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1.
Int J Nanomedicine ; 14: 8361-8378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749615

RESUMO

Purpose: This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). Materials and methods: 5-, 30- and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment. Results: According to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. Conclusion: PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.


Assuntos
Colite/induzido quimicamente , Colite/terapia , Nanopartículas Metálicas/uso terapêutico , Platina/uso terapêutico , Doença Aguda , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Colite/microbiologia , Colo/microbiologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/patologia , Lipopolissacarídeos , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
2.
J Agric Food Chem ; 67(48): 13299-13306, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31674784

RESUMO

l-Arabinose is a monosaccharide extracted from plants or fibers, which is known to have a variety of functional properties. In this study, we aim to investigate whether l-arabinose could inhibit colitis by modulating gut microbiota. l-Arabinose was administered in mice daily in a dextran sodium sulfate (DSS)-induced colitis model. The histological analysis, disease index, and the expression of inflammatory genes were measured. 16S-rRNA sequence analysis was performed to investigate gut microbiota. Intriguingly, we found that l-arabinose could repress DSS-induced colitis and inhibit p38-/p65-dependent inflammation activation. Besides that, our data revealed that l-arabinose-modulated DSS-induced gut microbiota were disturbed. Additionally, the perturbed gut microbiota was responsible for the suppressive effects of l-arabinose on DSS-induced colitis treated with antibiotics. Lastly, Caco-2 cells were used to confirm the protective effects of l-arabinose in colitis or inflammatory bowel disease. As expected, the protein expression levels in Caco-2 cells of pro-inflammatory genes, which were treated with l-arabinose and incubated with or without tumor necrosis factor alpha. Our work suggested that l-arabinose exerts anti-inflammation effects in DSS-induced colitis. These beneficial effects have correlations with the composition, diversity, and abundance of the gut microbiota regulated by l-arabinose. l-Arabinose could be a remarkable candidate as a functional food or novel therapeutic strategy for intestinal health.


Assuntos
Arabinose/administração & dosagem , Colite/tratamento farmacológico , Colite/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Colite/induzido quimicamente , Colite/imunologia , Citocinas/genética , Citocinas/imunologia , Sulfato de Dextrana/efeitos adversos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
3.
J Agric Food Chem ; 67(48): 13282-13298, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690068

RESUMO

Dietary supplementation with conjugated linoleic acid (CLA) has been reported to alleviate the effect of colitis in mice, but the mechanisms involved need further exploration. The study aimed to investigate how orally administered CLA alleviates dextran sulfate sodium (DSS)-induced colitis in mice. CLA was administered in five different doses: 40, 20, 10, 5, and 2.5 mg/day. Doses of CLA at 10 mg/day and higher alleviated colitis symptoms and reduced inflammation induced by DSS, in which 40, 20, and 10 mg/day CLA significantly increased the concentration of mucin2 and goblet cells, but neither 5 mg/day CLA nor 2.5 mg/day CLA had any effects. Meanwhile, 40 and 20 mg/day CLA treatments significantly upregulated the concentration of tight junction proteins (ZO-1, occludin, and claudin-3) and ameliorated epithelial apoptosis caused by DSS. Moreover, oxidative-stress-related enzymes (superoxide dismutase, glutathione peroxidase, and catalase) and inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-10, and IL-6] were modulated by 40 and 20 mg/day CLA. Furthermore, 40 mg/day CLA rebalanced the gut microbiota damaged by DSS, including reducing Bacteroides and increasing Bifidobacterium and Odoribacter. In conclusion, CLA supplementation alleviated DSS-induced colitis in a dose-dependent manner by modulating inflammatory cytokines and oxidation stress, maintaining the mucosal barrier, and reverting microbiota changes.


Assuntos
Colite/tratamento farmacológico , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Ácidos Linoleicos Conjugados/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Citocinas/genética , Sulfato de Dextrana/efeitos adversos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Adv Exp Med Biol ; 1197: 97-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732937

RESUMO

The colonization of body surfaces, notably of the intestine, by a complex microbiota is generally highly mutualistic, where vital functions are provided by the commensal microbiota to the host, including the synthesis of vitamins, the degradation of complex polysaccharides into small chain fatty acids (which are essential for the maintenance of the intestinal epithelial barrier), and, finally, the outcompetition of pathogens that accidentally gain access to the body ("colonization resistance") (Chow et al. 2011; Backhed 2005). However, under certain conditions, such as changes of environmental factors in a genetically predisposed host, some of these normally symbiotic bacteria may act as pathogens and induce pathologies. Hence, the term "pathobionts" was coined for these bacterial species with ambiguous biological properties (Round et al. 2009).


Assuntos
Colite , Helicobacter , Animais , Colite/microbiologia , Modelos Animais de Doenças , Helicobacter/fisiologia , Humanos , Intestinos/microbiologia
5.
Cell Physiol Biochem ; 53(5): 774-793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647207

RESUMO

BACKGROUND/AIMS: Deregulation of the complex interaction among host genetics, gut microbiota and environmental factors on one hand and aberrant immune responses on the other hand, are known to be associated with the development of inflammatory bowel disease. Recent studies provided strong evidence that autophagy plays a key role in the etiology of Crohn's disease (CD). Probiotics may exhibit many therapeutic properties, including anti-inflammatory abilities. While successful results have been obtained in ulcerative colitis patients, probiotics remain inefficient in CD for unknown reason. It remains therefore important to better understand their molecular mechanisms of action. METHODS: The activation of autophagy was examined by stimulating bone marrow-derived dendritic cells by the bacteria, followed by confocal microscopy and western blot analysis. The impact of blocking in vitro autophagy was performed in peripheral blood mononuclear cells using 3-methyl adenine or bafilomycin followed by cytokine secretion measurement by ELISA. The role of autophagy in the anti-inflammatory capacities of the bacterial strains was evaluated in vivo using an acute trinitrobenzene sulfonic acid-induced murine model of colitis. The impact of BMDC was evaluated by adoptive transfer, notably using bone marrow cells derived from autophagy-related 16-like 1-deficient mice. RESULTS: We showed that selected lactobacilli and bifidobacteria are able to induce autophagy activation in BMDCs. Blocking in vitro autophagy abolished the capacity of the strains to induce the release of the anti-inflammatory cytokine interleukin-10, while it exacerbated the secretion of the pro-inflammatory cytokine interleukin-1ß. We confirmed in the TNBS-induced mouse model of colitis that autophagy is involved in the protective capacity of these selected strains, and showed that dendritic cells are involved in this process. CONCLUSION: We propose autophagy as a novel mechanism involved in the regulatory capacities of probiotics.


Assuntos
Autofagia , Bifidobacterium/fisiologia , Lactobacillus/fisiologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteínas Relacionadas à Autofagia , Células da Medula Óssea/citologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Feminino , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Macrolídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout
6.
J Agric Food Chem ; 67(41): 11408-11419, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31556290

RESUMO

In this study, the effects of 2-O-ß-d-glucopyranosyl-l-ascorbic acid (AA-2ßG), a natural ascorbic acid derivative from the fruits of Lycium barbarum, on treating the dextran sulfate sodium (DSS)-induced colitis in mice were investigated. The results revealed that AA-2ßG had palliating effects on DSS-induced inflammatory bowel disease (IBD) in terms of slowing down the trends of body weight and solid fecal mass loss, reducing colitis disease activity index, improving serum physiological and biochemical indicators, increasing colon length, blocking proinflammatory cytokines, and increasing tight junction proteins. Additionally, AA-2ßG treatment could promote the production of short-chain fatty acids and modulate the composition of the gut microbiota. The key bacteria related to IBD were found to be Porphyromonadaceae, Prevotellaceae, Rikenellaceae, Parasutterella, Parabacteroides, and Clostridium. The results indicated that AA-2ßG might treat IBD through the regulation of gut microbiota, suggesting that AA-2ßG has the potential to be used as a dietary supplement in the treatment of IBD.


Assuntos
Ácido Ascórbico/administração & dosagem , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lycium/química , Extratos Vegetais/administração & dosagem , Animais , Ácido Ascórbico/química , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colite/genética , Colite/imunologia , Colite/microbiologia , Citocinas/genética , Citocinas/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Frutas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
7.
J Microbiol Biotechnol ; 29(9): 1369-1374, 2019 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564078

RESUMO

We isolated Lactobacillus mucosae NK41 and Bifidobacterium longum NK46 from human feces, which induced BDNF expression in corticosterone-stimulated SH-SY5Y cells, and examined their anti-depressive effects in mice. NK41, NK46, and their (1:1) mixture significantly mitigated immobilization stress (IS)-induced anxiety-like/depressive behaviors, hippocampal NF-κB activation, BDNF expression, Iba1+ cell population, and blood corticosterone, TNF-α, IL- 6, and lipopolysaccharide levels. Furthermore, they inhibited colitis marker NF-κB activation, and TNF-α expression in mice with IS-induced anxiety/depression. They additionally suppressed gut Proteobacteria and Bacteroidetes populations and bacterial lipopolysaccharide production. These findings suggest that NK41 and NK46 may alleviate anxiety/depression and colitis by suppressing gut dysbiosis.


Assuntos
Ansiedade/dietoterapia , Bifidobacterium longum , Depressão/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus , Probióticos/farmacologia , Probióticos/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ansiedade/sangue , Ansiedade/microbiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Colite/microbiologia , Colite/patologia , Corticosterona/sangue , Depressão/sangue , Depressão/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/patologia , Fezes/microbiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Interleucina-6/sangue , Lipopolissacarídeos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , NF-kappa B/metabolismo , Probióticos/administração & dosagem , Estresse Psicológico/sangue , Estresse Psicológico/microbiologia , Estresse Psicológico/psicologia , Fator de Necrose Tumoral alfa/sangue
8.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31481410

RESUMO

Fibrosis is a significant complication of intestinal disorders associated with microbial dysbiosis and pathobiont expansion, notably Crohn's disease (CD). Mechanisms that favor fibrosis are not well understood, and therapeutic strategies are limited. Here we demonstrate that colitis-susceptible Il10-deficient mice develop inflammation-associated fibrosis when monoassociated with adherent/invasive Escherichia coli (AIEC) that harbors the yersiniabactin (Ybt) pathogenicity island. Inactivation of Ybt siderophore production in AIEC nearly abrogated fibrosis development in inflamed mice. In contrast, inactivation of Ybt import through its cognate receptor FyuA enhanced fibrosis severity. This corresponded with increased colonic expression of profibrogenic genes prior to the development of histological disease, therefore suggesting causality. fyuA-deficient AIEC also exhibited greater localization within subepithelial tissues and fibrotic lesions that was dependent on Ybt biosynthesis and corresponded with increased fibroblast activation in vitro Together, these findings suggest that Ybt establishes a profibrotic environment in the host in the absence of binding to its cognate receptor and indicate a direct link between intestinal AIEC and the induction of inflammation-associated fibrosis.


Assuntos
Colite/microbiologia , Escherichia coli/metabolismo , Fibrose/etiologia , Inflamação/microbiologia , Interleucina-10/metabolismo , Fenóis/metabolismo , Tiazóis/metabolismo , Animais , Aderência Bacteriana , Colite/complicações , Colite/patologia , Regulação Bacteriana da Expressão Gênica , Vida Livre de Germes , Humanos , Inflamação/patologia , Interleucina-10/genética , Camundongos , Camundongos Knockout , Mutação
10.
Chin Med J (Engl) ; 132(16): 1951-1958, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31335471

RESUMO

BACKGROUND: The effect and mechanism of Saccharomyces boulardii (Sb) in inflammatory bowel disease are unclear. The objective of the study was to evaluate the impact of Sb on intestinal mucosal barrier and intestinal flora in a colitis mouse model. METHODS: Forty C57BL/6J male mice were randomly assigned to five groups: normal control group (A), pathologic control group (B), Sb treatment group (C), mesalazine treatment group (D), and Sb combined with mesalazine treatment group (E). Colitis was induced by the addition of 2.5% (wt/vol) dextran sodium sulfate (DSS) in the drinking water ad libitum for 7 days. The general condition, weight change, stool property, and bloody stool level of mice were observed to evaluate the disease activity index. The expression of zona occludens-1 (ZO-1) and occludin in intestinal tissue were measured by immunohistochemistry. The level of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 in plasma was measured by enzyme linked immunosorbent assay. Inter-cellular tight junctions were observed by transmission electron microscopy. The feces and intestinal contents were collected sterilely, and intestinal flora was analyzed by 16S rRNA sequencing. RESULTS: Compared with group B, Sb reduced the disease activity index and histological score of group C (disease activity index: group B 2.708 ±â€Š0.628, group C 1.542 ±â€Š0.616, PBC = 0.005; histological score: group B 9.875 ±â€Š3.271, group C 4.750 ±â€Š1.832, PBC = 0.005) in DSS-induced colitis in mice. Sb exerted a protect effect on the expression of ZO-1 (group B 2.075 ±â€Š1.176, group C 4.225 ±â€Š1.316, PBC = 0.019) and occludin (group B 2.200 ±â€Š0.968, group C 3.525 ±â€Š1.047, PBC = 0.023). Compared with group B, Sb decreased the level of TNF-α and IL-8 of group C (TNF-α: group B 716.323 ±â€Š44.691 ng/L, group C 521.740 ±â€Š90.121 ng/L, PBC = 0.001; IL-8: group B 128.992 ±â€Š11.475 pg/mL, group C 106.283 ±â€Š15.906 pg/mL, PBC = 0.012). Treatment with Sb preserved the tight junctions and ameliorated microvilli and inter-cellular space. Treatment with Sb also showed its own characteristics: a higher percentage of Bacteroidetes and a lower percentage of Firmicutes, with significant differences or a significant trend. The proportion of the S24-7 family was increased significantly in the Sb treatment group. CONCLUSIONS: Sb shows an anti-inflammatory effect and has a protective effect on the intestinal mucosal mechanical barrier. Sb may up-regulate the abundance of family S24-7 specifically, and maybe a mechanism underlying its function.


Assuntos
Colite/induzido quimicamente , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Mucosa Intestinal/microbiologia , Saccharomyces boulardii/fisiologia , Animais , Colite/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Distribuição Aleatória , Proteína da Zônula de Oclusão-1/metabolismo
11.
PLoS Pathog ; 15(7): e1007915, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329635

RESUMO

Expression of ABO and Lewis histo-blood group antigens by the gastrointestinal epithelium is governed by an α-1,2-fucosyltransferase enzyme encoded by the Fut2 gene. Alterations in mucin glycosylation have been associated with susceptibility to various bacterial and viral infections. Salmonella enterica serovar Typhimurium is a food-borne pathogen and a major cause of gastroenteritis. In order to determine the role of Fut2-dependent glycans in Salmonella-triggered intestinal inflammation, Fut2+/+ and Fut2-/- mice were orally infected with S. Typhimurium and bacterial colonization and intestinal inflammation were analyzed. Bacterial load in the intestine of Fut2-/- mice was significantly lower compared to Fut2+/+ mice. Analysis of histopathological changes revealed significantly lower levels of intestinal inflammation in Fut2-/- mice compared to Fut2+/+ mice and measurement of lipocalin-2 level in feces corroborated histopathological findings. Salmonella express fimbriae that assist in adherence of bacteria to host cells thereby facilitating their invasion. The std fimbrial operon of S. Typhimurium encodes the π-class Std fimbriae which bind terminal α(1,2)-fucose residues. An isogenic mutant of S. Typhimurium lacking Std fimbriae colonized Fut2+/+ and Fut2-/- mice to similar levels and resulted in similar intestinal inflammation. In vitro adhesion assays revealed that bacteria possessing Std fimbriae adhered significantly more to fucosylated cell lines or primary epithelial cells in comparison to cells lacking α(1,2)-fucose. Overall, these results indicate that Salmonella-triggered intestinal inflammation and colonization are dependent on Std-fucose interaction.


Assuntos
Fímbrias Bacterianas/metabolismo , Fucose/metabolismo , Salmonella typhimurium/patogenicidade , Animais , Aderência Bacteriana , Colite/etiologia , Colite/metabolismo , Colite/microbiologia , Feminino , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/genética , Fucosiltransferases/deficiência , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Camundongos Knockout , Óperon , Salmonelose Animal/etiologia , Salmonelose Animal/metabolismo , Salmonelose Animal/microbiologia , Salmonella typhimurium/genética , Salmonella typhimurium/fisiologia
12.
Chin Med J (Engl) ; 132(15): 1833-1842, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31268903

RESUMO

BACKGROUND: Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. METHODS: C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. RESULTS: After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315). CONCLUSIONS: Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.


Assuntos
Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos , Probióticos/farmacologia , Probióticos/uso terapêutico , Análise de Variância , Animais , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Microbioma Gastrointestinal/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Distribuição Aleatória , Álcoois Açúcares/farmacologia , Álcoois Açúcares/uso terapêutico
13.
Infect Immun ; 87(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235639

RESUMO

Salmonella enterica serovar Typhimurium (S. Typhimurium) induces inflammatory changes in the ceca of streptomycin-pretreated mice. In this mouse model of colitis, the type III secretion system 1 (T3SS-1) has been shown to induce rapid inflammatory change in the cecum at early points, 10 to 24 h after infection. Five proteins, SipA, SopA, SopB, SopD, and SopE2, have been identified as effectors involved in eliciting intestinal inflammation within this time range. In contrast, a T3SS-1-deficient strain was shown to exhibit inflammatory changes in the cecum at 72 to 120 h postinfection. However, the effectors eliciting T3SS-1-independent inflammation remain to be clarified. In this study, we focused on two T3SS-2 phenotypes, macrophage proliferation and cytotoxicity, to identify the T3SS-2 effectors involved in T3SS-1-independent inflammation. We identified a mutant strain that could not induce cytotoxicity in a macrophage-like cell line and that reduced intestinal inflammation in streptomycin-pretreated mice. We also identified five T3SS-2 effectors, SifA, SpvB, SseF, SseJ, and SteA, associated with T3SS-1-independent macrophage cytotoxicity. We then constructed a strain lacking T3SS-1 and all the five T3SS-2 effectors, termed T1S5. The S. Typhimurium T1S5 strain significantly reduced cytotoxicity in macrophages in the same manner as a mutant invA spiB strain (T1T2). Finally, the T1S5 strain elicited no inflammatory changes in the ceca of streptomycin-pretreated mice. We conclude that these five T3SS-2 effectors contribute to T3SS-1-independent inflammation.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/fisiologia , Colite/microbiologia , Salmonella enterica/patogenicidade , Estreptomicina/farmacologia , Sistemas de Secreção Tipo III/fisiologia , Animais , Ceco/patologia , Colite/patologia , Modelos Animais de Doenças , Macrófagos/patologia , Camundongos , Proteínas dos Microfilamentos/fisiologia , Salmonella enterica/metabolismo
14.
Biomed Pharmacother ; 117: 109162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254739

RESUMO

Flos Abelmoschus manihot is widely used as traditional drug in China. Abelmoschus manihot (AM) extracted from Flos Abelmoschus manihot that has been applied for treating chronic inflammatory diseases. Here we showed that AM significantly alleviated DSS-induced colitis in mice. AM modified gut microbiota composition, increased microbial diversity, and in particularly, elevated the abundance of short chain fatty acids (SCFAs)-producing gut microbiota in colitic mice. Consequently, levels of SCFAs especially butyrate and acetate were increased upon AM treatment, which, primarily through peroxisome proliferator-activated receptor gamma (PPARγ) pathway, led to the enhanced Treg generation and the suppressed Th17 development. Together, we herein provide the first evidences to support that AM, a natural plant-derived complex, can potentially reset gut microbiome and metabolism, resume immune and tissue homeostasis, and hence prevent colitis, which may provide a new perspective on IBD pathogenesis and suggest a novel microbiota-targeting therapy for inflammatory gut diseases.


Assuntos
Abelmoschus/química , Colite/tratamento farmacológico , Colite/microbiologia , Microbioma Gastrointestinal , Extratos Vegetais/uso terapêutico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Bactérias/metabolismo , Diferenciação Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/imunologia , Colo/patologia , Sulfato de Dextrana , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase , Inflamação/patologia , Camundongos Endogâmicos BALB C , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos
15.
Immunology ; 158(1): 19-34, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31215020

RESUMO

Studies with gene-deficient and gnotobiotic mice have identified many host and microbial factors that contribute to induced colitis, but information on whether specific factors determine susceptibility under more physiological conditions is lacking. Using wild-type strains that differ in their IgA response but harbor a diverse gut microbiome, we found that the IgA-high strain CBA/CaJ (CBA) is resistant to acute colitis induced with dextran sodium sulfate (DSS), unlike the IgA-low strain C57BL/6 (B6). Resistance was associated with extensive IgA-coating of fecal bacteria, lower fecal bacterial loads and greater abundance of barrier-protective transcripts in colonic tissues under homeostatic conditions. Fecal microbial transplant (FT) experiments revealed that disease induction in B6 mice was associated with a cohort of bacteria that are not targeted by IgA. However, CBA mice continued to be resistant to colitis induction following FTs from B6 mice, indicating that they are able to contain such colitogenic members. In support of a role for bacterial exclusion in resistance, oral administration of immunoglobulins decreased DSS-induced disease in B6 mice. In F1 mice derived separately with CBA and B6 dams and in F1 mice backcrossed to the two parental strains, resistance segregated with the IgA response of the pups and not with barrier-associated transcripts or bacterial loads. Interestingly, B6 pups foster-nursed on CBA dams continued to be susceptible in later life, whereas CBA pups foster-nursed on B6 dams continued to be resistant. Together, the data indicate that a high-IgA response in adult life can protect against colitis and compensate for IgA deficiency in early life.


Assuntos
Bactérias/imunologia , Colite/prevenção & controle , Colo/microbiologia , Sulfato de Dextrana , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/imunologia , Animais , Animais Recém-Nascidos , Carga Bacteriana , Colite/induzido quimicamente , Colite/imunologia , Colite/microbiologia , Colo/imunologia , Colo/metabolismo , Cruzamentos Genéticos , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Imunoglobulina A/metabolismo , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lactação , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Permeabilidade , Gravidez , Especificidade da Espécie
16.
Cells ; 8(6)2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212833

RESUMO

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.


Assuntos
Anti-Inflamatórios/uso terapêutico , Microbioma Gastrointestinal , Glutationa Transferase/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colite/induzido quimicamente , Colite/microbiologia , Colite/prevenção & controle , Colite/terapia , Doença de Crohn/microbiologia , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Humanos , Imunização , Imunomodulação , Camundongos Endogâmicos BALB C , Fenótipo , Ácido Trinitrobenzenossulfônico
17.
Mol Med Rep ; 20(1): 25-32, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115531

RESUMO

Faecalibacterium prausnitzii is one of the most abundant bacteria in the human gut microbiota. This bacterium is reported to serve an important role in inflammatory bowel diseases. In the present study, the preventive effects of F. prausnitzii on a dextran sodium sulfate (DSS)­induced colitis model in mice were investigated. BALB/c mice were fed with 5% DSS in drinking water. Administration of live or inactivated F. prausnitzii was initiated 7 days prior to the start of DSS feeding. Mucosal cytokines were analyzed by reverse transcription­quantitative PCR. Histological analysis of colon mucosa was also performed. The symptoms of DSS­induced colitis (weight loss, diarrhea, bloody stools and colon shortening) were significantly improved in the group administered live F. prausnitzii, but not in the other groups. There were no significant differences in the expression of proinflammatory cytokines; however, the expression of mucosal cytokines appeared to be markedly reduced in the live F. prausnitzii­administered group compared with the DSS­fed control. The results suggested that preventive administration of 'live', but not inactivated, F. prausnitzii protected the colon against DSS­induced colitis. Live F. prausnitzii were also administered therapeutically following the induction of colitis, resulting in an improved histological score in mice.


Assuntos
Colite/microbiologia , Colite/terapia , Faecalibacterium prausnitzii/metabolismo , Microbioma Gastrointestinal/genética , Animais , Colite/induzido quimicamente , Colite/genética , Citocinas/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Água Potável/administração & dosagem , Água Potável/microbiologia , Regulação da Expressão Gênica , Humanos , Mucosa Intestinal/microbiologia , Camundongos
18.
Talanta ; 200: 537-546, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036220

RESUMO

Liquid chromatography-mass spectrometry based profiling of microbial metabolites has been a challenging task due to their diverse physicochemical properties and wide concentration ranges. This study is aimed to develop a systematic platform for the broad-scale profiling of microbial metabolites by integrating aqueous-lipophilic biphasic extractions and chemical derivatizations with a data-dependent automatable metabolite annotation algorithm. This complementary strategy of detection will not only largely expand the metabolite coverage, but also facilitate the drawing out of interested submetabolome using designed chemical derivatizations. Then, the data-dependent metabolite annotation algorithm is able to automatically match the raw MS/MS data with those of compounds in the self-collected databases. The performance of this platform is illustrated through the analysis of two representative bacteria (Escherichia coli and Pseudomonas aeruginosa) and intestinal contents samples from experimental colitis mice. As a result, 292 metabolites corresponding to 875 annotated features distributing over 25 chemical families were putatively annotated in a short time. Of these metabolites, 197 and 218 are respectively from the bacteria and intestinal contents, and 107 are identified in all three biological samples. This systematic platform could be used to accomplete high-coverage detection and high-quality data processing of microbial metabolites. At the same time, chemical derivatization design and the establishment of self-collected databases will facilitate self-driven untargeted analysis.


Assuntos
Colite/metabolismo , Escherichia coli/metabolismo , Pseudomonas aeruginosa/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Colite/induzido quimicamente , Colite/microbiologia , Sulfato de Dextrana , Espectrometria de Massas , Camundongos
19.
Infect Immun ; 87(7)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036600

RESUMO

Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in this PTS and measured bacterial growth and PTS gene expression in minimal medium supplemented with selected carbohydrates. We show that E. faecalis upregulates OG1RF_12399 transcription specifically in the presence of gluconate and that E. faecalis strains lacking, or harboring a single point mutation in, OG1RF_12399-12402 are unable to grow in minimal medium containing gluconate. We colonized germfree wild-type and colitis-prone interleukin-10-deficient mice with defined bacterial consortia containing the E. faecalis strains and measured inflammation and bacterial abundance in the colon. We infected macrophage and intestinal epithelial cell lines with the E. faecalis strains and measured intracellular bacterial survival and proinflammatory cytokine secretion. The presence of OG1RF_12399-12402 is not required for E. faecalis colonization of the mouse intestine but is associated with an accelerated onset of experimental colitis in interleukin-10-deficient mice, altered bacterial composition in the colon, enhanced E. faecalis survival within macrophages, and increased proinflammatory cytokine secretion by colon tissue and macrophages. Further studies of bacterial carbohydrate metabolism in general, and E. faecalis PTS-gluconate in particular, during inflammation may identify new mechanisms of disease pathogenesis.


Assuntos
Proteínas de Bactérias/metabolismo , Colite/microbiologia , Enterococcus faecalis/enzimologia , Macrófagos/imunologia , Fosfotransferases/metabolismo , Animais , Proteínas de Bactérias/genética , Colite/genética , Colite/imunologia , Enterococcus faecalis/genética , Enterococcus faecalis/crescimento & desenvolvimento , Feminino , Gluconatos/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Macrófagos/microbiologia , Masculino , Camundongos , Óperon , Fosfotransferases/genética
20.
J Med Microbiol ; 68(7): 978-985, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31136296

RESUMO

PURPOSE: Biofilm formation and resistance to last-line antibiotics have restricted chemotherapy options toward infection eradication. METHODOLOGY: Fifty K. oxytoca isolates were collected from patients with antibiotic-associated haemorrhagic colitis (AAHC). Antibiotic susceptibility tests were conducted and phenotypic biofilm formation was assessed using microtitre tissue plate (MTP) assay. PCR was employed to amplify the adhesins, extended-spectrum ß-lactamases (ESBLs), carbapenemase and colistin resistance genes. The expression of adhesin genes was evaluated using quantitative real-time PCR (RT-qPCR).Results/Key findings. The previous antibiotic consumption and hospitalization (P<0.05) and older ages (P=0.0033) were significantly associated with AAHC. None of the isolates produced biofilm strongly, but 70% of them produced moderate-level biofilm. The blaCTX-M (12/14), the blaIMP (8/14 MICIMI =4 µg ml-1 ) and blaOXA-48-like (5/14) and mcr-1 (4/14) genes were predominant, three of which harbouring all the genes. The expression of matB (0.023) and mrkA (0.011) was significantly different between multidrug-resistant and susceptible isolates. Furthermore, moderately biofilm producer isolates significantly exhibited higher expression of fimA (P=.0117), pilQ (P=0.002) and mrkA (P=0.020) genes compared to biofilm non-producers. No significant difference regarding gene expression was observed among ESBL alleles. CONCLUSION: Bacterial attachment by adhesins and biofilm formation among extensive drug-resistant K. oxytoca isolates hinder the efficient infection eradication. Hence, control and surveillance studies should be performed and other therapeutic auspicious approaches must be taken into account against AAHC, biofilm formation and drug resistance spread. Furthermore, previous antibiotic consumption and long-term hospitalization should be controlled.


Assuntos
Adesinas Bacterianas/metabolismo , Biofilmes/crescimento & desenvolvimento , Colite/microbiologia , Hemorragia Gastrointestinal/microbiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Klebsiella oxytoca/metabolismo , Adesinas Bacterianas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Colite/patologia , Fezes/microbiologia , Feminino , Hemorragia Gastrointestinal/patologia , Humanos , Lactente , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/genética , Klebsiella oxytoca/fisiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
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