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1.
Nutrients ; 13(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34959740

RESUMO

Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients.


Assuntos
Colite/microbiologia , Colite/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Magnésio/farmacologia , Animais , Colite/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/terapia , Fezes/microbiologia , Feminino , Deficiência de Magnésio/microbiologia , Deficiência de Magnésio/terapia , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S
2.
Nutrients ; 13(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684320

RESUMO

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease. Probiotics have a potential beneficial effect on the prevention of UC onset and relapse in clinical trials. Lactobacillus rhamnosus GG (L. rhamnosus GG) have shown clinical benefits on UC patients, however, the precise mechanisms are unknown. The aim of this study is to explore the effect of extracellular vesicles released from L. rhamnosus GG (LGG-EVs) on dextran sulfate sodium (DSS)-induced colitis and propose the underlying mechanism of LGG-EVs for protecting against colitis. The results showed that LGG-EVs could prevent colonic tissue damage and shortening of the colon (p < 0.01), and ameliorate intestinal inflammation by inhibiting TLR4-NF-κB-NLRP3 axis activation. Consistently, the pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-2) were suppressed effectively upon LGG-EVs treatment (p < 0.05). The 16S rRNA sequencing showed that LGG-EVs administration could reshape the gut microbiota in DSS-induced colitis mice, which further alters the metabolism pathways of gut microbiota. These findings propose a novel perspective of L. rhamnosus GG in attenuating inflammation mediated by extracellular vesicles and offer consideration for developing oral gavage of LGG-EVs for colitis therapies.


Assuntos
Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Inflamação/microbiologia , Lactobacillus rhamnosus/metabolismo , Animais , Biodiversidade , Colite/induzido quimicamente , Colite/genética , Colite/microbiologia , Colite/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Vesículas Extracelulares/ultraestrutura , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/imunologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Especificidade de Órgãos , Análise de Componente Principal
3.
Nutrients ; 13(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684567

RESUMO

Commonly used synthetic dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate-80 (P80), promote intestinal inflammation. We compared abilities of CMC vs. P80 to potentiate colitis and impact human microbiota in an inflammatory environment using a novel colitis model of ex-germ-free (GF) IL10-/- mice colonized by pooled fecal transplant from three patients with active inflammatory bowel diseases. After three days, mice received 1% CMC or P80 in drinking water or water alone for four weeks. Inflammation was quantified by serial fecal lipocalin 2 (Lcn-2) and after four weeks by blinded colonic histologic scores and colonic inflammatory cytokine gene expression. Microbiota profiles in cecal contents were determined by shotgun metagenomic sequencing. CMC treatment significantly increased fecal Lcn-2 levels compared to P80 and water treatment by one week and throughout the experiment. Likewise, CMC treatment increased histologic inflammatory scores and colonic inflammatory cytokine gene expression compared with P80 and water controls. The two emulsifiers differentially affected specific intestinal microbiota. CMC did not impact bacterial composition but significantly decreased Caudoviricetes (bacteriophages), while P80 exposure non-significantly increased the abundance of both Actinobacteria and Proteobacteria. Commonly used dietary emulsifiers have different abilities to induce colitis in humanized mice. CMC promotes more aggressive inflammation without changing bacterial composition.


Assuntos
Carboximetilcelulose Sódica/efeitos adversos , Colite/induzido quimicamente , Colite/microbiologia , Emulsificantes/efeitos adversos , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Polissorbatos/efeitos adversos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Colite/patologia , Colo/metabolismo , Colo/patologia , Fezes/microbiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
4.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360835

RESUMO

Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, Bifidobacterium, is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify Bifidobacterium species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway.


Assuntos
Bifidobacterium bifidum/fisiologia , Colite/microbiologia , Mucosa Intestinal/microbiologia , Transdução de Sinais , Junções Íntimas , Receptor 2 Toll-Like/metabolismo , Animais , Células CACO-2 , Colite/prevenção & controle , Humanos , Mucosa Intestinal/metabolismo , Camundongos , NF-kappa B , Permeabilidade , Probióticos
5.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445403

RESUMO

Natural smectites have demonstrated efficacy in the treatment of diarrhea. The present study evaluated the prophylactic effect of a diosmectite (FI5pp) on the clinical course, colon damage, expression of tight junction (TJ) proteins and the composition of the gut microbiota in dextran sulfate sodium (DSS) colitis. Diosmectite was administered daily to Balb/c mice from day 1 to 7 by oral gavage, followed by induction of acute DSS-colitis from day 8 to 14 ("Control", n = 6; "DSS", n = 10; "FI5pp + DSS", n = 11). Mice were sacrificed on day 21. Clinical symptoms (body weight, stool consistency and occult blood) were checked daily after colitis induction. Colon tissue was collected for histological damage scoring and quantification of tight junction protein expression. Stool samples were collected for microbiome analysis. Our study revealed prophylactic diosmectite treatment attenuated the severity of DSS colitis, which was apparent by significantly reduced weight loss (p = 0.022 vs. DSS), disease activity index (p = 0.0025 vs. DSS) and histological damage score (p = 0.023 vs. DSS). No significant effects were obtained for the expression of TJ proteins (claudin-2 and claudin-3) after diosmectite treatment. Characterization of the microbial composition by 16S amplicon NGS showed that diosmectite treatment modified the DSS-associated dysbiosis. Thus, diosmectites are promising candidates for therapeutic approaches to target intestinal inflammation and to identify possible underlying mechanisms of diosmectites in further studies.


Assuntos
Bactérias/classificação , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Microbiota/efeitos dos fármacos , Silicatos/administração & dosagem , Administração Oral , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , DNA Bacteriano/genética , DNA Ribossômico/genética , Fezes/microbiologia , Masculino , Camundongos Endogâmicos BALB C , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Índice de Gravidade de Doença , Silicatos/farmacologia , Proteínas de Junções Íntimas/metabolismo , Resultado do Tratamento
6.
Front Immunol ; 12: 683911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354704

RESUMO

Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.


Assuntos
Autofagia/efeitos dos fármacos , Colite/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Panax/química , Polissacarídeos/farmacologia , Animais , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Citocinas/metabolismo , Transplante de Microbiota Fecal , Feminino , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Serina-Treonina Quinases TOR/metabolismo
7.
Nature ; 596(7870): 114-118, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34262174

RESUMO

Pathogenic fungi reside in the intestinal microbiota but rarely cause disease. Little is known about the interactions between fungi and the immune system that promote commensalism. Here we investigate the role of adaptive immunity in promoting mutual interactions between fungi and host. We find that potentially pathogenic Candida species induce and are targeted by intestinal immunoglobulin A (IgA) responses. Focused studies on Candida albicans reveal that the pathogenic hyphal morphotype, which is specialized for adhesion and invasion, is preferentially targeted and suppressed by intestinal IgA responses. IgA from mice and humans directly targets hyphal-enriched cell-surface adhesins. Although typically required for pathogenesis, C. albicans hyphae are less fit for gut colonization1,2 and we show that immune selection against hyphae improves the competitive fitness of C. albicans. C. albicans exacerbates intestinal colitis3 and we demonstrate that hyphae and an IgA-targeted adhesin exacerbate intestinal damage. Finally, using a clinically relevant vaccine to induce an adhesin-specific immune response protects mice from C. albicans-associated damage during colitis. Together, our findings show that adaptive immunity suppresses harmful fungal effectors, with benefits to both C. albicans and its host. Thus, IgA uniquely uncouples colonization from pathogenesis in commensal fungi to promote homeostasis.


Assuntos
Imunidade Adaptativa , Candida albicans/imunologia , Candida albicans/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Simbiose/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos de Fungos/imunologia , Candida albicans/patogenicidade , Colite/imunologia , Colite/microbiologia , Colite/patologia , Feminino , Vacinas Fúngicas/imunologia , Microbioma Gastrointestinal/imunologia , Humanos , Hifas/imunologia , Imunoglobulina A/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto Jovem
8.
Int J Nanomedicine ; 16: 4545-4557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267512

RESUMO

Background: Shigella infection has always been a global burden, and it particularly threatens children between the ages of 1 and 5 years. Economically underdeveloped countries are dominated by Shigella flexneri infection. The most effective method to treat Shigella is antibiotics, but with the abuse of antibiotics and the prevalence of multidrug resistance, we urgently need a relatively safe non-antibiotic treatment to replace it. Ultrasmall Au nanoclusters (NCs) have special physical and chemical properties and can better interact with and be internalized by bacteria to disrupt the metabolic balance. The purpose of this study was to explore whether Au NCs may be a substitute for antibiotics to treat Shigella infections. Methods: Au NCs and Shigella Sf301, R2448, and RII-1 were cocultured in vitro to evaluate the bactericidal ability of Au NCs. The degree of damage and mode of action of Au NCs in Shigella were clearly observed in images of scanning electron microscopy (SEM). In vivo experiments were conducted to observe the changes in body weight, clinical disease activity index (DAI) and colon (including length and histopathological sections) of mice treated with Au NCs. The effect of Au NCs was analysed by measuring the content of lipocalin-2 (LCN2) and Shigella in faeces. Next, the changes in Shigella biofilm activity, the release of reactive oxygen species (ROS), the changes in metabolism-related and membrane-related genes, and the effect of Au NCs on the body weight of mice were determined to further analyse the mechanism of action and effect. Results: Au NCs (100 µM) interfered with oxidative metabolism genes, induced a substantial increase in ROS levels, interacted with the cell membrane to destroy it, significantly killed Shigella, and effectively alleviated the intestinal damage caused by Shigella in mice. The activity of the biofilm formed by Shigella was reduced. Conclusion: The effective antibacterial effect and good safety suggest that Au NCs represent a good potential alternative to antibiotics to treat Shigella infections.


Assuntos
Colite/metabolismo , Colite/microbiologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Shigella/fisiologia , Animais , Colite/tratamento farmacológico , Ouro/uso terapêutico , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Shigella/efeitos dos fármacos
9.
J Exp Med ; 218(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34287641

RESUMO

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.


Assuntos
Proteína Forkhead Box O1/metabolismo , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/fisiologia , Muco/metabolismo , Animais , Autofagia/fisiologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Disbiose/genética , Ácidos Graxos Voláteis/metabolismo , Feminino , Proteína Forkhead Box O1/genética , Células Caliciformes/patologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Mucina-2/metabolismo , Simbiose/fisiologia
10.
Front Immunol ; 12: 677870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220823

RESUMO

Background: 16S sequencing results are often used for Machine Learning (ML) tasks. 16S gene sequences are represented as feature counts, which are associated with taxonomic representation. Raw feature counts may not be the optimal representation for ML. Methods: We checked multiple preprocessing steps and tested the optimal combination for 16S sequencing-based classification tasks. We computed the contribution of each step to the accuracy as measured by the Area Under Curve (AUC) of the classification. Results: We show that the log of the feature counts is much more informative than the relative counts. We further show that merging features associated with the same taxonomy at a given level, through a dimension reduction step for each group of bacteria improves the AUC. Finally, we show that z-scoring has a very limited effect on the results. Conclusions: The prepossessing of microbiome 16S data is crucial for optimal microbiome based Machine Learning. These preprocessing steps are integrated into the MIPMLP - Microbiome Preprocessing Machine Learning Pipeline, which is available as a stand-alone version at: https://github.com/louzounlab/microbiome/tree/master/Preprocess or as a service at http://mip-mlp.math.biu.ac.il/Home Both contain the code, and standard test sets.


Assuntos
Bactérias/classificação , Bactérias/genética , Colite/microbiologia , Microbioma Gastrointestinal/genética , Aprendizado de Máquina , Mucosite/microbiologia , Adulto , Animais , Colite/metabolismo , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Interleucina-1alfa/metabolismo , Camundongos , Mucosite/metabolismo , Redes Neurais de Computação , Filogenia , Gravidez , Progesterona/metabolismo , RNA Ribossômico 16S/genética
11.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209042

RESUMO

BACKGROUND AND AIMS: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. METHODS: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). RESULTS: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. CONCLUSIONS: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.


Assuntos
Compostos Férricos/administração & dosagem , Compostos Férricos/farmacologia , Compostos Ferrosos/farmacologia , Pironas/administração & dosagem , Pironas/farmacologia , Administração Oral , Animais , Biodiversidade , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Sulfato de Dextrana , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Ferro/metabolismo , Camundongos Endogâmicos C57BL , Filogenia
12.
Front Immunol ; 12: 648341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093536

RESUMO

Behçet's disease (BD) is a multisystem autoinflammatory condition characterized by mucosal ulceration, breakdown of immune privilege sites and vasculitis. A genetic basis for BD has been described in genome-wide and validation studies. Similarly, dysbiosis of oral and gut microbiomes have been associated with BD. This review will describe links between genetic polymorphisms in genes encoding molecules involved in gut biology and changes seen in microbiome studies. A potential decrease in bacterial species producing short chain fatty acids linked to mutations in genes involved in their production suggests a potential therapy for BD.


Assuntos
Síndrome de Behçet/genética , Síndrome de Behçet/microbiologia , Disbiose/genética , Microbioma Gastrointestinal/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Animais , Bactérias/metabolismo , Síndrome de Behçet/imunologia , Butiratos/metabolismo , Butiratos/uso terapêutico , Colite/tratamento farmacológico , Colite/imunologia , Colite/microbiologia , Modelos Animais de Doenças , Disbiose/imunologia , Disbiose/metabolismo , Ácidos Graxos Voláteis/metabolismo , Humanos , Camundongos , Mutação , Resultado do Tratamento
13.
Sci Rep ; 11(1): 13485, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188111

RESUMO

Viral triggers at the intestinal mucosa can have multiple global effects on intestinal integrity, causing elevated intestinal barrier strength and relative protection from subsequent inflammatory bowel disease (IBD) induction in various models. As viruses can interfere with the intestinal immune system both directly and indirectly through commensal bacteria, cause-effect relationships are difficult to define. Due to the complexity of putatively causative factors, our understanding of such virus-mediated protection is currently very limited. We here set out to better understand the impact that adult enteric infection with rotavirus (RV) might have on the composition of the intestinal microbiome and on the severity of IBD. We found that RV infection neither induced significant long-lasting microbiota community changes in the small or large intestine nor affected the severity of subsequent dextran sulfate sodium-induced colitis. Hence, adult murine RV infection does not exert lasting effects on intestinal homeostasis.


Assuntos
Colite/microbiologia , Microbioma Gastrointestinal , Infecções por Rotavirus , Rotavirus/metabolismo , Animais , Colite/induzido quimicamente , Sulfato de Dextrana/toxicidade , Suscetibilidade a Doenças , Feminino , Camundongos , Infecções por Rotavirus/metabolismo , Infecções por Rotavirus/microbiologia
15.
Int J Biol Macromol ; 182: 2024-2036, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087293

RESUMO

In this study, ramulus mori polysaccharide (RMP) was encapsulated into Poly (lactic-co-glycolicacid) (PLGA) to form PLGA-RMP (PR). The aim of study is to investigate anti-inflammatory effects of PR. The particle size of PR nanoparticles was approximately 205.6 ± 1.86 nm. PR nanoparticles showed significant therapeutic effects on colitis mice model, evidenced by attenuation of the loss of body weight, reduction of the DAI score, and restoration of the colon length. From the histopathological analysis, alleviation of the histopathological damage, less production of IFN-γ and IL-6, and improvement of IL-10 were observed with the treatment of PR. Meanwhile, the treatment of PR not only promoted the expression of ZO-1 and occludin, but also improved the contents of acetate, propionate, and butyrate in the colitis colon. Furthermore, PR extenuated the reduction of the diversity and richness of gut microbiota induced by DSS, and decreased the ratio of Firmicutes to Bacteroidetes while increasing the proportion of Clostridium XIVa, Mucispirillum, and Paraprevotella in the gut microbiota. What's more, PR nanoparticles attenuated the metabolic disorders in the colitis colon induced by DSS. These results indicated that PR nanoparticles could serve as a potent nanomedicine to treat IBD and be used as potential prebiotics.


Assuntos
Anti-Inflamatórios/farmacologia , Morus/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polissacarídeos/uso terapêutico , Eletricidade Estática , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia
16.
Elife ; 102021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085924

RESUMO

The composition of gut-associated microbial communities changes during intestinal inflammation, including an expansion of Enterobacteriaceae populations. The mechanisms underlying microbiota changes during inflammation are incompletely understood. Here, we analyzed previously published metagenomic datasets with a focus on microbial hydrogen metabolism. The bacterial genomes in the inflamed murine gut and in patients with inflammatory bowel disease contained more genes encoding predicted hydrogen-utilizing hydrogenases compared to communities found under non-inflamed conditions. To validate these findings, we investigated hydrogen metabolism of Escherichia coli, a representative Enterobacteriaceae, in mouse models of colitis. E. coli mutants lacking hydrogenase-1 and hydrogenase-2 displayed decreased fitness during colonization of the inflamed cecum and colon. Utilization of molecular hydrogen was in part dependent on respiration of inflammation-derived electron acceptors. This work highlights the contribution of hydrogenases to alterations of the gut microbiota in the context of non-infectious colitis.


Assuntos
Ceco/microbiologia , Colite/induzido quimicamente , Colite/microbiologia , Colo/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/metabolismo , Microbioma Gastrointestinal , Hidrogênio/metabolismo , Animais , Ceco/metabolismo , Ceco/patologia , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Bases de Dados Genéticas , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Hidrogenase/genética , Hidrogenase/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Metagenoma , Metagenômica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piroxicam
17.
Biomolecules ; 11(5)2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063522

RESUMO

The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs' persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.


Assuntos
Colite/prevenção & controle , Colo/metabolismo , Escherichia coli/metabolismo , Inflamação/prevenção & controle , Lactobacillus/metabolismo , Probióticos/farmacologia , Animais , Terapia Biológica/métodos , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Escherichia coli/isolamento & purificação , Feminino , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Lactobacillus/isolamento & purificação , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL
18.
Sci Rep ; 11(1): 9841, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972615

RESUMO

Findings from gut microbiome studies are strongly influenced by both experimental and analytical factors that can unintentionally bias their interpretation. Environment is also critical. Both co-housing and maternal effects are expected to affect microbiomes and have the potential to confound other manipulated factors, such as genetics. We therefore analysed microbiome data from a mouse experiment using littermate controls and tested differences among genotypes (wildtype versus colitis prone-mdr1a-/-), gut niches (stool versus mucus), host ages (6 versus 18 weeks), social groups (co-housed siblings of different genotypes) and maternal influence. We constructed a 16S phylogenetic tree from bacterial communities, fitting random forest models using all 428,234 clades identified. Models discriminated all criteria except host genotype, where no community differences were found. Host social groups differed in abundant, low-level, taxa whereas intermediate phylogenetic and abundance scales distinguished ages and niches. Thus, a carefully controlled experiment treating evolutionary clades of microbes equivalently without reference to taxonomy, clearly identifies whether and how gut microbial communities are distinct across ecologically important factors (niche and host age) and other experimental factors, notably cage effects and maternal influence. These findings highlight the importance of considering such environmental factors in future microbiome studies.


Assuntos
Colite/microbiologia , Microbioma Gastrointestinal , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Fatores Etários , Animais , Colite/genética , Colo/microbiologia , DNA Bacteriano/isolamento & purificação , Modelos Animais de Doenças , Fezes/microbiologia , Humanos , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Knockout , Filogenia , RNA Ribossômico 16S/genética
19.
Nat Immunol ; 22(6): 699-710, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34040226

RESUMO

It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes are unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic but not bone marrow-derived macrophages, which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early-life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later-life susceptibility or resistance to iNKT cell-associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota, and they reveal an important postnatal function of macrophages that emerge in fetal life.


Assuntos
Colite/imunologia , Mucosa Intestinal/imunologia , Listeriose/imunologia , Macrófagos/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Animais , Proliferação de Células/genética , Colite/microbiologia , Colite/patologia , Colo/citologia , Colo/embriologia , Colo/imunologia , Colo/patologia , Citocinas/metabolismo , Toxina Diftérica/administração & dosagem , Toxina Diftérica/imunologia , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Vida Livre de Germes , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/embriologia , Mucosa Intestinal/patologia , Listeriose/microbiologia , Listeriose/patologia , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , RNA-Seq , Transdução de Sinais/genética , Transdução de Sinais/imunologia
20.
Am J Med Sci ; 362(2): 188-197, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33932348

RESUMO

BACKGROUND: The abnormalities of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are implicated in various autoimmune disorders and tumors. This study investigated the influence of TRAIL deficiency on Th17 cells and colonic microbiota in experimental colitis mouse model. METHODS: Mice were randomly divided into 4 groups: wild-type, TRAIL gene knock-out (TRAIL-/-), wild-type colitis and TRAIL-/- colitis groups. Colitis was induced by oral administration of 3.5% dextran sulfate sodium (DSS) for 7 consecutive days. Mice were given scores for disease severity both clinically and histopathologically. Th17 cells in peripheral blood and mesenteric lymph nodes (MLNs) were assessed using flow cytometry. The expression levels of Th17 cell markers IL-17A and ROR-γt were evaluated by quantitative real-time polymerase chain reaction. The colonic samples were also analyzed for microbiota profile by 16s-rDNA gene sequencing on variable V4 region. RESULTS: Compared with wild-type counterparts, TRAIL-/- mice developed more severe colitis after DSS treatment. Colitis TRAIL-/- mice had increased proportion of Th17 cells and elevated mRNA expression levels of IL-17A and ROR-γt in peripheral blood and MLNs compared with colitis wild-type mice. In contrast to colitis wild-type mice, the composition of colonic microbiota was shifted in colitis TRAIL-/- mice, and was characterized by increased alpha diversity, increased TM7, deferribacteres and tenericutes, and decreased proteobacteria at the phylum level. CONCLUSIONS: These findings suggested that TRAIL deficiency not only aggravated DSS-induced colitis, but also led to enhanced Th17 cell response and altered colonic microbiota composition.


Assuntos
Colite/induzido quimicamente , Colo/microbiologia , Microbioma Gastrointestinal , Ligante Indutor de Apoptose Relacionado a TNF/deficiência , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Ligante Indutor de Apoptose Relacionado a TNF/genética , Células Th17
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