. Patients with ileo-colonic stenosing CD or extensive UC had lower MedDiet adherence, suggesting that its benefits may be mitigated by low acceptance in specific subgroups.
Assuntos
Colite Ulcerativa , Doença de Crohn , Dieta Mediterrânea , Cooperação do Paciente , Humanos , Feminino , Estudos de Casos e Controles , Masculino , Adulto , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Doença de Crohn/dietoterapia , Colite Ulcerativa/dietoterapia , Colite Ulcerativa/terapia , Doenças Inflamatórias Intestinais/dietoterapia , Estado Nutricional , ItáliaRESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) experience difficulties in daily life and demanding self-care needs. The goal of our support for patients is to ease their difficulties and improve their belief in their capacity to self-manage their disease (self-efficacy), by increasing their ability for self-care. The nurse's contribution is vital in empowering patients and supporting them to better manage their disease. There is evidence that higher nurse staffing levels are associated with better patient outcomes in acute care settings, but little is known about the outpatient setting. The objective of this study was to explore the impact of multidisciplinary team care with abundant nurse staffing levels on patient-reported outcome measures (PROMs) among patients with IBD, encompassing Crohn's disease (CD) and ulcerative colitis (UC), in clinical remission. METHODS: Patients with IBD in clinical remission were included because disease activity influences the patient's subjective evaluation. A total of 499 valid responses from two different sources were analyzed: 318 from a specialized IBD clinic with abundant nurse staffing and a multidisciplinary care team (UC: 83, CD: 235) and 181 from an online survey panel (UC: 109, CD: 72). The IBD Self-Efficacy Scale (IBD-SES) and the difficulty of life scale (DLS) were used as disease-specific PROMs. RESULTS: In two multiple regression models adjusted by background characteristics (age, sex, diagnosis [UC/CD], employment status, use of biologics, and disease duration) using the IBD-SES or DLS as a dependent variable, the responses from clinic patients showed a more favorable score (higher self-efficacy or lower difficulty) than the online responses. CONCLUSIONS: Multidisciplinary team care with abundant nurse staffing may improve self-efficacy and ease difficulties of life among patients with IBD in clinical remission. These results could help bring attention to nurse staffing in an outpatient setting, which has previously been overlooked, and be the first to provide evidence of its importance in encouraging enhanced staffing levels.
Assuntos
Doenças Inflamatórias Intestinais , Equipe de Assistência ao Paciente , Medidas de Resultados Relatados pelo Paciente , Humanos , Feminino , Masculino , Adulto , Equipe de Assistência ao Paciente/organização & administração , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/enfermagem , Inquéritos e Questionários , Autoeficácia , Qualidade de Vida , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Doença de Crohn/psicologia , Admissão e Escalonamento de PessoalRESUMO
BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.
Assuntos
Colite Ulcerativa , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Sideróforos , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/genética , Masculino , Feminino , Fezes/microbiologia , Adulto , Pessoa de Meia-Idade , Microbioma Gastrointestinal/genética , Sideróforos/metabolismo , Resultado do Tratamento , Bactérias/genética , Genes Bacterianos , Dosagem de Genes , Curva ROCRESUMO
INTRODUCTION: Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue. STUDY OBJECTIVE: To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD. METHODS: Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared. RESULTS: One hundred patients were included (81 with Crohn's Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03). CONCLUSION: Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome.
Assuntos
Doença de Crohn , Complicações na Gravidez , Resultado da Gravidez , Humanos , Feminino , Gravidez , Adulto , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Nascimento Prematuro/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , França/epidemiologia , Recém-Nascido , Estudos Retrospectivos , Adulto Jovem , Cesárea/estatística & dados numéricosRESUMO
BACKGROUND: Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. OBJECTIVE: To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. METHODS: Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3 months later in children with IBD. RESULTS: In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3 years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p < 0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p < 0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p = 0.001) and UC (p = 0.012) compared with controls and decreased following treatment in UC (p = 0.01). In CD, propan-1-ol was significantly greater than controls (p < 0.001) and extensive colitis (p = 0.001) and fell with treatment (p = 0.05). Phenol was significantly greater in CD (p < 0.001) and fell with treatment in both CD (p = 0.02) and UC (p = 0.01). CONCLUSION: Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.
Assuntos
Colite Ulcerativa , Doença de Crohn , Fezes , Índice de Gravidade de Doença , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Feminino , Fezes/química , Fezes/microbiologia , Masculino , Criança , Estudos de Casos e Controles , Adolescente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/terapia , Cromatografia Gasosa-Espectrometria de Massas , Resultado do Tratamento , Reino Unido , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
INTRODUCTION: Approximately 20-30% of the patients with ulcerative colitis (UC) may present with isolated proctitis. Ulcerative proctitis (UP) is a challenging condition to manage due to its significant burden in terms of disabling symptoms. AREAS COVERED: PubMed was searched up to March 2024 to identify relevant studies on UP. A comprehensive summary and critical appraisal of the available data on UP are provided, highlighting emerging treatments and areas for future research. EXPERT OPINION: Patients with UP are often undertreated, and the disease burden is often underestimated in clinical practice. Treat-to-target management algorithms can be applied to UP, aiming for clinical remission in the short term, and endoscopic remission and maintenance of remission in the long term. During their disease, approximately one-third of UP patients require advanced therapies. Escalation to biologic therapy is required for refractory or steroid dependent UP. For optimal patient care and management of UP, it is necessary to include these patients in future randomized clinical trials.