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1.
Life Sci ; 289: 120243, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34922941

RESUMO

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 51A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 51A at a concentration of 1 × 109 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 51A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 51A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 51A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias , Irinotecano/efeitos adversos , Mucosite , Probióticos/farmacologia , Animais , Feminino , Enteropatias/induzido quimicamente , Enteropatias/microbiologia , Enteropatias/terapia , Irinotecano/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Mucosite/microbiologia , Mucosite/terapia
2.
Anim Sci J ; 92(1): e13619, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34409681

RESUMO

Heat stress in poultry is deleterious to productive performance. Chlorogenic acid (CGA) exerts antibacterial, anti-inflammatory, and antioxidant properties. This study was conducted to evaluate the effects of dietary supplemental CGA on the intestinal health and cecal microbiota composition of young hens challenged with acute heat stress. 100-day-old Hy-line brown pullets were randomly divided into four groups. The control group (C) and heat stress group (HS) received a basal diet. HS + CGA300 group and HS + CGA600 group received a basal diet supplemented with 300- and 600-mg/kg CGA, respectively, for 2 weeks before heat stress exposure. Pullets of HS, HS + CGA300 , and HS + CGA600 group were exposed to 38°C for 4 h while the control group was maintained at 25°C. In this study, dietary CGA supplementation had effect on mitigate the decreased T-AOC and T-SOD activities and the increasing of IL-1ß and TNFα induced by acute heat stress. Dietary supplementation with 600 mg/kg CGA had better effect on increasing the relative abundance of beneficial bacterial genera, such as Rikenellaceae RC9_gut_group, Ruminococcaceae UCG-005, and Christensenellaceae R-7_group, and deceasing bacteria genera involved in inflammation, such as Sutterella species. Therefore, CGA can ameliorate acute heat stress damage through suppressing inflammation and improved antioxidant capacity and cecal microbiota composition.


Assuntos
Antioxidantes/metabolismo , Ácido Clorogênico/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais , Microbioma Gastrointestinal , Transtornos de Estresse por Calor/dietoterapia , Transtornos de Estresse por Calor/veterinária , Enteropatias/dietoterapia , Enteropatias/veterinária , Microbiota , Doenças das Aves Domésticas/dietoterapia , Doenças das Aves Domésticas/microbiologia , Doença Aguda , Animais , Galinhas , Feminino , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/microbiologia , Inflamação , Enteropatias/metabolismo , Enteropatias/microbiologia , Doenças das Aves Domésticas/metabolismo
3.
J Zoo Wildl Med ; 52(2): 638-647, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130407

RESUMO

To determine the diagnostic value of fecal bacterial enteric pathogen cultures (FBEPC) as part of routine preventive medicine protocols in terrestrial mammals housed in a zoological collection, this study investigated the clinical utility of FBEPC results in context of subsequent clinical actions and how its use was rationalized after adjunct use of fecal cytology as a first-line diagnostic tool. Retrospective results (n = 692) that included a routine FBEPC panel of a commercial diagnostic laboratory, including Aeromonas, Salmonella, Campylobacter, Plesiomonas, Shigella, Yersinia, and Edwardsiella, of 417 mammals were organized into preventive (P; n = 485), diagnostic (D; n = 177), or recheck (R; n = 30) samples; for P and D samples, findings were assigned a "clinical significance factor" of 1 to 5 according to culture results and subsequent clinical actions. A score of 3 or higher indicated positive growth of potentially pathogenic bacterial organisms, of which there were 50 FBEPC (P n = 27, D n = 20, R n = 3). The difference in mean clinical significance factor for P versus D samples was significant. Aeromonas spp. were most frequently isolated (n = 32), followed by Salmonella spp. (n = 8) and Plesiomonas shigelloides (n = 8), then Campylobacter spp. (n = 5). There was no growth of Yersinia enterocolitica, Shigella spp., or Edwardsiella spp. In the absence of clinical evidence of gastrointestinal disease, treatment was initiated in only two cases with isolated Campylobacter spp. Implementation of fecal cytology as an initial step in fecal evaluation resulted in a prompt, substantial reduction in number of ordered FBEPC (mean n = 12/month before and n = 5/month after implementation). The findings in this study suggest that FBEPC for these bacterial species has limited value as a screening tool in preventive medicine protocols for the mammalian orders best represented in this study. The use of fecal cytology led to a more targeted and cost-effective use of FBEPC. Fecal cytology as an initial step in preventative and diagnostic testing protocols is recommended.


Assuntos
Animais de Zoológico , Bactérias/isolamento & purificação , Infecções Bacterianas/veterinária , Fezes/microbiologia , Enteropatias/veterinária , Mamíferos , Animais , Bactérias/classificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Fezes/citologia , Enteropatias/diagnóstico , Enteropatias/microbiologia , Estudos Retrospectivos
4.
Am J Gastroenterol ; 116(4): 780-787, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33982948

RESUMO

INTRODUCTION: The North American Consensus guidelines for glucose breath testing (GBT) for small intestinal bacterial overgrowth (SIBO) incorporated changes in glucose dosing and diagnostic cutoffs. We compared GBT positivity based on hydrogen and methane excretion and quantified symptoms during performance of the North American vs older modified Rome Consensus protocols. METHODS: GBT was performed using the North American protocol (75 g glucose, cutoffs >20 parts per million [ppm] hydrogen increase after glucose and >10 ppm methane anytime) in 3,102 patients vs modified Rome protocol (50 g glucose, >12 ppm hydrogen and methane increases after glucose) in 3,193 patients with suspected SIBO. RESULTS: Positive GBT were more common with the North American vs modified Rome protocol (39.5% vs 29.7%, P < 0.001). Overall percentages with GBT positivity using methane criteria were greater and hydrogen criteria lower with the North American protocol (P < 0.001). Peak methane levels were higher for the North American protocol (P < 0.001). Times to peak hydrogen and methane production were not different between protocols. With the North American protocol, gastrointestinal and extraintestinal symptoms were more prevalent after glucose with both positive and negative GBT (P < 0.04) and greater numbers of symptoms (P < 0.001) were reported. DISCUSSION: GBT performed using the North American Consensus protocol was more often positive for SIBO vs the modified Rome protocol because of more prevalent positive methane excretion. Symptoms during testing were greater with the North American protocol. Implications of these observations on determining breath test positivity and antibiotic decisions for SIBO await future prospective testing.


Assuntos
Infecções Bacterianas/diagnóstico , Testes Respiratórios/métodos , Consenso , Glucose/farmacologia , Enteropatias/diagnóstico , Intestino Delgado/microbiologia , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Feminino , Humanos , Hidrogênio/análise , Enteropatias/metabolismo , Enteropatias/microbiologia , Masculino , Metano/análise , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Front Immunol ; 12: 644982, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815399

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many hematological disorders and autoimmune diseases, but acute graft-versus-host disease (aGVHD) has remained a major obstacle that limits allo-HSCT and exhibits a daunting mortality rate. The gastrointestinal system is among the most common sites affected by aGVHD. Experimental advances in the field of intestinal microbiota research enhanced our understanding - not only of the quantity and diversity of intestinal microbiota - but also their association with homeostasis of the immune system and disease pathogenesis, including that of aGVHD. Meanwhile, ever-growing clinical evidence suggest that the intestinal microbiota is dysregulated in patients who develop aGVHD and that the imbalance may affect clinical outcomes, indicating a potential predictive role for microbiota dysregulation in aGVHD severity and prognosis. The current animal and human studies investigating the intestinal microbiota in aGVHD and the understanding of the influence and management of the microbiota in the clinic are reviewed herein. Taken together, monitoring and remodeling the intestinal microecology following allo-HSCT may provide us with promising avenues for diagnosing, preventing or treating aGVHD in the clinic.


Assuntos
Microbioma Gastrointestinal/imunologia , Doença Enxerto-Hospedeiro , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Enteropatias , Intestinos , Animais , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/microbiologia , Doença Enxerto-Hospedeiro/mortalidade , Doenças Hematológicas/imunologia , Doenças Hematológicas/microbiologia , Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Humanos , Enteropatias/imunologia , Enteropatias/microbiologia , Enteropatias/mortalidade , Intestinos/imunologia , Intestinos/microbiologia , Transplante Homólogo
6.
Nutrients ; 13(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809940

RESUMO

Small intestinal bacterial overgrowth (SIBO) occurs commonly, is difficult to treat, and frequently recurs. Bovine colostrum (BC) and chicken eggs contain immunoglobulins and other components that possess antimicrobial, immunoregulatory, and growth factor activities; however, it is not known if they have the ability to reduce injury caused by the presence of bacteria associated with SIBO (Streptococcus, Escherichia coli, Staphylococcus, Bacteroides, Klebsiella, Enterococcus, and Proteus) and infectious diarrhea (enteropathogenic Escherichia coli, Salmonella). We examined the effects of BC, egg, or the combination, on bacterial growth and bacteria-induced changes in transepithelial electrical resistance (TEER) and bacterial translocation across confluent Caco-2 monolayers. BC, egg, or the combination did not affect bacterial growth. Adding bacteria to monolayers reduced TEER and (with minor variations among species) increased bacterial translocation, increased monolayer apoptosis (increased caspase-3 and Baxα, reduced Bcl2), increased intercellular adhesion molecule 1 (ICAM-1), and reduced cell adhesion molecules zonulin1 (ZO1) and claudin-1. BC, egg, or the combination reduced these effects (all p < 0.01) and caused additional increases in vascular endothelial growth factor (VEGF) and Heat Shock Protein 70 (Hsp70) expression. We conclude that BC ± egg strengthens mucosal integrity against a battery of bacteria relevant for SIBO and for infectious diarrhea. Oral BC ± egg may have clinical value for these conditions, especially SIBO where eradication of precipitating organisms may be difficult to achieve.


Assuntos
Infecções Bacterianas/complicações , Colostro/metabolismo , Disenteria/tratamento farmacológico , Disenteria/etiologia , Intestino Delgado/microbiologia , Óvulo/metabolismo , Animais , Infecções Bacterianas/tratamento farmacológico , Células CACO-2 , Bovinos , Humanos , Técnicas In Vitro , Enteropatias/tratamento farmacológico , Enteropatias/etiologia , Enteropatias/microbiologia
7.
Int J Mol Sci ; 22(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801524

RESUMO

Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions' attack by pathogens, including bacteria, viruses, fungi, and parasites.


Assuntos
Bactérias/patogenicidade , Células Epiteliais/fisiologia , Infecções/fisiopatologia , Enteropatias/fisiopatologia , Mucosa Intestinal/fisiologia , Junções Íntimas/fisiologia , Animais , Permeabilidade da Membrana Celular , Humanos , Infecções/microbiologia , Enteropatias/microbiologia , Transdução de Sinais
8.
Nutrients ; 13(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803197

RESUMO

Fibrosis is a severe complication of chronic inflammatory disorders, such as inflammatory bowel disease (IBD). Current strategies are not fully effective in treating fibrosis; therefore, innovative anti-fibrotic approaches are urgently needed. TGF-ß1 plays a central role in the fibrotic process by inducing myofibroblast differentiation and excessive extracellular matrix (ECM) protein deposition. Here, we explored the potential anti-fibrotic impact of two high concentration multi-strain probiotic formulations on TGF-ß1-activated human intestinal colonic myofibroblast CCD-18Co. Human colonic fibroblast CCD-18Co cells were cultured in the presence of TGF-ß1 to develop a fibrotic phenotype. Cell viability and growth were measured using the Trypan Blue dye exclusion test. The collagen-I, α-SMA, and pSmad2/3 expression levels were evaluated by Western blot analysis. Fibrosis markers were also analyzed by immunofluorescence and microscopy. The levels of TGF-ß1 in the culture medium were assessed by ELISA. The effects of commercially available probiotic products VSL#3® and Vivomixx® were evaluated as the soluble fraction of bacterial lysates. The results suggested that the soluble fraction of Vivomixx® formulation, but not VSL#3®, was able to antagonize the pro-fibrotic effects of TGF-ß1 on CCD-18Co cells, being able to prevent all of the cellular and molecular parameters that are related to the fibrotic phenotype. The mechanism underlying the observed effect appeared to be associated with inhibition of the TGF-ß1/Smad signaling pathway. To our knowledge, this study provides the first experimental evidence that Vivomixx® could be considered to be a promising candidate against intestinal fibrosis, being able to antagonize TGF-ß1 pro-fibrotic effects. The differences that were observed in our fibrosis model between the two probiotics used could be attributable to the different number of strains in different proportions.


Assuntos
Extratos Celulares/farmacologia , Doenças Inflamatórias Intestinais/microbiologia , Enteropatias/prevenção & controle , Intestinos/patologia , Probióticos/química , Diferenciação Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Humanos , Doenças Inflamatórias Intestinais/complicações , Enteropatias/microbiologia , Enteropatias/patologia , Intestinos/microbiologia , Miofibroblastos/efeitos dos fármacos , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo
10.
J Leukoc Biol ; 109(3): 519-533, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33630384

RESUMO

In 1908, Ilya Metchnikov, then Assistant director of the Pasteur Institute, writes about the potential of bacterial cultures to remedy a range of intestinal ailments. Translated from French.


Assuntos
Bactérias/metabolismo , Enteropatias/microbiologia , Enteropatias/terapia , Intestinos/microbiologia , Animais , Pesquisa Empírica , História do Século XX , Humanos , Leite/microbiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-33571672

RESUMO

Butyrate, propionate, and acetate are short-chain fatty acids (SCFAs) mainly produced by bacterial metabolism in the human gut after dietary fiber intake. SCFAs are considered important for health maintenance by promoting lipid, glucose, and immune homeostasis with an adequate composition of intestinal microbiota, including other beneficial effects like providing protection against colorectal cancer. Therapies with exogenous SCFAs have been proposed to reduce inflammation in intestinal diseases that result from SCFA dysbiosis and cause mucosal inflammation. The aim of this mini-review was to provide an overview of the importance of SCFAs on metabolic and inflammatory processes as well as their role in treating chronic inflammatory disorders.


Assuntos
Bactérias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Enteropatias/metabolismo , Enteropatias/microbiologia , Metabolismo dos Lipídeos , Glucose/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/microbiologia
12.
AAPS J ; 23(2): 32, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629139

RESUMO

As one of the most important metabolites of vitamin A, all-trans retinoic acid (RA) plays a crucial role in regulating immune responses. RA has been shown to promote the differentiation of naïve T and B cells and perform diverse functions in the presence of different cytokines. RA also induces gut tropic lymphocytes through upregulating the expression of chemokine (C-C motif) receptor 9 (CCR9) and α4ß7 integrin. In addition, RA promotes the expression of the enzyme retinal dehydrogenase (RALDH) on dendritic cells, which in turn strengthens the ability to synthesize RA. Due to the insolubility of RA, proper formulation design can maximize its ability to improve immune responses for vaccines. Recent studies have developed some formulations co-loading RA and antigen, which can effectively imprint lymphocytes gut homing properties and induce intestine immune responses as well as systemic responses through parenteral administration, providing a promising direction for the protection against mucosal infections. Here, we review the mechanism and effects of RA on lymphocyte differentiation and gut homing, and recent progress of RA delivery systems to improve mucosal immune responses.


Assuntos
Portadores de Fármacos/química , Imunidade nas Mucosas/efeitos dos fármacos , Enteropatias/prevenção & controle , Tretinoína/administração & dosagem , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Humanos , Imunogenicidade da Vacina , Enteropatias/imunologia , Enteropatias/microbiologia , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Camundongos , Solubilidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Tretinoína/química , Tretinoína/imunologia , Excipientes de Vacinas/química , Vacinas/química , Vacinas/imunologia
13.
Int J Mol Sci ; 22(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573273

RESUMO

After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and change their physicochemical properties upon modification by gut bacteria, and vice versa, BAs also shape the composition and function of the intestinal microbiota. This mutual interplay of both BAs and gut microbiota regulates many physiological processes, including the lipid, carbohydrate and energy metabolism of the host. Emerging evidence also implies an important role of this enterohepatic BA circuit in shaping mucosal colonization resistance as well as local and distant immune responses, tissue physiology and carcinogenesis. Subsequently, disrupted interactions of gut bacteria and BAs are associated with many disorders as diverse as Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson's disease, schizophrenia and epilepsy. As we cannot address all of these interesting underlying pathophysiologic mechanisms here, we summarize the current knowledge about the physiologic and pathogenic interplay of local site microbiota and the enterohepatic BA metabolism using a few selected examples of liver and gut diseases.


Assuntos
Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/fisiologia , Enteropatias/metabolismo , Hepatopatias/metabolismo , Animais , Metabolismo dos Carboidratos/fisiologia , Modelos Animais de Doenças , Metabolismo Energético/fisiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Enteropatias/imunologia , Enteropatias/microbiologia , Enteropatias/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Metabolismo dos Lipídeos/fisiologia , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/imunologia , Hepatopatias/microbiologia , Hepatopatias/patologia
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(1): 94-100, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33461259

RESUMO

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.


Assuntos
Microbioma Gastrointestinal , Enteropatias , Hepatopatias , Fígado/fisiopatologia , Nutrição Parenteral/efeitos adversos , Síndrome do Intestino Curto/fisiopatologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/fisiopatologia , Ácidos e Sais Biliares/fisiologia , Colestase/etiologia , Colestase/microbiologia , Colestase/fisiopatologia , Nutrição Enteral , Microbioma Gastrointestinal/fisiologia , Humanos , Enteropatias/etiologia , Enteropatias/microbiologia , Enteropatias/fisiopatologia , Intestinos/microbiologia , Intestinos/fisiologia , Intestinos/fisiopatologia , Fígado/microbiologia , Fígado/fisiologia , Hepatopatias/etiologia , Hepatopatias/microbiologia , Hepatopatias/fisiopatologia , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/dietoterapia , Transdução de Sinais
15.
PLoS Pathog ; 17(1): e1009191, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465156

RESUMO

The immunological impact of individual commensal species within the microbiota is poorly understood limiting the use of commensals to treat disease. Here, we systematically profile the immunological fingerprint of commensals from the major phyla in the human intestine (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria) to reveal taxonomic patterns in immune activation and use this information to rationally design commensal communities to enhance antibacterial defenses and combat intestinal inflammation. We reveal that Bacteroidetes and Firmicutes have distinct effects on intestinal immunity by differentially inducing primary and secondary response genes. Within these phyla, the immunostimulatory capacity of commensals from the Bacteroidia class (Bacteroidetes phyla) reflects their robustness of TLR4 activation and Bacteroidia communities rely solely on this receptor for their effects on intestinal immunity. By contrast, within the Clostridia class (Firmicutes phyla) it reflects the degree of TLR2 and TLR4 activation, and communities of Clostridia signal via both of these receptors to exert their effects on intestinal immunity. By analyzing the receptors, intracellular signaling components and transcription factors that are engaged by different commensal species, we identify canonical NF-κB signaling as a critical rheostat which grades the degree of immune stimulation commensals elicit. Guided by this immunological analysis, we constructed a cross-phylum consortium of commensals (Bacteroides uniformis, Bacteroides ovatus, Peptostreptococcus anaerobius and Clostridium histolyticum) which enhances innate TLR, IL6 and macrophages-dependent defenses against intestinal colonization by vancomycin resistant Enterococci, and fortifies mucosal barrier function during pathological intestinal inflammation through the same pathway. Critically, the setpoint of intestinal immunity established by this consortium is calibrated by canonical NF-κB signaling. Thus, by profiling the immunological impact of major human commensal species our work paves the way for rational microbiota reengineering to protect against antibiotic resistant infections and to treat intestinal inflammation.


Assuntos
Bactérias/imunologia , Inflamação/prevenção & controle , Enteropatias/prevenção & controle , Mucosa Intestinal/imunologia , Animais , Bactérias/classificação , Bactérias/metabolismo , Feminino , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Enteropatias/imunologia , Enteropatias/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Filogenia , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
16.
Vet Microbiol ; 252: 108924, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33203576

RESUMO

Shiga toxin-producing E. coli (STEC) and enterotoxigenic E. coli (ETEC) are the main agents of swine colibacillosis, an infectious disease which implies important economic losses. We characterized here 186 diarrheagenic E. coli from Spanish industrial pig farms (2005-2017) to know which clones were involved in this syndrome, and the rates of antibiotic resistance. The PCR based on pathotype-associated virulence genes determined that 161 of 186 isolates (86.5 %) exhibited the ETEC pathotype, 10 (5.4 %) the STEC pathotype, and 15 (8.1 %) the hybrid ETEC/STEC pathotype. The majority of the isolates showed phylogroup A (85.5 %), clonotype CH11-24 (72 %) and belonged to the clonal complex (CC) 10, including two ETEC clones accounting for around 50 % of the 186 isolates: O157:HNM-A-ST10 (CH11-24), which exhibited mostly the fimbrial antigen F4ac; and O108:HNM-A-ST10 (CH11-24), which exhibited mainly F18. Other associations were O139:H1-E-ST1 (CH2-54) with the STEC pathotype, and both O141:H4-A-CC10 (CH11-24) and O138:HNM-E-ST42 (CH28-41) with ETEC/STEC. We found that 87.1 % of the isolates were multidrug-resistant, including 9% ESBL-producers, with the highest rates to nalidixic acid (82 %), colistin (77 %), ticarcillin (76 %) and ampicillin (76 %). Besides, more than 50 % of isolates showed non-susceptibility to gentamicin, tobramycin, doxycycline, ciprofloxacin, trimethoprim-sufamethoxazole and chloramphenicol. Additionally, 11 out of 17 ESBL-producing isolates were mcr-carriers. Results suggest that O108:HNM-A-ST10 (CH11-24) F18 is an emerging clone taking space left by other classical serogroups. Further follow-up studies on predominant clones in pig colibacillosis are essential for the update of vaccines, as alternative to the use of antibiotics.


Assuntos
Farmacorresistência Bacteriana/genética , Escherichia coli Enterotoxigênica/genética , Infecções por Escherichia coli/veterinária , Enteropatias/veterinária , Escherichia coli Shiga Toxigênica/genética , Doenças dos Suínos/microbiologia , Animais , Antibacterianos/farmacologia , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Enteropatias/microbiologia , Enteropatias/patologia , Filogenia , Sorogrupo , Escherichia coli Shiga Toxigênica/isolamento & purificação , Espanha/epidemiologia , Suínos , Doenças dos Suínos/patologia , Virulência/genética
17.
Curr Opin Nephrol Hypertens ; 30(1): 75-84, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148949

RESUMO

PURPOSE OF REVIEW: Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Interventions aimed at restoring gut microbiota have emerged as a potential therapeutic option in CKD. This review summarizes the current evidence on gut microbiota-targeted strategies in patients with CKD. RECENT FINDINGS: A growing number of studies have shown that plant-based diets, low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment may lead to favorable alterations in the gut microbiota. Current evidence suggests that the implementation of both plant-based and low-protein diets has potential benefits for the primary prevention of CKD, and for slowing CKD progression, with minimal risk of hyperkalemia and/or cachexia. The use of prebiotics, probiotics, and synbiotics and laxatives may have beneficial effects on uremic toxin generation, but their evidence is limited for the prevention and treatment of CKD. Recent advances in diagnostic technologies (e.g., high-throughput sequencing and nanotechnology) could enhance rapid diagnosis, monitoring, and design of effective therapeutic strategies for mitigating gut dysbiosis in CKD. SUMMARY: Plant-based and low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment represent novel gut microbiota-targeted strategies in the conservative management of CKD, which could improve clinical outcomes in CKD.


Assuntos
Constipação Intestinal , Disbiose , Microbioma Gastrointestinal , Enteropatias , Insuficiência Renal Crônica , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Dieta com Restrição de Proteínas , Dieta Vegetariana , Progressão da Doença , Disbiose/complicações , Disbiose/diagnóstico , Disbiose/microbiologia , Disbiose/terapia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Humanos , Enteropatias/complicações , Enteropatias/diagnóstico , Enteropatias/microbiologia , Enteropatias/terapia , Laxantes/uso terapêutico , Nanotecnologia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/terapia , Simbióticos/administração & dosagem , Uremia/etiologia , Uremia/terapia
18.
Immunology ; 162(3): 281-289, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33314083

RESUMO

The NOD-like receptor family pyrin domain containing 6 (NLRP6), a member of the NOD-like receptor (NLR) family, acts as a cytosolic innate immune sensor that recognizes microbe-associated molecular patterns. In some circumstances upon activation, NLRP6 recruits the adaptor apoptosis-associated speck-like protein (ASC) and the inflammatory caspase-1 or caspase-11 to form an inflammasome, which mediates the maturation and secretion of the pro-inflammatory cytokines IL-18 and IL-1ß. In other contexts, NLRP6 can exert its function in an inflammasome-independent manner. Tight regulation of the NLRP6 inflammasome is critical in maintaining tissue homeostasis, while improper inflammasome activation may contribute to the development of multiple diseases. In intestinal epithelial cells, the NLRP6 inflammasome is suggested to play a role in regulating gut microbiome composition, goblet cell function and related susceptibility to gastrointestinal inflammatory, infectious and neoplastic diseases. Additionally, NLRP6 may regulate extra-intestinal diseases. In this review, we summarize current knowledge on the NLRP6 inflammasome and its activation and regulation patterns, as well as its effector functions contributing to disease modulation. We discuss current challenges in NLRP6 research and future prospects in harnessing its function into potential human interventions.


Assuntos
Imunidade Inata , Inflamassomos/metabolismo , Enteropatias/metabolismo , Mucosa Intestinal/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Microbioma Gastrointestinal , Humanos , Inflamassomos/genética , Enteropatias/genética , Enteropatias/imunologia , Enteropatias/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transdução de Sinais
19.
J Appl Microbiol ; 131(1): 470-484, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33289241

RESUMO

AIMS: This study evaluated the effects of Bacillus amyloliquefaciens TL106, isolated from Tibetan pigs' faeces, on the growth performance, immune response, intestinal barrier function, morphology of jejunum, caecum and colon, and gut microbiota in the mice with enterohaemorrhagic Escherichia coli (EHEC)-induced intestinal diseases. METHODS AND RESULTS: In all, 40 female C57BL/6J mice were randomly divided into four groups: mice fed a normal diet (Control), mice oral administration of TL106 daily (Ba), mice challenged with EHEC O157:H7 on day 15 (O157) and mice oral administration of TL106 daily and challenged with EHEC O157:H7 on day 15 (Ba+O157). The TL106 was administrated to mice for 14 days, and mice were infected with O157:H7 at day 15. We found that TL106 could prevent the weight loss caused by O157:H7 infection and alleviated the associated increase in pro-inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-8) and decrease in anti-inflammatory factor (IL-10) in serum and intestinal tissues of mice caused by O157:H7 infection (P < 0·05). Additionally, TL106 could prevent disruption of gut morphology caused by O157:H7 infection, and alleviate the associated decrease in expression of tight junction proteins (ZO-1, occludin and claudin-1) in jejunum and colon (P < 0·05). In caecum and colon, the alpha diversity for bacterial community analysis of Chao and ACE index in Ba+O157 group were higher than O157 group. The TL106 stabilized gut microbiota disturbed by O157:H7, including increasing Lachnospiraceae, Prevotellaceae, Muribaculaceae and Akkermansiaceae, and reducing Lactobacillaceae. CONCLUSIONS: We indicated the B. amyloliquefaciens TL106 can effectively protect mice against EHEC O157:H7 infection by relieving inflammation, improving intestinal barrier function, mitigating permeability disruption and stabilizing the gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus amyloliquefaciens TL106 can prevent and treat intestinal disease induced by EHEC O157:H7 in mice, which may be a promising probiotic for disease prevention in animals.


Assuntos
Bacillus amyloliquefaciens/fisiologia , Infecções por Escherichia coli/terapia , Escherichia coli O157/efeitos dos fármacos , Enteropatias/terapia , Animais , Bacillus amyloliquefaciens/isolamento & purificação , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Enteropatias/imunologia , Enteropatias/metabolismo , Enteropatias/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Probióticos/farmacologia , Probióticos/uso terapêutico , Suínos
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