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1.
Zool Res ; 41(1): 20-31, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31930784

RESUMO

There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3 + T, CD4 + T, and CD16 + NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20 + B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.


Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal , Intestinos/anatomia & histologia , Macaca mulatta/microbiologia , Animais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , DNA Bacteriano/genética , Fezes/microbiologia , Intestinos/microbiologia , Masculino
2.
J Agric Food Chem ; 68(5): 1237-1247, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31722525

RESUMO

Alcoholic liver injury, known as the most general result of chronic alcohol intake, is induced by inflammatory responses, which is activated by intestine-derived endotoxins formed from intestinal dysbiosis. The hepatoprotective activity of rice bran phenolic extract (RBPE) on ethanol-fed mice was investigated for the first time in this study, and the underlying mechanism was explored from gut microbiota, barrier function, and hepatic inflammation. Mice were fed an alcohol-containing liquid diet alone or in mixture with RBPE for 8 weeks. RBPE treatment mitigated ethanol-induced liver damage, evidenced by the declined lipid profile levels and hepatic function markers. Moreover, ethanol intake induced intestinal microbiota dysbiosis, which was attenuated by RBPE supplementation. RBPE treatment improved the alcohol-induced decrease in the expression of ZO-1, Claudin-1, Claudin-4, and Reg3g, revealing the ameliorative effect of RBPE on intestinal barrier dysfunction. Furthermore, RBPE treatment repressed the alcohol-induced trigger of the hepatic endotoxin-TLR4-NF-κB pathway, followed by the mitigated liver inflammation. The findings indicate that RBPE supplementation ameliorates intestinal microbiota dysbiosis and barrier dysfunction, inactivates the endotoxin-TLR4-NF-κB pathway, and represses inflammatory responses in liver, and therefore, intake of RBPE or brown rice may be an effective way to mitigate alcoholic liver injury.


Assuntos
Disbiose/tratamento farmacológico , Mucosa Intestinal/microbiologia , Hepatopatias Alcoólicas/prevenção & controle , NF-kappa B/imunologia , Oryza/química , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Receptor 4 Toll-Like/imunologia , Animais , Disbiose/genética , Disbiose/imunologia , Disbiose/microbiologia , Endotoxinas/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Substâncias Protetoras/administração & dosagem , Receptor 4 Toll-Like/genética
3.
Gut ; 69(1): 42-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036757

RESUMO

BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Imunidade Adaptativa , Adulto , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/imunologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Feminino , Seguimentos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/imunologia , Masculino , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos
4.
World J Gastroenterol ; 25(39): 5897-5917, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660028

RESUMO

Portal hypertension (PHT) in advanced chronic liver disease (ACLD) results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition (structural component) and intrahepatic vasoconstriction (functional component). PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding. Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns (PAMPs) that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways. Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability: The intestinal barrier function is affected by impaired microcirculation, neoangiogenesis, and abnormal vascular and mucosal permeability. The close bidirectional relationship between the gut and the liver has been termed "gut-liver axis". Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function, intestinal barrier integrity, as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects. The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments, however, further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed. In this review, we summarize the clinical impact of PHT on the course of liver disease, discuss the underlying pathophysiological link of PHT to gut-liver axis signaling, and provide insight into molecular mechanisms that may represent novel therapeutic targets.


Assuntos
Disbiose/imunologia , Hipertensão Portal/etiologia , Mucosa Intestinal/metabolismo , Cirrose Hepática/complicações , Fígado/patologia , Animais , Translocação Bacteriana/imunologia , Modelos Animais de Doenças , Progressão da Doença , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Hipertensão Portal/metabolismo , Hipertensão Portal/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/microbiologia , Padrões Moleculares Associados a Patógenos/imunologia , Padrões Moleculares Associados a Patógenos/metabolismo , Permeabilidade
5.
J Agric Food Chem ; 67(42): 11665-11674, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31588753

RESUMO

A long-term high-fat diet (HFD) can cause a range of health problems. Gut microbiota plays a decisive role in the development of HFD-associated inflammation, involved in function of T cells. This study was designed to probe the regulative effects of dietary stachyose, a functional oligosaccharide, on HFD-induced weight gain, inflammation, gut microbiota dysbiosis, and T cell abnormality in C57Bl/6 mice. Mice were divided into three groups which received normal chow, HFD and HFD plus stachyose (400 mg/kg), respectively. Results showed that administration of stachyose diminished the HFD-induced upregulation of serum TNF-α level and elevation of peripheral blood leukocyte populations to alleviate the HFD-caused colonic and hepatic inflammation in mice. Analysis of gut microbiota revealed that stachyose improved the intestinal homeostasis of HFD-fed mice by improving the bacterial diversity with the increases in the relative abundances of the Prevotellaceae_NK3B31_group, Parasutterella, Christensenellaceae_R-7_group, and Anaerovorax, as well as the fecal level of butanoic acid, while decreasing the ratio of Firmicutes-to-Bacteroidetes and the abundances of the Lachnospiraceae_NK4A136_group, Desulfovibrio, Anaerotruncus, Mucispirillum, Roseburia, and Odoribacter. Flow cytometric analysis showed that stachyose antagonized the HFD-induced decrease of peripheral CD4+ T cell population in mice. Conclusively, these findings suggest that long-term consumption of stachyose can ameliorate the HFD-associated colonic and hepatic inflammation and its complications by modulating gut microbiota.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Colo/imunologia , Disbiose/dietoterapia , Microbioma Gastrointestinal , Fígado/imunologia , Oligossacarídeos/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Colo/microbiologia , Dieta Hiperlipídica/efeitos adversos , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Food Funct ; 10(10): 6331-6341, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524900

RESUMO

Increased consumption of fruits may decrease the risk of chronic inflammatory diseases including inflammatory bowel disease (IBD). Gut microbiota dysbiosis plays an important etiological role in IBD. However, the mechanisms of action underlying the anti-inflammatory effects of dietary cranberry (Vaccinium macrocarpon) in the colon and its role on gut microbiota were unclear. In this study, we determined the anti-inflammatory efficacy of whole cranberry in a mouse model of dextran sodium sulfate (DSS)-induced colitis, as well as its effects on the structure of gut microbiota. The results showed that dietary cranberry significantly decreased the severity of colitis in DSS-treated mice, evidenced by increased colon length, and decreased disease activity and histologic score of colitis in DSS-treated mice compared to the positive control group (p < 0.05). Moreover, the colonic levels of pro-inflammatory cytokine (IL-1ß, IL-6 and TNF-α) were significantly reduced by cranberry supplementation (p < 0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels revealed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice. α diversity was significantly decreased in the DSS group, compared to the healthy control group. But, cranberry treatment significantly improved DSS-induced decline in α-diversity. Moreover, cranberry treatment partially reversed the change of gut microbiota in colitic mice by increasing the abundance of potential beneficial bacteria, for example, Lactobacillus and Bifidobacterium, and decreasing the abundance of potential harmful bacteria, such as Sutterella and Bilophila. Overall, our results for the first time demonstrated that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of colitis in DSS-treated mice.


Assuntos
Colite/dietoterapia , Disbiose/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Vaccinium macrocarpon/metabolismo , Animais , Colite/imunologia , Colite/microbiologia , Colo/imunologia , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Disbiose/induzido quimicamente , Disbiose/genética , Disbiose/imunologia , Frutas/química , Frutas/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Sulfatos/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vaccinium macrocarpon/química
7.
Int J Mol Sci ; 20(18)2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540133

RESUMO

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.


Assuntos
Alcoolismo/microbiologia , Microbioma Gastrointestinal/fisiologia , Hepatopatias Alcoólicas/microbiologia , Alcoolismo/genética , Alcoolismo/imunologia , Alcoolismo/fisiopatologia , Animais , Antibacterianos/efeitos adversos , Ácidos e Sais Biliares/metabolismo , Dieta , Suplementos Nutricionais/microbiologia , Disbiose/imunologia , Disbiose/metabolismo , Transplante de Microbiota Fecal , Hepatócitos/metabolismo , Humanos , Intestinos/microbiologia , Fígado/metabolismo , Fígado/fisiopatologia , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/fisiopatologia
8.
Nutrients ; 11(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540270

RESUMO

The human intestine contains an intricate ecological community of dwelling bacteria, referred as gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, antibiotics, as well as environmental factors, particularly diet, thus causing a disruption of microbiota equilibrium (dysbiosis). Growing evidences support the involvement of GM dysbiosis in gastrointestinal (GI) and extra-intestinal cardiometabolic diseases, namely obesity and diabetes. This review firstly overviews the role of GM in health and disease, then critically reviews the evidences regarding the influence of dietary polyphenols in GM based on preclinical and clinical data, ending with strategies under development to improve efficiency of delivery. Although the precise mechanisms deserve further clarification, preclinical and clinical data suggest that dietary polyphenols present prebiotic properties and exert antimicrobial activities against pathogenic GM, having benefits in distinct disorders. Specifically, dietary polyphenols have been shown ability to modulate GM composition and function, interfering with bacterial quorum sensing, membrane permeability, as well as sensitizing bacteria to xenobiotics. In addition, can impact on gut metabolism and immunity and exert anti-inflammatory properties. In order to overcome the low bioavailability, several different approaches have been developed, aiming to improve solubility and transport of dietary polyphenols throughout the GI tract and deliver in the targeted intestinal regions. Although more research is still needed, particularly translational and clinical studies, the biotechnological progresses achieved during the last years open up good perspectives to, in a near future, be able to improve the use of dietary polyphenols modulating GM in a broad range of disorders characterized by a dysbiotic phenotype.


Assuntos
Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Animais , Disponibilidade Biológica , Diabetes Mellitus/microbiologia , Disbiose/complicações , Disbiose/imunologia , Disbiose/microbiologia , Gastroenteropatias/etiologia , Gastroenteropatias/microbiologia , Humanos , Imunidade , Inflamação , Obesidade/complicações , Obesidade/microbiologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem
9.
Int J Mol Sci ; 20(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540277

RESUMO

The association between rheumatoid arthritis (RA) and periodontal disease (PD) has been the focus of numerous investigations driven by their common pathological features. RA is an autoimmune disease characterized by chronic inflammation, the production of anti-citrullinated proteins antibodies (ACPA) leading to synovial joint inflammation and destruction. PD is a chronic inflammatory condition associated with a dysbiotic microbial biofilm affecting the supporting tissues around the teeth leading to the destruction of mineralized and non-mineralized connective tissues. Chronic inflammation associated with both RA and PD is similar in the predominant adaptive immune phenotype, in the imbalance between pro- and anti-inflammatory cytokines and in the role of smoking and genetic background as risk factors. Structural damage that occurs in consequence of chronic inflammation is the ultimate cause of loss of function and disability observed with the progression of RA and PD. Interestingly, the periodontal pathogen Porphyromonas gingivalis has been implicated in the generation of ACPA in RA patients, suggesting a direct biological intersection between PD and RA. However, more studies are warranted to confirm this link, elucidate potential mechanisms involved, and ascertain temporal associations between RA and PD. This review is mainly focused on recent clinical and translational research intends to discuss and provide an overview of the relationship between RA and PD, exploring the similarities in the immune-pathological aspects and the possible mechanisms linking the development and progression of both diseases. In addition, the current available treatments targeting both RA and PD were revised.


Assuntos
Anticorpos Anti-Proteína Citrulinada/metabolismo , Artrite Reumatoide/imunologia , Periodontite/microbiologia , Citocinas/metabolismo , Progressão da Doença , Disbiose/imunologia , Disbiose/microbiologia , Regulação da Expressão Gênica , Humanos , Periodontite/imunologia , Porphyromonas gingivalis/imunologia
10.
Chin J Nat Med ; 17(8): 600-607, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472897

RESUMO

To recognize the potential medicinal value of the Dendrobium sonia, polysaccharide (DSP) was extracted, purified, and investigated for its immunomodulatory activity. In vitro, DSP was shown to enhance the viability (MTT assay) and phagocytosis of macrophages. In cyclophosphamide-induced immunosuppressed mice, DSP increased serum levels of TNF-α, IL-6 and IFN-γ (enzyme-linked immunosorbent assay, ELISA), and ameliorated the imbalance of the community of gut microbiota as detected by 16S ribosomal RNA gene sequencing. These results suggest that DSP might be beneficial for patients under immunosuppressed conditions.


Assuntos
Dendrobium/química , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hospedeiro Imunocomprometido , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Animais , Ciclofosfamida/toxicidade , Citocinas/sangue , Disbiose/induzido quimicamente , Disbiose/imunologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Monossacarídeos/química , Fagocitose/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Células RAW 264.7
11.
Psychiatr Danub ; 31(Suppl 3): 381-385, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488756

RESUMO

BACKGROUND: Psychiatric disorders may be correlated with a low-grade systemic inflammation but the origin of this inflammatory response remains unclear and both genetics and environmental factors seems to be concerned. Recent researches observed that gut microbiota seems to have an impact on the brain and immune processes. METHOD: We review recent literature to a better understanding of how microbiota interacts with brain, immunity and psychiatric disorders. We search on Pubmed, PsycINFO, PsycARTICLES and Sciencedirect articles with the keywords "gastrointestinal microbiota" and "mental disorders" or "psychological stress". RESULTS: We showed links between gut microbiota and brain-gut axis regulation, immune and endocrine system activity, neurophysiological changes, behavior variations and neuropsychiatric disorders. Communications between brain and gut are bidirectional via neural, endocrine and immune pathway. Microbiota dysbiosis and increase gut permeability with subsequent immune challenges seems to be the source of the chronic mild inflammation associated with neuropsychiatric disorders. Repeated immune or stress events early in life may lead to neurodevelopmental disorders or sickness behavior later in life. CONCLUSIONS: Psychological stress impact gut microbiota with subsequent immune activation leading to neurodevelopmental disorders or sickness behavior and altering neurophysiology and reactivity to stress or lifestyle.


Assuntos
Encéfalo/imunologia , Encéfalo/fisiopatologia , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Inflamação/imunologia , Inflamação/psicologia , Transtornos Mentais/imunologia , Transtornos Mentais/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/psicologia , Sistema Endócrino/imunologia , Sistema Endócrino/metabolismo , Sistema Endócrino/microbiologia , Humanos , Inflamação/microbiologia , Neuropsiquiatria , Estresse Psicológico/imunologia , Estresse Psicológico/microbiologia
12.
Food Funct ; 10(9): 5952-5968, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475718

RESUMO

Methionine-restricted diets (MRD) have been shown to prevent high fat diet (HFD) induced complications including fat accumulation, insulin sensitivity decrease, oxidative stress and inflammation increase. We hypothesized that intestinal microbiota changes may mediate these effects, and this study aims to prove this hypothesis. Mice were fed a normal diet (ND, 0.86% methionine + 4% fat), a HF diet (HFD, 0.86% methionine + 20% fat), or a MRD (0.17% methionine + 20% fat) and euthanized at week 22. Our results showed that the HFD induced fat accumulation and gut microbiota dysbiosis; reduced short-chain fatty acid (SCFA) production; and increased intestinal permeability, inflammatory response, and oxidative stress. The MRD decreased the body weight, body fat rate, and blood glucose and plasma lipid levels; increased the abundance of putative SCFA-producing bacteria Bifidobacterium, Lactobacillus, Bacteroides, Roseburia, Coprococcus, and Ruminococcus and inflammation-inhibiting bacteria Oscillospira and Corynebacterium; and decreased the abundance of inflammation-producing bacteria Desulfovibrio in colonic contents. Moreover, the MRD improved intestinal barrier function, inflammatory response, and oxidative stress, and altered the metabolite levels of colonic contents (such as increasing SCFA and bile acid concentrations); the latter may have contributed to the prevention of HFD-induced obesity. In conclusion, the MRD can improve gut health by regulating the intestinal microbiota and its metabolite profiles in the HFD mice. Reducing methionine intake by simple dietary adjustment may be an effective method to improve intestinal health in animals and humans.


Assuntos
Disbiose/dietoterapia , Disbiose/imunologia , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Metionina/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Disbiose/metabolismo , Disbiose/microbiologia , Ácidos Graxos Voláteis/metabolismo , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Masculino , Metionina/análise , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade
13.
Gastroenterology ; 157(6): 1530-1543.e4, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31445037

RESUMO

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.


Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Proteínas de Bactérias/imunologia , Toxina da Cólera/imunologia , Diarreia/diagnóstico , Diarreia/imunologia , Diarreia/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Feminino , Vida Livre de Germes , Humanos , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Pneumonia/diagnóstico , Pneumonia/imunologia , Pneumonia/microbiologia , Índice de Gravidade de Doença
14.
Immunity ; 51(2): 214-224, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31433969

RESUMO

In ecological terms, the microbiome is defined as the microbiota and its environment, a definition that encompasses the human host. The size, species composition, and biogeography of microbial communities is shaped by host interactions, and, in turn, the microbiota influences many aspects of human health. Here we discuss the concept of microbiota-nourishing immunity, a host-microbe chimera composed of the microbiota and host factors that shape the microbial ecosystem, which functions in conferring colonization resistance against pathogens. We propose that dysbiosis is a biomarker of a weakening in microbiota-nourishing immunity and that homeostasis can be defined as a state of immune competence. Microbiota-nourishing immunity thus provides a conceptual framework to further examine the mechanisms that preserve a healthy microbiome and the drivers and consequences of dysbiosis.


Assuntos
Disbiose/imunologia , Interações Hospedeiro-Patógeno , Microbiota/imunologia , Animais , Autoantígenos/imunologia , Homeostase , Humanos , Imunidade , Imunocompetência , Tolerância a Antígenos Próprios
15.
Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31308086

RESUMO

As important players in the host defense system, commensal microbes and the microbiota influence multiple aspects of host physiology. Bordetella pertussis infection is highly contagious among humans. However, the roles of the microbiota in B. pertussis pathogenesis are poorly understood. Here, we show that antibiotic-mediated depletion of the microbiota results in increased susceptibility to B. pertussis infection during the early stage. The increased susceptibility was associated with a marked impairment of the systemic IgG, IgG2a, and IgG1 antibody responses to B. pertussis infection after antibiotic treatment. Furthermore, the microbiota impacted the short-lived plasma cell responses as well as the recall responses of memory B cells to B. pertussis infection. Finally, we found that the dysbiosis caused by antibiotic treatment affects CD4+ T cell generation and PD-1 expression on CD4+ T cells and thereby perturbs plasma cell differentiation. Our results have revealed the importance of commensal microbes in modulating host immune responses to B. pertussis infection and support the possibility of controlling the severity of B. pertussis infection in humans by manipulating the microbiota.


Assuntos
Bordetella pertussis/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Humoral , Simbiose/imunologia , Coqueluche/imunologia , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/classificação , Bacteroidetes/classificação , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/imunologia , Bordetella pertussis/crescimento & desenvolvimento , Bordetella pertussis/patogenicidade , Disbiose/microbiologia , Disbiose/fisiopatologia , Feminino , Firmicutes/classificação , Firmicutes/efeitos dos fármacos , Firmicutes/crescimento & desenvolvimento , Firmicutes/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata , Imunoglobulina G/biossíntese , Imunoglobulina G/classificação , Metronidazol/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Neomicina/farmacologia , Proteobactérias/classificação , Proteobactérias/efeitos dos fármacos , Proteobactérias/crescimento & desenvolvimento , Proteobactérias/imunologia , Simbiose/efeitos dos fármacos , Vancomicina/farmacologia , Coqueluche/microbiologia , Coqueluche/fisiopatologia
16.
Arthritis Rheumatol ; 71(11): 1849-1857, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31216122

RESUMO

OBJECTIVE: To define inflammation-related host-microbe interactions in experimental spondyloarthritis (SpA) using novel inter-omic approaches. METHODS: The relative frequency of gut microbes was determined by 16S ribosomal RNA (rRNA) gene sequencing, and gene expression using RNA-Seq of host tissue. HLA-B27/human ß2 -microglobulin-transgenic (HLA-B27-transgenic) and wild-type rats from dark agouti, Lewis, and Fischer backgrounds were used. Inter-omic analyses using Cytoscape were employed to identify relevant relationships. PICRUSt was used to predict microbial functions based on known metagenomic profiles. RESULTS: Inter-omic analysis revealed several gut microbes that were strongly associated with dysregulated cytokines driving inflammatory response pathways, such as interleukin-17 (IL-17), IL-23, IL-17, IL-1, interferon-γ (IFNγ), and tumor necrosis factor (TNF). Many microbes were uniquely associated with inflammation in Lewis or Fischer rats, and one was relevant on both backgrounds. Several microbes that were strongly correlated with immune dysregulation were not differentially abundant in HLA-B27-transgenic compared to wild-type controls. A multi-omic network analysis revealed non-overlapping clusters of microbes in Lewis and Fischer rats that were strongly linked to overlapping dysregulated immune/inflammatory genes. Prevotella, Clostridiales, and Blautia were important in Lewis rats, while Akkermansia muciniphila and members of the Lachnospiraceae family dominated in Fischer rats. Inflammation-associated metabolic pathway perturbation (e.g., butanoate, propanoate, lipopolysaccharide, and steroid biosynthesis) was also predicted from both backgrounds. CONCLUSION: Inter-omic and network analysis of gut microbes and the host immune response in experimental SpA provides an unprecedented view of organisms strongly linked to dysregulated IL-23, IL-17, IL-1, IFNγ, and TNF. Functional similarities between these organisms may explain why animals of different genetic backgrounds exhibit common patterns of immune dysregulation, possibly through perturbation of similar metabolic pathways. These results highlight the power of linking analyses of gut microbiota with the host immune response to gain insights into the role of dysbiotic microbes in SpA beyond taxonomic profiling.


Assuntos
Artrite Experimental/imunologia , Artrite Experimental/microbiologia , Citocinas/imunologia , Microbioma Gastrointestinal/genética , Antígeno HLA-B27/imunologia , Espondiloartropatias/imunologia , Espondiloartropatias/microbiologia , Animais , Clostridiales , Disbiose/imunologia , Disbiose/microbiologia , Feminino , Perfilação da Expressão Gênica , Antígeno HLA-B27/genética , Humanos , Interferon gama/imunologia , Interleucina-1/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Masculino , Prevotella , RNA Ribossômico 16S/genética , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Ratos Transgênicos , Fator de Necrose Tumoral alfa/imunologia , Verrucomicrobia
17.
Nat Med ; 25(7): 1164-1174, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235962

RESUMO

The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated. Therapy with Clostridiales species impacted by dysbiosis, either as a consortium or as monotherapy with Subdoligranulum variabile, suppressed FA in mice as did a separate immunomodulatory Bacteroidales consortium. Bacteriotherapy induced expression by regulatory T (Treg) cells of the transcription factor ROR-γt in a MyD88-dependent manner, which was deficient in FA infants and mice and ineffectively induced by their microbiota. Deletion of Myd88 or Rorc in Treg cells abrogated protection by bacteriotherapy. Thus, commensals activate a MyD88/ROR-γt pathway in nascent Treg cells to protect against FA, while dysbiosis impairs this regulatory response to promote disease.


Assuntos
Hipersensibilidade Alimentar/terapia , Microbioma Gastrointestinal/imunologia , Fator 88 de Diferenciação Mieloide/fisiologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/fisiologia , Linfócitos T Reguladores/fisiologia , Animais , Bacteroides , Clostridiales , Disbiose/imunologia , Fezes/microbiologia , Hipersensibilidade Alimentar/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Transdução de Sinais
18.
Poult Sci ; 98(11): 5432-5445, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247643

RESUMO

The intent of this study was to investigate the effects of cold stress on oxidative indexes, inflammatory factors, and microbiota in the quail cecum. A total of 192 male quails (15-day-old) were randomly divided into 12 groups (16 in each group) and were exposed to acute (up to 12 h) and chronic (up to 20 D) cold stress at 12 ± 1°C. After cold stress treatment, we examined morphological damage, oxidative stress indexes, inflammatory factors, and intestinal microbiota. Results of morphological examination showed that both acute and chronic cold stress can lead to cecal tissue injury. In addition, both acute and chronic cold stress, especially chronic cold stress can influence the activity of oxidative stress mediators. Glutathione (GSH) and glutathione peroxidase (GSH-Px) activities decreased significantly (p < 0.05), while the nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity increased significantly (p < 0.05). Moreover, mRNA levels of inflammatory factors cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), and heat shock protein 70 (Hsp70) were higher in both acute and chronic cold stress groups when compared with the control group (p < 0.05). Furthermore, the intestinal microbiota was changed in both the acute and chronic cold stress groups. These results suggested that cold stress caused oxidative stress and inflammatory injury in cecal tissues, influenced cecal microbiota, and increased expression of Hsp70, which may contribute in protecting the cecum against cold stress in quails.


Assuntos
Ceco/fisiologia , Temperatura Baixa/efeitos adversos , Proteínas de Choque Térmico HSP70/genética , Inflamação/veterinária , Estresse Oxidativo , Codorniz/fisiologia , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Ceco/imunologia , Ceco/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/veterinária , Microbioma Gastrointestinal , Proteínas de Choque Térmico HSP70/metabolismo , Inflamação/imunologia , Inflamação/microbiologia , Codorniz/genética , Codorniz/imunologia
19.
Cell Mol Life Sci ; 76(20): 3917-3937, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250035

RESUMO

The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.


Assuntos
Imunidade Adaptativa , Disbiose/metabolismo , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Mucosa Intestinal/metabolismo , Metaboloma/imunologia , Aminoácidos/imunologia , Aminoácidos/metabolismo , Animais , Ácidos e Sais Biliares/imunologia , Ácidos e Sais Biliares/metabolismo , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/terapia , Ácidos Graxos/imunologia , Ácidos Graxos/metabolismo , Transplante de Microbiota Fecal , Vida Livre de Germes/imunologia , Homeostase/imunologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/microbiologia , Células Mieloides/imunologia , Células Mieloides/metabolismo , Células Mieloides/microbiologia , Simbiose/imunologia
20.
J Drugs Dermatol ; 18(6): 581, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251552

RESUMO

The skin is one of the largest immunologic organs in the body and a continuous target for allergic and immunologic responses. Impairment of the skin barrier increases the likelihood of external antigens and pathogens entering and creating inflammation, which can potentially lead to skin infections, allergies, and chronic inflammatory diseases such as atopic and contact dermatitis. Functionally, the skin barrier can be divided into four different levels. From outermost to innermost, these highly interdependent levels are the microbiome, chemical, physical, and immune levels. The objective of this review is to provide an update on current knowledge about the relationship between skin barrier function and how dysfunction at each level of the skin barrier can lead to allergic sensitization, contact dermatitis, and the atopic march, and examine how to best repair and maintain this barrier through the use of moisturizers. J Drugs Dermatol. 2019;18(6):581-586.


Assuntos
Dermatite Alérgica de Contato/prevenção & controle , Dermatite Atópica/prevenção & controle , Emolientes/administração & dosagem , Dermatopatias Infecciosas/prevenção & controle , Pele/metabolismo , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/microbiologia , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/prevenção & controle , Humanos , Microbiota/imunologia , Permeabilidade/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/microbiologia , Creme para a Pele/administração & dosagem , Dermatopatias Infecciosas/imunologia , Dermatopatias Infecciosas/microbiologia
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