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1.
Sci Rep ; 12(1): 19609, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380080

RESUMO

Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.


Assuntos
Disbiose , Lentinano , Camundongos , Animais , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Disbiose/metabolismo , Lentinano/farmacologia , Antibacterianos/efeitos adversos , Firmicutes/metabolismo , Bacteroidetes/metabolismo , Proteínas de Junções Íntimas , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Camundongos Endogâmicos C57BL
2.
Cell Host Microbe ; 30(10): 1450-1463.e8, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36228585

RESUMO

Abdominal aortic aneurysm (AAA) is an insidious and lethal vascular disease that lacks effective nonsurgical interventions. Gut microbiota dysbiosis plays key roles in many diseases, but its relationship with AAA has not been fully elucidated. Herein, we reveal significant abnormalities in the gut microbe composition of AAA patients and confirm that gut microbiota dysbiosis is an important cause of AAA. Specifically, R. intestinalis was significantly reduced in AAA patients. Using AAA mice, we show that R. intestinalis and its metabolite butyrate significantly reduce neutrophil infiltration and NOX2-dependent neutrophil extracellular trap formation, inflammation, and abnormal phenotypic switching of vascular smooth muscle cells in the aortic wall, thereby markedly alleviating AAA development. Our research uncovers the role and mechanism of the gut microbiota in AAA development and provides insights into AAA prophylaxis from a microecological perspective.


Assuntos
Aneurisma da Aorta Abdominal , Armadilhas Extracelulares , Microbioma Gastrointestinal , Animais , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/prevenção & controle , Butiratos/metabolismo , Modelos Animais de Doenças , Disbiose/metabolismo , Armadilhas Extracelulares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
3.
Cancer Prev Res (Phila) ; 15(11): 755-766, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219239

RESUMO

Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. PREVENTION RELEVANCE: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.


Assuntos
Neoplasias Colorretais , Epigenoma , Humanos , Disbiose/complicações , Disbiose/genética , Disbiose/metabolismo , RNA Ribossômico 16S/genética , Metilação de DNA , Epigênese Genética , Mucosa Intestinal/patologia , Neoplasias Colorretais/patologia
4.
Ageing Res Rev ; 82: 101759, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36243356

RESUMO

Parkinson's disease (PD) is a complicated neurodegenerative disease, of which gastrointestinal disturbance appears prior to motor symptoms. Numerous studies have shed light on the roles of gastrointestinal tract and its neural connection to brain in PD pathology. In the past decades, the fields of microbiology and neuroscience have become ever more entwined. The emergence of gut microbiome has been considered as one of the key regulators of gut-brain function. With the advent of multi-omics sequencing techniques, gut microbiome of PD patients has been shown unique characteristics. The resident gut microbiota can exert considerable effects in PD and there are suggestions of a link between gut microbiome dysbiosis and PD progression. In this review, we summarize the latest progresses of gut microbiome dysbiosis in PD pathogenesis, further highlight the clinical relevance of gut microbiota and its metabolites in both the non-motor and motor symptoms of PD. Furthermore, we draw attention to the complex interplay between gut microbiota and PD drugs, with the purpose of improving drug efficacy and prescription accordingly. Further studies at specific strain level and longitudinal prospective clinical trials using optimized methods are still needed for the development of diagnostic markers and novel therapeutic regimens for PD.


Assuntos
Microbioma Gastrointestinal , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Disbiose/metabolismo , Doença de Parkinson/metabolismo , Estudos Prospectivos
5.
Nutrition ; 103-104: 111836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36202025

RESUMO

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has a growing epidemiologic and economic burden. It is associated with Western diet (WD) patterns, and its pathogenesis involves metabolic disorders (obesity, dyslipidemia, hyperglycemia, and diabetes) and gut dysbiosis, features that are usually neglected or not reproduced by most animal models. Thus, we established a 6-mo WD-induced NAFLD mouse model associated with metabolic disorder, investigating its main features at the gut microbiome-liver-adipose tissue axis, also evaluating the correlations of gut dysbiosis to the other disease outcomes. METHODS: Male C57 BL6 mice received a high-fat (30% lard and 0.2% cholesterol, ∼57% calories) and sucrose-rich (20%) chow, and a high-sugar solution (23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 mo. RESULTS: The model featured high serum cholesterol levels, glucose intolerance, and hyperinsulinemia. WD intervention resulted in extensive macro/microvesicular liver steatosis and pericellular fibrosis-resembling human disease-accompanied by hepatic stellate cell activation and CD68+ macrophage infiltration, increased protein levels of proinflammatory p65-nuclear factor-κB, interleukin-6 and tumor necrosis factor-α, with decreased antioxidant regulator Nrf2. Mice showed clear obesity with adipocyte hypertrophy, and CD68+macrophage/mast cell infiltration in adipose tissue while a reduction in number of goblet cells was also observed in the small intestine. Moreover, the pyrosequencing of the 16 S ribosomal RNA of gut cecal content showed decreased bacterial diversity, enriched Firmicutes and Proteobacteria, decreased Bacteroidetes and Fusobacteria, and increased ratio of Firmicutes to Bacteroidetes. Bacteroidetes and Bacteroides had the highest number of significant correlations with liver-adipose tissue axis outcomes. In silico analysis of gut microbiome in NAFLD obese patients revealed a depletion in Bacteroides, which also correlated to disease outcomes. CONCLUSION: This mice model gathered suitable phenotypical alterations in gut-liver-adipose tissue axis that resembled NAFLD associated with metabolic disorders in humans and may be considered for preclinical investigation.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Ocidental/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Disbiose/metabolismo , Fígado/metabolismo , Obesidade/etiologia , Modelos Animais de Doenças , Tecido Adiposo/metabolismo , Bacteroides , Colesterol , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
6.
Chem Biol Interact ; 368: 110231, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36288778

RESUMO

The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.


Assuntos
Asma , Microbioma Gastrointestinal , Humanos , Disbiose/metabolismo , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/uso terapêutico , Pulmão/metabolismo , Asma/tratamento farmacológico
7.
Nutrients ; 14(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36235584

RESUMO

Plant polysaccharide intervention has shown significant potential to combat obesity. However, studies on animal polysaccharides are indeed rare. The aim of this study was to investigate the potential functions of CIP (IL) on obesity, intestinal microflora dysbiosis, and the possible protection of intestinal barrier in mice fed with high-fat diet (HFD). Our results revealed that after 13 weeks, the HFD+L (high-fat diet + 25 mg/kg CIP) group showed significantly more weight loss and fat accumulation relative to the HFD+H (high-fat diet + 50 mg/kg CIP) group. Furthermore, CIP intervention modulated lipid metabolism and mRNA levels of inflammatory mediators in liver. Overall, CIP clearly improved the intestinal barrier in HFD-fed mice. Additionally, we observed that CIP intervention improved intestinal microbiota community richness and diversity in HFD-fed mice. The CIP intervention mice group showed a relatively low Firmicutes to Bacteroidetes ratio compared to the HFD group. This study concluded that CIP could be used as a functional food to prevent adipocyte accumulation, reduce systemic inflammation, and protect the intestinal barrier.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Gelatina , Mediadores da Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Obesidade/metabolismo , Polissacarídeos/farmacologia , RNA Mensageiro
8.
Nutrients ; 14(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36235622

RESUMO

Herein we gathered updated knowledge regarding the alterations of gut microbiota (dysbiosis) and its correlation with human neurodegenerative and brain-related diseases, e.g., Alzheimer's and Parkinson's. This review underlines the importance of gut-derived metabolites and gut metabolic status as the main players in gut-brain crosstalk and their implications on the severity of neural conditions. Scientific evidence indicates that the administration of probiotic bacteria exerts beneficial and protective effects as reduced systemic inflammation, neuroinflammation, and inhibited neurodegeneration. The experimental results performed on animals, but also human clinical trials, show the importance of designing a novel microbiota-based probiotic dietary supplementation with the aim to prevent or ease the symptoms of Alzheimer's and Parkinson's diseases or other forms of dementia or neurodegeneration.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Doenças do Sistema Nervoso , Doença de Parkinson , Probióticos , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Disbiose/metabolismo , Humanos , Metaboloma , Doenças do Sistema Nervoso/metabolismo , Doença de Parkinson/metabolismo , Probióticos/uso terapêutico
9.
World J Gastroenterol ; 28(29): 3903-3916, 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-36157543

RESUMO

BACKGROUND: Chronic abdominal pain is the most common cause for gastroenterology consultation and is frequently associated with functional gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease. These disorders present similar brain/gut/microbiota trialogue alterations, associated with abnormal intestinal permeability, intestinal dysbiosis and colonic hypersensitivity (CHS). Intestinal dysbiosis can alter colon homeostasis leading to abnormal activation of the innate immunity that promotes CHS, perhaps involving the toll-like receptors (TLRs), which play a central role in innate immunity. AIM: To understand the mechanisms between early life event paradigm on intestinal permeability, fecal microbiota composition and CHS development in mice with TLRs expression in colonocytes. METHODS: Maternal separation model (NMS) CHS model, which mimics deleterious events in childhood that can induce a wide range of chronic disorders during adulthood were used. Colonic sensitivity of NMS mice was evaluated by colorectal distension (CRD) coupled with intracolonic pressure variation (IPV) measurement. Fecal microbiota composition was analyzed by 16S rRNA sequencing from weaning to CRD periods. TLR mRNA expression was evaluated in colonocytes. Additionally, the effect of acute intrarectal instillation of the TLR5 agonist flagellin (FliC) on CHS in adult naive wildtype mice was analyzed. RESULTS: Around 50% of NMS mice exhibited increased intestinal permeability and CHS associated with intestinal dysbiosis, characterized by a significant decrease of species richness, an alteration of the core fecal microbiota and a specific increased relative abundance of flagellated bacteria. Only TLR5 mRNA expression was increased in colonocytes of NMS mice with CHS. Acute intrarectal instillation of FliC induced transient increase of IPV, reflecting transient CHS appearance. CONCLUSION: Altogether, these data suggest a pathophysiological continuum between intestinal dysbiosis and CHS, with a role for TLR5.


Assuntos
Disbiose , Receptor 5 Toll-Like , Animais , Colo , Modelos Animais de Doenças , Disbiose/metabolismo , Flagelina/metabolismo , Flagelina/farmacologia , Privação Materna , Camundongos , RNA Mensageiro/metabolismo , RNA Ribossômico 16S , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Receptores Toll-Like/metabolismo
10.
Food Funct ; 13(19): 9878-9892, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36052713

RESUMO

The progression of nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance and gut microbiota. Dietary interventions have emerged as effective palliative strategies for NAFLD. The present study investigated the potential mechanisms by which α-lactalbumin peptide Asp-Gln-Trp (DQW) ameliorated insulin resistance and gut microbiota dysbiosis in high-fat diet (HFD)-induced NAFLD mice. The results demonstrated that DQW treatment alleviated HFD-induced body weight gain, hepatic steatosis, insulin resistance, and dyslipidemia. DQW treatment also increased the ratio of Bacteroides to Firmicutes in the gut, reduced the relative abundance of pathogenic bacteria (such as Bacteroides, Blautia, and Alistipes) and enhanced the relative abundance of short-chain fatty acid (SCFA)-producing bacteria (such as Muribaculaceae, Lachnospiraceae_NK4A136_group, and Rikenellaceae_RC9_gut_group). DQW treatment promoted the production of SCFAs and subsequently improved intestinal barrier integrity and inflammation. Furthermore, the results of real-time quantitative PCR (qRT-PCR) and western blotting further proved that the effects of DQW on the attenuation of hepatic insulin resistance were mediated by the PPARα and IRS1/PI3K/AKT pathways. Taken together, these results indicated that DQW treatment could attenuate HFD-induced NAFLD and insulin resistance by modulating gut microbiota composition, enhancing the SCFA levels, and activating the PPARα and IRS1/PI3K/Akt pathways.


Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/tratamento farmacológico , Disbiose/metabolismo , Ácidos Graxos Voláteis/metabolismo , Lactalbumina/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/metabolismo , Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
11.
Int J Mol Sci ; 23(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36142859

RESUMO

Although the impacts of Saccharomyces cerevisiae on cancers are mentioned, data on its use in mice with cyclic GMP-AMP synthase deficiency (cGAS-/-) are even rarer. Here, 12 weeks of oral administration of S. cerevisiae protected cGAS-/- mice from azoxymethane (AOM)-induced colon cancers, partly through dysbiosis attenuation (fecal microbiome analysis). In parallel, a daily intralesional injection of a whole glucan particle (WGP; the beta-glucan extracted from S. cerevisiae) attenuated the growth of subcutaneous tumor using MC38 (murine colon cancer cell line) in cGAS-/- mice. Interestingly, the incubation of fluorescent-stained MC38 with several subtypes of macrophages, including M1 (using Lipopolysaccharide; LPS), M2 (IL-4), and tumor-associated macrophages (TAM; using MC38 supernatant activation), could not further reduce the tumor burdens (fluorescent intensity) compared with M0 (control culture media). However, WGP enhanced tumoricidal activities (fluorescent intensity), the genes of M1 pro-inflammatory macrophage polarization (IL-1ß and iNOS), and Dectin-1 expression and increased cell energy status (extracellular flux analysis) in M0, M2, and TAM. In M1, WGP could not increase tumoricidal activities, Dectin-1, and glycolysis activity, despite the upregulated IL-1ß. In conclusion, S. cerevisiae inhibited the growth of colon cancers through dysbiosis attenuation and macrophage energy activation, partly through Dectin-1 stimulation. Our data support the use of S. cerevisiae for colon cancer protection.


Assuntos
Neoplasias do Colo , beta-Glucanas , Animais , Azoximetano , Neoplasias do Colo/metabolismo , Meios de Cultura/metabolismo , Disbiose/metabolismo , Interleucina-4/metabolismo , Lectinas Tipo C , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Nucleotidiltransferases/metabolismo , Saccharomyces cerevisiae/metabolismo , beta-Glucanas/metabolismo , beta-Glucanas/farmacologia
12.
J Agric Food Chem ; 70(39): 12629-12640, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36129345

RESUMO

Selenium-enriched black soybean protein (SeBSP) is a kind of high-quality selenium resource with many physiological functions. Benzo(a)pyrene (BaP) is a well-known injurant that widely exists in high-temperature processed food and has been previously found to cause colon injury. In this study, the effects of SeBSP on colonic damage induced by BaP in BALB/C mice were investigated by comparing it with normal black soybean protein (BSP). SeBSP inhibited the BaP-induced reductions on body weight, food intake, and water intake. Moreover, metabolic enzymes, including AhR, CYP1A1, CYP1B1, and GST-P1, that were promoted by BaP were downregulated by SeBSP, reducing oxidative damage caused by BaP in the metabolic process. The classical pyroptosis indexes (i.e., NLRP3, ASC, Caspase-1, GSDMD) and inflammatory factors (i.e., TNF-α, IL-1ß, IL-18, iNOS, COX-2) were downregulated by SeBSP in BaP-treated mice, suggesting the benefits of SeBSP in reducing colonic toxicity. Notably, SeBSP enhanced microbial diversity of gut microbiota and increased relative abundances of prebiotic bacteria, for example, Lactobacillus reuteri, Bacteroides thetaiotaomicron, and genera Bifidobacterium, and Blautia, along with the promotion of short-chain fatty acids. Integrative analysis showed strong links between the antioxidant and anti-inflammatory effects of SeBSP and its altered gut microbiota. Collectively, our study demonstrates the pronounced benefits of Se-enriched black soybean in preventing the colonic toxicity of BaP, and such effects could be mediated by gut microbiota.


Assuntos
Benzo(a)pireno , Selênio , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Benzo(a)pireno/metabolismo , Caspases/metabolismo , Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Disbiose/metabolismo , Interleucina-18/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Selênio/metabolismo , Proteínas de Soja/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Orv Hetil ; 163(32): 1261-1267, 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35933621

RESUMO

Obesity is a combination of genetic, environmental factors, and systemic inflammation of adipose tissue. In the last decade, more and more evidence suggests that intestinal microbiota is an environmental factor that plays a crucial role in obesity and associated metabolic disorders. Here, we review the association between intestinal microbiota and obesity based on the literature data available to us. The intestinal flora, in the equilibrium state of conventional bacteria, protects the health of the host and helps the development of the immune system. The genome, diet, lifestyle, and epigenetic changes of the host can pathologically alter the composition of the microbiota. In dysbiosis, the development of the gut-associated lymphoid tissue (GALT) associated with the intestinal tract is impaired and the integrity of the intestinal barrier is impaired. Due to the consequent intestinal hyperpermeability, components of pathogenic pathogens such as lipopolysaccharides enter the bloodstream. These components bind to receptors on adipose tissue immune cells as ligands for molecular samples with pathogenic properties and induce adipose tissue dysfunction. The secretion of inflammatory cytokines in adipose tissue is increased. This induces persistent low chronic inflammation, which is responsible for the development of obesity. The damage to health caused by the hyperpermeability of the intestinal barrier can be reduced by interventions, or restored early in the process. Knowing the relationships will help prevent and treat obesity. Orv Hetil. 2022; 163(32): 1261-1267.


Assuntos
Disbiose , Microbioma Gastrointestinal , Disbiose/complicações , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Inflamação , Intestinos/microbiologia , Obesidade/metabolismo
14.
Front Immunol ; 13: 960488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967376

RESUMO

Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of disease pathology. HS is characterized by aberrant activation of the innate immune system, resulting in activation of pathways that aim to protect against pathogenic microorganisms, and also contribute to failure to resolve inflammation. Imbalance in innate immunity is evident in deregulation of host antimicrobial peptides (AMPs) and the complement system associated with the microbiome dysbiosis. The pathology is further complicated by ability of pathogens associated with HS to overcome host immune response. Potential roles of major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 and complement proteins are discussed. Dysregulated expression pattern of innate immunity components in conjunction with bacterial component of the disease warrants consideration of novel treatment approaches targeting both host immunity and pathogenic microbiome in HS.


Assuntos
Hidradenite Supurativa , Proteínas do Sistema Complemento/metabolismo , Disbiose/metabolismo , Hidradenite Supurativa/patologia , Humanos , Imunidade Inata , Inflamação/metabolismo , Pele
15.
J Ethnopharmacol ; 298: 115647, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987415

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is pathologically characterized by an immune response accommodative insufficiency and dysbiosis accompanied by persistent epithelial barrier dysfunction, and is divided into ulcerative colitis (UC) and Crohn's disease (CD). Its progression increases the susceptibility to colitis-associated cancer (CAC), as well as other complications. The Xiao-Jian-Zhong (XJZ) formula has a historical application in the clinic to combat gastrointestinal disorders. AIM OF THE STUDY: The investigation aimed to explore the molecular and cellular mechanisms of XJZ. MATERIALS AND METHODS: Dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for a week to establish murine models of experimental colitis, and the XJZ solution was administered for two weeks. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of XJZ against UC and CAC. 16S rRNA sequencing and untargeted metabolomics were conducted utilizing murine feces to examine the changes in the microbiome profile. Biochemical experiments were conducted to confirm the predicted functions. RESULTS: XJZ treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis, predicted by network pharmacology analysis. Based on The Cancer Genome Atlas (TCGA) database, the XJZ-targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in cancer intervention. Moreover, the XJZ therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and reversed the declined linoleic acid metabolism and increased cytochrome P450 activity in murine colitis models. Our in-vitro experiments confirmed that the XJZ treatment suppressed Caspase1-dependent pyroptosis and increased peroxisome proliferators-activated receptor-γ(PPAR-γ) expression in the colon, facilitated the alternative activation of macrophages (Mφs), inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs), thereby favoring the mucosal healing. CONCLUSION: The XJZ formula is efficacious for colitis by a prompt resolution of inflammation and dysbiosis, and by re-establishing a microbiome profile that favors re-epithelization, and prevents carcinogenesis.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose/metabolismo , Inflamação/patologia , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Farmacologia em Rede , RNA Ribossômico 16S
17.
Mucosal Immunol ; 15(6): 1321-1337, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35999460

RESUMO

Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show that deletion of IκBζ in IECs in mice leads to dysbiosis with marked expansion of segmented filamentous bacteria (SFB), thereby enhancing Th17 cell development and exacerbating inflammatory diseases. Mechanistically, the IκBζ deficiency results in decrease in the number of Paneth cells and impairment in expression of IL-17-inducible genes involved in IgA production. The decrease in Paneth cells is caused by aberrant activation of IFN-γ signaling and a failure of IL-17-dependent recovery from IFN-γ-induced damage. Thus, the IL-17R-IκBζ axis in IECs contributes to the maintenance of intestinal homeostasis by serving as a key component in a regulatory loop between the gut microbiota and immune cells.


Assuntos
Interleucina-17 , Células Th17 , Camundongos , Animais , Interleucina-17/genética , Interleucina-17/metabolismo , Células Epiteliais , Disbiose/metabolismo , Celulas de Paneth/metabolismo , Expressão Gênica , Mucosa Intestinal
18.
J Agric Food Chem ; 70(29): 9026-9038, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35833673

RESUMO

The fungal microbiota may be involved in the regulation of cognition and behavior, while the role of probiotic fungi against cognitive impairment is unclear. Here, we explored the idea that probiotic Saccharomyces boulardii could participate in the regulation of microglia-induced neuroinflammation in Alzheimer's disease (AD) model mice. Cognitive deficits, deposits of amyloid-ß (Aß) and phosphorylation of tau, synaptic plasticity, microglia activation, and neuroinflammatory reactions were observed. The expression levels of Toll-like receptors (TLRs) pathway-related proteins were detected. Meanwhile, intestinal barrier integrity and fungal microbiota composition were evaluated. Our results showed fungal microbiota dysbiosis in APP/PS1 mice, which might result in the neuroinflammation of AD. The increased levels of interleukin (IL)-6, IL-1ß, and cluster of differentiation 11b (CD11b) were observed in APP/PS1 mice, which were associated with activation of microglia, indicative of a broader recognition of neuroinflammation mediated by fungal microbiota compared to hitherto appreciated. Probiotic S. boulardii treatment improved dysbiosis, alleviated the neuroinflammation as well as synaptic injury, and ultimately improved cognitive impairment. Moreover, S. boulardii therapy could inhibit microglia activation and the TLRs pathway, which were reversed by antifungal treatment. These findings revealed that S. boulardii actively participated in regulating the TLRs pathway to inhibit the neuroinflammation via the gut-brain axis.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Micobioma , Probióticos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Eixo Encéfalo-Intestino , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Disbiose/metabolismo , Fungos/metabolismo , Camundongos , Camundongos Transgênicos , Microglia
19.
Theranostics ; 12(11): 5204-5219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836813

RESUMO

Background: Inflammatory bowel disease (IBD) involves complicated crosstalk between host immunity and the gut microbiome, whereas the mechanics of how they govern intestinal inflammation remain poorly understood. In this study, we investigated the contribution of environmental factors to shaping gut microbiota composition in colitis mice that were transgenic for human IL-37, a natural anti-inflammatory cytokine possessing pathogenic and protective functions related to microbiota alterations. Methods: Mice transgenic expressing human IL-37 (IL-37tg) were housed under conventional and specific pathogen-free (SPF) conditions to develop a mouse model of dextran sulfate sodium (DSS)-induced colitis. 16S ribosomal RNA sequencing was used for analyzing fecal microbial communities. The efficacy of microbiota in the development of colitis in IL-37tg mice was investigated after antibiotic treatment and fecal microbiota transplantation (FMT). The mechanism by which IL-37 worsened colitis was studied by evaluating intestinal epithelial barrier function, immune cell infiltration, the expression of diverse cytokines and chemokines, as well as activated signaling pathways. Results: We found that IL-37 overexpression aggravated DSS-induced colitis in conventional mice but protected against colitis in SPF mice. These conflicting results from IL-37tg colitis mice are ascribed to a dysbiosis of the gut microbiota in which detrimental bacteria increased in IL-37tg conventional mice. We further identified that the outcome of IL-37-caused colon inflammation is strongly related to intestinal epithelial barrier impairment caused by pathogenic bacteria, neutrophils, and NK cells recruitment in colon lamina propria and mesenteric lymph node to enhance inflammatory responses in IL-37tg conventional mice. Conclusions: The immunoregulatory properties of IL-37 are detrimental in the face of dysbiosis of the intestinal microbiota, which contributes to exacerbated IBD occurrences that are uncontrollable by the immune system, suggesting that depleting gut pathogenic bacteria or maintaining intestinal microbial and immune homeostasis could be a promising therapeutic strategy for IBD.


Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Bactérias , Colite/patologia , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Disbiose/metabolismo , Humanos , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
20.
Adv Drug Deliv Rev ; 188: 114418, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35787390

RESUMO

The gut microbiota came into focus within the last years regarding being associated with or even underlying neuropsychiatric diseases. The existence of the gut-brain-axis makes it highly plausible that bacterial metabolites or toxins that escape the intestinal environment or approach the vagal connections towards the brain, exert devastating effects on the central nervous system. In Alzheimer's disease (AD), growing evidence for dysbiotic changes in the gut microbiota is obtained, even though the question for cause or consequence remains open. Nevertheless, using modulation of microbiota to address inflammatory processes seems an attractive therapeutic approach as certain microbial products such as short chain fatty acids have been proven to exert beneficial cognitive effects. In this review, we summarize, contemporary knowledge on neuroinflammation and inflammatory processes within the brain and even more detailed in the gut in AD, try to conclude whom to target regarding human microbial commensals and report on current interventional trials.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Microbiota , Probióticos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Neuroinflamatórias , Probióticos/uso terapêutico
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