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1.
Stud Health Technol Inform ; 285: 165-170, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34734869

RESUMO

In this study, we investigate faecal microbiota composition, in an attempt to evaluate performance of classification algorithms in identifying Inflammatory Bowel Disease (IBD) and its two types: Crohn's disease (CD) and ulcerative colitis (UC). From many investigated algorithms, a random forest (RF) classifier was selected for detailed evaluation in three-class (CD versus UC versus nonIBD) classification task and two binary (nonIBD versus IBD and CD versus UC) classification tasks. We dealt with class imbalance, performed extensive parameter search, dimensionality reduction and two-level classification. In three-class classification, our best model reaches F1 score of 91% in average, which confirms the strong connection of IBD and gastrointestinal microbiome. Among most important features in three-class classification are species Staphylococcus hominis, Porphyromonas endodontalis, Slackia piriformis and genus Bacteroidetes.


Assuntos
Colite Ulcerativa , Doença de Crohn , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Actinobacteria , Bacteroidetes , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/microbiologia , Doença de Crohn/diagnóstico , Doença de Crohn/microbiologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/microbiologia , Aprendizado de Máquina , Porphyromonas endodontalis , Staphylococcus hominis
2.
Int J Oral Sci ; 13(1): 31, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593756

RESUMO

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.


Assuntos
Colite Ulcerativa , Porphyromonas gingivalis , Desiminases de Arginina em Proteínas , Animais , Colite Ulcerativa/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/patogenicidade , Fatores de Virulência
3.
Medicine (Baltimore) ; 100(32): e26932, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397940

RESUMO

ABSTRACT: To determine the differences in intestinal flora between Uygur and Han patients with ulcerative colitis (UC).Microbial diversity and structural composition of fecal bacteria from patients with UC and their matched healthy spouses or first-degree relatives were analyzed using high-throughput sequencing technology.The fecal microbial diversity and abundance index of Uygur patients with UC (UUC) were significantly lower compared with the Uygur normal control group, while there was no significant difference between the Han UC patients (HUC) and the Han normal control group (HN). Compared with their respective control groups, Uygur UC patients and Han UC patients had a different main composition of human intestinal flora (P < .05). The abundance of Burkholderia, Caballeronia, Paraburkholderia in the UUC group were higher compared with the HUC group, while Faecalibacterium, Bifidobacterium, and Blautia in the HUC group were higher than those in the UUC group (P < .05). Veillonella in the UUC group was higher than that in the Uygur normal control group group, while Subdoligranulum and Ruminococcaceae_UCG-002 were significantly lower (P < .05). Prevotella_9 in the HUC group was significantly higher than that in HN group, while Blautia, Anaerostipes, and [Eubacterium]_hallii_group were significantly lower. Moreover, the top 6 species in order of importance were Christensenellaceae_R_7_group, Ruminococcae_ucg_005, Ruminococcae_ucg_010, Ruminococcae_ucg_013, Haemophilus, and Ezakiella.The difference in intestinal microflora structure may be one of the reasons for the clinical heterogeneity between Uygur and Han patients with UC. Christensenellaceae_R_7_group, Ruminococcae_ucg_005, Ruminococcae_ucg_010, Ruminococcae_ucg_013, Haemophilus, and Ezakiella could be used as potential biomarkers for predicting UC.


Assuntos
Bactérias/isolamento & purificação , Colite Ulcerativa/microbiologia , Grupos Étnicos , Microbioma Gastrointestinal , Adulto , Bactérias/genética , China/epidemiologia , Colite Ulcerativa/etnologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Estudos Retrospectivos , Adulto Jovem
4.
Sci Rep ; 11(1): 13743, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215773

RESUMO

This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.


Assuntos
Colite Ulcerativa/microbiologia , Colo/microbiologia , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Adulto , Bacteroides/genética , Bacteroides/isolamento & purificação , Clostridiales/genética , Clostridiales/isolamento & purificação , Colite Ulcerativa/patologia , Colite Ulcerativa/terapia , Fezes/microbiologia , Feminino , Humanos , Mucosa Intestinal/microbiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevotella/genética , Prevotella/isolamento & purificação , Recidiva
5.
Nutrients ; 13(6)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071065

RESUMO

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.


Assuntos
Colite Ulcerativa/terapia , Microbioma Gastrointestinal , Pouchite/terapia , Colite Ulcerativa/microbiologia , Dieta Mediterrânea , Ácidos Graxos Ômega-3/uso terapêutico , Transplante de Microbiota Fecal/métodos , Humanos , Doenças Inflamatórias Intestinais/terapia , Microbiota , Pouchite/microbiologia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico
6.
Microbiologyopen ; 10(2): e1181, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33970546

RESUMO

Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.


Assuntos
Bactérias/classificação , Colite Ulcerativa/microbiologia , Colite/microbiologia , Disbiose/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal , Adulto , Bactérias/genética , Biodiversidade , DNA Bacteriano , Feminino , Voluntários Saudáveis , Humanos , Complexo Antígeno L1 Leucocitário/análise , Masculino , RNA Ribossômico 16S , Índice de Gravidade de Doença
7.
BMC Microbiol ; 21(1): 138, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947329

RESUMO

BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.


Assuntos
Bactérias/isolamento & purificação , Biodiversidade , Colite Ulcerativa/microbiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/microbiologia , Bactérias/classificação , Bactérias/genética , China , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , DNA Bacteriano/genética , Disbiose/complicações , Humanos
8.
J Immunol Res ; 2021: 6679316, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007853

RESUMO

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disorder in the colon and rectum leading to low life-quality and high societal costs. Ursolic acid (UA) is a natural product with pharmacological and biological activities. The studies are aimed at investigating the protective and treatment effects of UA against the dextran sulfate sodium- (DSS-) induced UC mouse model and its underlying mechanism. UA was orally administered at different time points before and after the DSS-induced model. Mice body weight, colon length, and histological analysis were used to evaluate colon tissue damage and therapeutic evaluation. Intestinal transcriptome and microbe 16 s sequencing was used to analyze the mechanisms of UA in the prevention and treatment of UC. The early prevention effect of UA could effectively delay mouse weight loss and colon length shorten. UA alleviated UC inflammation and lowered serum and colon IL-6 levels. Three classical inflammatory pathways: MAPKs, IL-6/STAT3, and PI3K were downregulated by UA treatment. The proportion of macrophages and neutrophils in inflammatory cell infiltration was reduced in UA treatment groups. UA could significantly reduce the richness of intestinal flora to avoid the inflammatory response due to the destruction of the intestinal epithelial barrier. The function of UA against UC was through reducing intestinal flora abundance and regulating inflammatory and fatty acid metabolism signaling pathways to affect immune cell infiltration and cytokine expression.


Assuntos
Colite Ulcerativa/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Triterpenos/administração & dosagem , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/microbiologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/imunologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
9.
Biomed Pharmacother ; 139: 111127, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33819810

RESUMO

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is rising constantly all over the world. However, current medical treatments are not universally practical. Microcin J25 (MccJ25), a member of the lasso peptides class, has excellent antimicrobial activity both in vitro and in vivo. Here, we assessed the anti-inflammatory effects of MccJ25 through DSS-induced UC mouse model. MccJ25 significantly ameliorated the UC-associated parameters such as decreased body weight, increased disease activity index (DAI) and shortened colon length. MccJ25 also provides barrier protection by preserving structural integrity and reducing inflammatory infiltrates of colon epithelium. The underlying mechanism may be associated with gut microbiota. To test this uncertainty, co-housing experiment was performed, and results indicate homogenized microbiota could relief the inflammatory. Meanwhile, we also proved the prominent role of the possible targets of MccJ25, namely genus Lactobacillus, Bacteroides and Akkermansia (as well as the possible strains related to the important OTUs) in inflammation status through comprehensive analysis. In conclusion, MccJ25 effectively attenuates inflammation and improves disrupted barrier function, and the MccJ25-modified gut microbiota plays a central role in this process.


Assuntos
Anti-Inflamatórios/uso terapêutico , Bacteriocinas/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Proteínas Recombinantes/uso terapêutico , Animais , Colite Ulcerativa/induzido quimicamente , Colo/enzimologia , Colo/patologia , Sulfato de Dextrana , Feminino , Mucosa Intestinal/enzimologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Citotóxicas Formadoras de Poros
10.
Sci Rep ; 11(1): 7262, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790336

RESUMO

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ - 0.460, p < 0.005) and B. wadsworthia (ρ - 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.


Assuntos
Bilophila/metabolismo , Clostridiales/metabolismo , Colite Ulcerativa/microbiologia , Colo/microbiologia , Mucosa Intestinal/microbiologia , Adulto , Idoso , Butiratos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Sci Rep ; 11(1): 7286, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790314

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) induced by dysregulation of the immune response in the intestinal mucosa. Although the underlying mechanisms of UC development are not fully understood, disruption of gut microbiota, "dysbiosis", is thought to lead to the development of IBD. Persimmon (Ebenaceae Diospyros kaki Thunb.)-derived tannin, which is a condensed polymeric tannin consisting of catechin groups, has antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we assessed the effect of persimmon-derived tannin on a murine model of UC established by dextran sulfate sodium-induced colitis in female mice. Dietary supplementation of tannin significantly decreased disease activity and colon inflammation. A hydrolysate of tannin directly suppressed expression of inflammatory genes in macrophages in vitro. In faecal microbiota, the relative abundance of Bacteroides was increased significantly by tannin supplementation. Alpha-diversity indices in colitis-induced mice were significantly higher in the tannin diet group compared with the control diet group. Additionally, expansion of Enterobacteriaceae and Enterococcus, which is associated with disease progression of IBD, was remarkably suppressed in the tannin diet group. These results suggest that persimmon-derived tannin ameliorates colon inflammation in UC through alteration of the microbiota composition and immune response, which may be a promising candidate for IBD therapy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Taninos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Células Cultivadas , Colite Ulcerativa/microbiologia , Suplementos Nutricionais , Diospyros/química , Feminino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Taninos/administração & dosagem , Taninos/farmacologia
12.
Sci Rep ; 11(1): 8641, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883600

RESUMO

Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2-6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3-10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.


Assuntos
Colite Ulcerativa/microbiologia , Fezes/microbiologia , Adulto , Progressão da Doença , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , Recidiva , Indução de Remissão/métodos , Adulto Jovem
13.
J Food Sci ; 86(5): 2118-2130, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33884622

RESUMO

ß-Carotene displays antioxidant and anti-inflammatory activities and prevents the development of cancer. Ulcerative colitis (UC) is a kind of inflammatory bowel disease that is accompanied by a certain risk of colon cancer. However, the role of ß-carotene in the modulation of gut microbiota and UC improvement is unclear. In this research, the properties of ß-carotene on anti-inflammatory and the composition of gut microbiota were evaluated in a rat model of UC induced by dextran sulfate sodium (DSS). The results revealed that ß-carotene significantly (p < 0.05) decreased the severity of colitis in rats, as assessed using body weight (6.00 ± 1.73%), colon length (22.23 ± 0.53%), and disease activity index, and improved the structure of the colon damaged. Moreover, colonic levels of proinflammatory cytokines were significantly lower following ß-carotene supplementation. ß-Carotene intervention also lowered the expression levels of phosphorylated p65 (0.60 ± 0.02), p38 (0.57 ± 0.00), Erk (0.63 ± 0.04), and JNK (0.70 ± 0.00). The result of the relative abundance of gut microbiota showed that DSS administration significantly changed the microbial structure at the phylum and genus levels of rats. Furthermore, ß-carotene treatment significantly increased the abundance of Faecalibacterium, the levels of which negatively correlated with the levels of inflammatory cytokines. Faecalibacterium may be a potential target in the alleviation of DSS-induced UC. ß-Carotene can alleviate DSS-induced UC through the regulation of gut microbiota. This study provides a reference for the rational use of ß-carotene in the treatment of UC. PRACTICAL APPLICATION: ß-Carotene can relieve ulcerative colitis and regulate the gut microbiota; the nutritional intervention of ß-carotene enhancing animal health.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , beta Caroteno/farmacologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/microbiologia , Citocinas/metabolismo , Masculino , Provitaminas/farmacologia , Ratos , Ratos Sprague-Dawley
14.
Exp Biol Med (Maywood) ; 246(13): 1563-1575, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33926254

RESUMO

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.


Assuntos
Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Akkermansia/isolamento & purificação , Akkermansia/patogenicidade , Animais , Colite Ulcerativa/etiologia , Colite Ulcerativa/microbiologia , Colo/metabolismo , Colo/microbiologia , Sulfato de Dextrana/toxicidade , Helicobacter/isolamento & purificação , Helicobacter/patogenicidade , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/metabolismo , Fator de Crescimento Transformador beta/metabolismo
15.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33834198

RESUMO

How best to utilize the microbial taxonomic abundances in regard to the prediction and explanation of human diseases remains appealing and challenging, and the relative nature of microbiome data necessitates a proper feature selection method to resolve the compositional problem. In this study, we developed an all-in-one platform to address a series of issues in microbiome-based human disease prediction and taxonomic biomarkers discovery. We prioritize the interpretation, runtime and classification accuracy of the distal discriminative balances analysis (DBA-distal) method in selecting a set of distal discriminative balances, and develop DisBalance, a comprehensive platform, to integrate and streamline the workflows of disease model building, disease risk prediction and disease-related biomarker discovery for microbiome-based binary classifications. DisBalance allows the de novo model-building and disease risk prediction in a very fast and convenient way. To facilitate the model-driven and knowledge-driven discoveries, DisBalance dedicates multiple strategies for the mining of microbial biomarkers. The independent validation of the models constructed by the DisBalance pipeline is performed on seven microbiome datasets from the original article of DBA-distal. The implementation of the DisBalance platform is demonstrated by a complete analysis of a shotgun metagenomic dataset of Ulcerative Colitis (UC). As a free and open-source, DisBlance can be accessed at http://lab.malab.cn/soft/DisBalance. The source code and demo data for Disbalance are available at https://github.com/yangfenglong/DisBalance.


Assuntos
Biologia Computacional/métodos , Internet , Metagenoma/genética , Metagenômica/métodos , Microbiota/genética , Biomarcadores/análise , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Colite Ulcerativa/microbiologia , Doença/classificação , Doença/genética , Humanos , Modelos Logísticos , Reprodutibilidade dos Testes
16.
PLoS One ; 16(3): e0246393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33690604

RESUMO

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn's colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000-2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4-14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation 'the colonic ectopy ileal metaplasia formation' conspicuously of pathogenic importance in CC.


Assuntos
Colite Ulcerativa/metabolismo , Colo/citologia , Doença de Crohn/metabolismo , Enterotoxinas/farmacologia , Organoides/citologia , alfa-Defensinas/metabolismo , Idoso , Linhagem da Célula , Células Cultivadas , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Humanos , Modelos Logísticos , Masculino , Mucina-6/metabolismo , Técnicas de Cultura de Órgãos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Proteômica , Estudos Retrospectivos
17.
Biomed Pharmacother ; 137: 111420, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761623

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), which is a common idiopathic digestive disease without a specific cure or treatment for improvement. Because Polygoni multiflori Radix has a traditional medicinal use to treat intestinal diseases, and the water extract of this herbal medicine had a positive influence on dextran sulfate sodium (DSS) induced UC model in our study. Meanwhile 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as the major component of the water extract of Polygoni multiflori Radix with yield of more than 10% exhibited the remarkable anti-inflammatory activity in vivo and in vitro, we predicted that TSG may contribute to benefit intestinal tract presented by the water extract of Polygoni multiflori Radix. Therefore, the present study aims to explore the pharmacological effect of this compound on UC model and its possible mechanism to regulate intestinal function through gut microbiota. METHODS: Ulcerative colitis model was established in BALb/c mice by continuously administrating 3% (w/v) DSS aqueous solution for one week. The disease activity index (DAI), colon length, histopathological examination by H&E and the levels of tight junction proteins (TJP) by immunofluorescence staining were performed in ulcerative colitis model following the protocol. Furthermore, the levels of main inflammatory factors like TNF-α, IL-ß, IL-6, and IL-10 were analyzed by the ELIZA kits for the further confirmation of anti-inflammatory activity of TSG on ulcerative colitis model. Finally, 16S rDNA sequencing technology was conducted to explore the composition and relative abundance of gut microbiota of different treatment groups. RESULTS: TSG treatments effectively increased body weight about 5% of those in DSS group (p < 0.001) as well remarkably reduced the DAI scores to the 50% of those in DSS group (p < 0.001) in the UC model. TSG treatments of either 25 mg/kg (TSG-25) or 100 mg/kg (TSG-100) dosage restored epithelial barrier structure and exhibited obviously intact colon histology with reduced signs of inflammatory cells infiltration, preserved epithelia barrier, restored crypt structure, and increased numbers of goblet cells. TSG treatments could markedly lessen the histopathologic score two or three times than those in DSS group (p < 0.001). Especially for TSG-100 treatment, the fluorescence intensity of ZO-1 and Occludin were nearly back to 80% of those in normal group, and were 1.5 times more than those in the DSS group (p < 0.001). Additionally, direct evidence pointed to TSG as a therapeutically active molecule in the prevention and treatment of UC by significantly reducing the production of these pro-inflammatory cytokines like TNF-α, IL-1ß, and IL-6 (p < 0.05-0.001) and increasing the levels of anti-inflammatory cytokine IL-10 (p < 0.05-0.001). Finally, it was found TSG treatments significantly raised the relative abundances of Firmicutes and Bacteroidetes with a dose-dependently and improved the homeostasis of the gut microbiota composition which disrupted by DSS through increasing genus level Lachnospiraceae_NK4A136 and decreasing genus level of Helicobacter, Bacteroides, Parabacteroides. CONCLUSION: The present results suggested that TSG treatments had a desirable pharmacological effect on acute colitis induced by DSS in the mice as well showed the possible mechanism relate to improve the intestinal function through balancing the gut microbiota of intestinal flora.


Assuntos
Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/prevenção & controle , Sulfato de Dextrana , Microbioma Gastrointestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/microbiologia , Colo/patologia , Citocinas/metabolismo , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Glucosídeos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais , Plantas Medicinais/química , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Estilbenos/química , Proteínas de Junções Íntimas/metabolismo
18.
PLoS One ; 16(3): e0248427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711050

RESUMO

BACKGROUND & AIMS: Helicobacter pylori (H. pylori) infection remains high in China though the incidence of inflammatory bowel disease (IBD) has increased. Our aim was to investigate the relationship between the prevalence of H. pylori and inflammatory bowel disease. METHODS: Hospitalized IBD patients including Crohn's disease (CD) and ulcerative colitis (UC) who had tested H. pylori antibody were enrolled. Controls were chose from age- and sex- matched healthy physical examination people who had H. pylori antibody test in a 1:2 fashion (IBD patients:controls). IBD medical history was recorded. All patients were typed by the Montreal classification. Mayo Clinic score and the Harvey-Bradshaw Severity Index were used to evaluate their disease activity. Patients and controls that had H. pylori eradication therapy before were excluded. RESULTS: Two hundred and sixty IBD patients including 213 CD patients and 47 UC patients, and 520 controls were involved in this study. The prevalence of H. pylori infection in IBD patients (9.6%, 25/260) and IBD newly diagnosed patients (12.1%, 8/66), as well as CD patients (8.9%, 19/213) including CD newly diagnosed patients (10.6%, 5/47) and UC patients (12.8%, 6/47) was significantly lower than controls (29.8%, 155/520) (p = 2.796*10-10, 0.007, 5.723*10-9, 0.016, 0.014), while there was no statistically difference between UC newly diagnosed patients and the controls, and IBD patients with different disease type, disease activity and treatment history. CONCLUSIONS: H. pylori infection had a negative association with IBD, especially CD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Adulto , China/epidemiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/microbiologia , Doença de Crohn/epidemiologia , Doença de Crohn/microbiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
19.
Ann Agric Environ Med ; 28(1): 56-60, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33775068

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is reactivated by the use of immunosuppressive drugs. CMV infection may produce IBD flares refractory to standard therapy. OBJECTIVE: The aim of our study was to assess the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of CMV colitis in patients with ulcerative colitis (UC) flare. MATERIAL AND METHODS: A total of 8 children, with mild to severe UC, positive for CMV PCR in colonic biopsies, received 50-100 ml FMT by nasogastric tube on 5 consecutive days in each of 2 weeks. During the study, the subjects were treated with 5ASA and FMT. Immunosuppressant therapy was withdrawn, when CMV colitis was diagnosed by positive DNA PCR in colonic tissues. The clinical response was defined as a decrease of Paediatric UC Activity Index by ≥20 points. RESULTS: At the 6th week of the study, negative colonic CMV DNA PCR was measured after 10 infusions in 7/8 patients. For one boy, 20 infusions were administered to assess CMV elimination from colonic biopsies. A clinical response was observed in 3/8 patients, with clinical remission in 3/8 patients. Faecal calprotectin decreased significantly in 3 patients. CRP normalized in 2 patients after 6 weeks. No serious adverse effects were observed during and after infusions. CONCLUSIONS: FMT seems to be an effective and safe treatment option for CMV colitis in children with UC. This is the first study to demonstrate the application of FMT as a new therapeutic option for CMV colitis.


Assuntos
Colite Ulcerativa/terapia , Infecções por Citomegalovirus/terapia , Citomegalovirus/fisiologia , Transplante de Microbiota Fecal , Adolescente , Criança , Pré-Escolar , Colite Ulcerativa/microbiologia , Colite Ulcerativa/virologia , Colo/microbiologia , Colo/virologia , Infecções por Citomegalovirus/microbiologia , Infecções por Citomegalovirus/virologia , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos
20.
Medicine (Baltimore) ; 100(7): e24845, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607855

RESUMO

ABSTRACT: Despite the establishment of the links between ulcerative colitis (UC) and depression, between UC and gut microbiota, few correlations between depression and gut microbiota have yet been demonstrated especially in ulcerative colitis patients. The objective of our study was therefore to determine whether the comorbidity of depressive disorder in ulcerative colitis patients correlate with alterations in the gut microbiota and to identify the specific microbiota signatures associated with depression.Between March 2017 and February 2018, 31 healthy volunteers, 31 UC patients without depression, and 31 UC patients with depression from Longhua Hospital were enrolled. Clinical data and fecal samples were collected for each patient. Fecal bacteria were identified using 16 s rRNA sequencing. We compared microbial composition among the 3 groups using bioinformatic analysis.Patients with UC with depression had higher disease severity (P < .05). The UC without depression group had moderate reduction of microbial abundance and uniformity compared to the control group. The UC with depression group had the lowest microbial abundance. With regard to the vital bacteria in the microbiota-gut-brain axis, patients with UC and depression had the lowest abundance of Firmicutes, Clostridia, and Clostridiales but the highest abundance of Proteobacteria, Gammaproteobacteria, and Bacilli.The presence of depression in UC patients presented significant differences in the composition of gut microbiota compared with UC patients without depression, with increased abundance of Firmicutes and reduced abundance of Proteobacteria.


Assuntos
Colite Ulcerativa/microbiologia , Depressão/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Estudos de Casos e Controles , Clostridiales/crescimento & desenvolvimento , Colite Ulcerativa/psicologia , Comorbidade , Biologia Computacional/métodos , Depressão/complicações , Feminino , Firmicutes/crescimento & desenvolvimento , Gammaproteobacteria/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteobactérias/crescimento & desenvolvimento , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença
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