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1.
Scand J Immunol ; 90(3): e12799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211854

RESUMO

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1ß, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1ß, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.


Assuntos
Doenças Autoimunes/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Pênfigo/imunologia , Plasma/imunologia , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/microbiologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Pênfigo/microbiologia , Plasma/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Células Th2/imunologia , Células Th2/microbiologia
2.
Autoimmun Rev ; 18(5): 455-475, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844549

RESUMO

The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.


Assuntos
Doenças Autoimunes/metabolismo , Doenças Autoimunes/microbiologia , Doenças Autoimunes/terapia , Interações entre Hospedeiro e Microrganismos/fisiologia , Doenças Autoimunes/imunologia , Autoimunidade/fisiologia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Humanos , Redes e Vias Metabólicas/imunologia , Prebióticos/microbiologia , Probióticos/metabolismo , Probióticos/uso terapêutico
3.
World J Gastroenterol ; 25(9): 1050-1066, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30862994

RESUMO

BACKGROUND: The bacteria Campylobacter jejuni (C. jejuni) is commonly associated with Guillane-Barré syndrome (GBS) and irritable bowel syndrome (IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be cross-reactive with some human tissues and food antigens, potentially leading to autoimmune responses. AIM: To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin (Cdt) antibodies with tissue and food antigens to examine their role in autoimmunities. METHODS: Using enzyme-linked immunosorbent assay (ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin (HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive controls. RESULTS: At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, ß-amyloid and presenilin. This immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, including neuronal antigens. The reaction of C. jejuni Cdt antibody with an additional 23 tissue antigens was insignificant. Regarding the reaction of C. jejuni Cdt antibody with different food antigens, 160 out of 180 foods showed insignificant reactions, while 20 foods showed reactions ranging from low to high. CONCLUSION: Our findings indicate that C. jejuni and its Cdt may play a role in inflammation and autoimmunities beyond the gut.


Assuntos
Anticorpos Antibacterianos/imunologia , Doenças Autoimunes/imunologia , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Doenças Autoimunes/microbiologia , Autoimunidade , Toxinas Bacterianas/imunologia , Toxina da Cólera/imunologia , Reações Cruzadas/imunologia , Proteínas na Dieta/imunologia , Hormônio do Crescimento Humano/imunologia , Humanos , Fator Intrínseco/imunologia
4.
Immunology ; 156(4): 297-298, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30873603

RESUMO

Th17-derived IL-17 might be considered the archetypal pro-inflammatory cytokine of adaptive immunity, to be targeted by new therapeutics for alleviation of autoimmune and inflammatory disease. However, the IL-17 family of cytokines is produced by diverse innate and adaptive cells, including Th17, Tc17, ILC3, NK cells and γδ T-cells. These responses are appreciated to underpin diverse aspects of protective, physiological immunity, from dialogue with the gut microbiota to bacterial and fungal immunity in the lung.


Assuntos
Células Th17/imunologia , Imunidade Adaptativa/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Bactérias/imunologia , Fungos/imunologia , Microbioma Gastrointestinal/imunologia , Humanos
5.
Int J Mol Sci ; 20(2)2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30642013

RESUMO

Autoimmune disorders derive from genetic, stochastic, and environmental factors that all together interact in genetically predisposed individuals. The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models and humans. Several physiological mechanisms, including the establishment of immune homeostasis, are influenced by commensal microbiota in the gut. An altered microbiota composition produces effects in the gut immune system, including defective tolerance to food antigens, intestinal inflammation, and enhanced gut permeability. In particular, early findings reported differences in the intestinal microbiome of subjects affected by several autoimmune conditions, including prediabetes or overt disease compared to healthy individuals. The present review focuses on microbiota-host homeostasis, its alterations, factors that influence its composition, and putative involvement in the development of autoimmune disorders. In the light of the existing literature, future studies are necessary to clarify the role played by microbiota modifications in the processes that cause enhanced gut permeability and molecular mechanisms responsible for autoimmunity onset.


Assuntos
Doenças Autoimunes/microbiologia , Disbiose/imunologia , Trato Gastrointestinal/microbiologia , Animais , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Disbiose/complicações , Trato Gastrointestinal/imunologia , Humanos , Redes e Vias Metabólicas , Microbiota
6.
Invest Ophthalmol Vis Sci ; 60(1): 420-429, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30695094

RESUMO

Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis. Methods: Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice with coadministration of interphotoreceptor retinoid-binding protein peptide (IRBP) and killed mycobacterial antigen (MTB) as an adjuvant. Using 16S rRNA gene sequencing, we looked at intestinal microbial differences during the course of uveitis, as well as intestinal morphologic changes, changes in intestinal permeability by FITC-dextran leakage, antimicrobial peptide expression in the gastrointstinal tract, and T lymphocyte prevalence before and at peak intraocular inflammation. Results: We demonstrate that increased intestinal permeability and antimicrobial peptide expression in the intestinal tract coincide in timing with increased effector T cells in the mesenteric lymph nodes, during the early stages of uveitis, before peak inflammation. Morphologic changes in the intestine were most prominent during this phase, but also occurred with adjuvant MTB alone, whereas increased intestinal permeability was found only in IRBP-immunized mice that develop uveitis. We also demonstrate that the intestinal microbiota were altered during the course of uveitis, and that some of these changes are specific to uveitic animals, whereas others are influenced by adjuvant MTB alone. Intestinal permeability peaked at 2 weeks, coincident with an increase in intestinal bacterial strain differences, peak lipocalin production, and peak uveitis. Conclusions: An intestinal dysbiosis accompanies a disruption in intestinal homeostasis in autoimmune uveitis, although adjuvant MTB alone promotes intestinal disruption as well. This may indicate a novel axis for future therapeutic targeting experimentally or clinically.


Assuntos
Doenças Autoimunes/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Homeostase/fisiologia , Intestinos/fisiologia , Uveíte/microbiologia , Animais , Antígenos de Bactérias/imunologia , Doenças Autoimunes/imunologia , Ensaio de Imunoadsorção Enzimática , Proteínas do Olho , Citometria de Fluxo , Lipocalinas/metabolismo , Camundongos , Camundongos Mutantes , Modelos Animais , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , RNA Ribossômico 16S/genética , Proteínas de Ligação ao Retinol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subpopulações de Linfócitos T/imunologia , Uveíte/imunologia , Proteína da Zônula de Oclusão-1/metabolismo
8.
Ann Dermatol Venereol ; 145 Suppl 7: VIIS17-VIIS23, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30583753

RESUMO

A traditional lecture given during the annual meeting of the French Society of Dermatology in Paris summarizes the highlights of the scientific literature over the past year. In the current article the selection of the 2017-2018 period retains the following areas of interest: role of microbiome in the response to anti-PD-1 and in autoimmunity, PI3Kδ inhibitors in autoimmune bullous diseases, diagnostic and therapeutic applications of CRISPR/Cas, arrival of CAR-T cells therapy into clinical practice, gene therapy successes, use of targeted therapies in genodermatoses and integration of genetics in primary care. © 2018 Elsevier Masson SAS. All rights reserved.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Microbioma Gastrointestinal/imunologia , Imunoterapia Adotiva , Dermatopatias/terapia , Doenças Autoimunes/microbiologia , Carcinoma Basocelular/genética , DNA Tumoral Circulante/genética , Dermatologia/tendências , Epidermólise Bolhosa/imunologia , Terapia Genética , Humanos , Hipotricose/genética , Imunoterapia , Proteínas dos Microfilamentos/genética , Mutação , Proteínas de Neoplasias/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Dermatopatias/genética , Neoplasias Cutâneas/genética
9.
Front Immunol ; 9: 2617, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532751

RESUMO

The rising global incidence of autoimmune and inflammatory conditions can be attributed to changes in the large portion of the immune system that belongs to our gastrointestinal tract (GI). The intestinal immune system serves as a gatekeeper to prevent pathogenic invasions and to preserve a healthier gut microbiota. The gut microbiota has been increasingly studied as a fundamental contributor to the state of health and disease. From food fermentation, the gut microbiota releases metabolites or short chain fatty acids (SCFAs), which have anti-inflammatory properties and preserve gut homeostasis. Immune responses against food and microbial antigens can cause inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease. As such, many autoimmune and inflammatory diseases also have a "gut origin". A large body of evidence in recent years by ourselves and others has uncovered the link between the immune system and the SCFAs in specific diseases such as autoimmune type 1 diabetes (T1D), obesity and type 2 diabetes (T2D), cardiovascular disease, infections, allergies, asthma, and IBD. Thus, the power of these three gut dynamic components-the mucosal immunity, the microbiota, and diet-can be harnessed in tandem for the prevention and treatment of many inflammatory and infectious diseases.


Assuntos
Doenças Autoimunes/imunologia , Microbioma Gastrointestinal , Hipersensibilidade/imunologia , Imunidade nas Mucosas , Infecção/imunologia , Inflamação/imunologia , Mucosa Intestinal/imunologia , Animais , Doenças Autoimunes/microbiologia , Dieta , Disbiose , Homeostase , Humanos , Hipersensibilidade/microbiologia , Infecção/microbiologia , Inflamação/microbiologia , Mucosa Intestinal/microbiologia
10.
Nutrients ; 10(8)2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30081517

RESUMO

A leaky gut has been observed in a number of autoimmune diseases including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. Previous studies from our laboratory have shown that lupus mice also bear a leaky gut and that the intestinal barrier function can be enhanced by gut colonization of probiotics such as Lactobacillus spp. Retinoic acid (RA) can increase the relative abundance of Lactobacillus spp. in the gut. Interestingly, RA has also been shown to strengthen the barrier function of epithelial cells in vitro and in the absence of probiotic bacteria. These reports bring up an interesting question of whether RA exerts protective effects on the intestinal barrier directly or through regulating the microbiota colonization. In this review, we will discuss the roles of RA in immunomodulation, recent literature on the involvement of a leaky gut in different autoimmune diseases, and how RA shapes the outcomes of these diseases.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Autoimunidade/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Intestinos/efeitos dos fármacos , Tretinoína/uso terapêutico , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Doenças Autoimunes/fisiopatologia , Bactérias/crescimento & desenvolvimento , Bactérias/imunologia , Interações Hospedeiro-Patógeno , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Intestinos/fisiopatologia , Permeabilidade , Resultado do Tratamento
11.
Science ; 359(6380): 1156-1161, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29590047

RESUMO

Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.


Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/microbiologia , Autoimunidade/genética , Translocação Bacteriana , Enterococcus/fisiologia , Microbioma Gastrointestinal/fisiologia , Predisposição Genética para Doença , Animais , Antibacterianos/farmacologia , Autoanticorpos/imunologia , Autoimunidade/imunologia , Vacinas Bacterianas/imunologia , DNA Bacteriano/análise , Enterococcus/efeitos dos fármacos , Enterococcus/imunologia , Hepatócitos/microbiologia , Humanos , Fígado/microbiologia , Camundongos , Linfócitos T/imunologia
12.
Nat Commun ; 9(1): 1014, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523850

RESUMO

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-γ (IFNγ) production in stimulated natural killer cells, and decreased circulating IFNγ concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFNγ-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.


Assuntos
Doenças Autoimunes/genética , Bacteriemia/epidemiologia , Predisposição Genética para Doença , Fator de Transcrição STAT4/genética , Infecções por Salmonella/epidemiologia , Salmonella/patogenicidade , Adolescente , Alelos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Bacteriemia/genética , Bacteriemia/imunologia , Bacteriemia/microbiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imunidade Celular/genética , Lactente , Recém-Nascido , Interferon gama/sangue , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-12/imunologia , Interleucina-12/metabolismo , Quênia/epidemiologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Malaui/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Fatores de Risco , Salmonella/isolamento & purificação , Infecções por Salmonella/genética , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia
13.
Eur J Paediatr Neurol ; 22(2): 316-320, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29398245

RESUMO

The terms Pediatric Autoimmune Neuropsychiatric disorders associated with streptococcal infections (PANDAS), Pediatric acute-onset neuropsychiatric Syndrome (PANS), and Childhood Acute Neuropsychiatric Symptoms (CANS) have been used to describe certain acute onset neuropsychiatric pediatric disorders. This clinical characteristic was unusually abrupt onset of obsessive compulsive symptoms and/or severe eating restrictions and concomitant cognitive, behavioral or neurological symptoms. Because the CANS/PANS criteria define a broad spectrum of neuropsychiatric conditions, the syndrome is presumed to result from a variety of disease mechanisms and to have multiple etiologies, ranging from postinfectious autoimmune and neuroinflammatory disorders to toxic, endocrine or metabolic disorders. We suggest a diagnostic flow-chart in case of acute onset neuropsychiatric syndrome to better define diagnostic criteria, identify possible subtypes and delineate treatment.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/psicologia , Infecção/psicologia , Transtornos Mentais/imunologia , Transtornos Mentais/microbiologia , Doenças Autoimunes/microbiologia , Criança , Feminino , Humanos , Infecção/complicações , Síndrome
14.
Tohoku J Exp Med ; 244(2): 113-117, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29434076

RESUMO

Host-derived factors alter gut microenvironment, and changes in gut microbiota also affect biological functions of host. Alterations of gut microbiota have been reported in a wide variety of diseases, but the whole picture of alterations in pancreatic diseases remains to be clarified. In particular, the gut microbiota may be affected by malnutrition or impaired exocrine pancreas function that is associated with pancreatic diseases. We here conducted comprehensive analysis of gut microbiota in patients with type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of the systemic IgG4-related disease, and chronic pancreatitis (CP). The two diseases were selected, because altered immune reactions in AIP and/or long-standing malnutrition in CP may influence the gut microbiota. Fecal samples were obtained from 12 patients with AIP before the steroid therapy and 8 patients with CP. Metagenome DNA was extracted, and microbiota was analyzed by next generation sequencing. Gut microbiota profiles were different between patients with AIP and those with CP; namely, the proportions of Bacteroides, Streptococcus and Clostridium species were higher in patients with CP. The reasons for the increased proportion of these bacterial species remain unknown, but may reflect malabsorption and/or decreased pancreatic enzymes, both of which are associated with CP. Incidentally, the identified Streptococcus species are oral cavity inhabitants and also known as pathogens for endocarditis. Despite the small sample size, this study has shown the differences in gut microbiota profiles between AIP and CP. Comprehensive analysis of the gut microbiota may be useful for the differential diagnosis of pancreatic diseases.


Assuntos
Doenças Autoimunes/microbiologia , Microbioma Gastrointestinal , Pancreatite Crônica/microbiologia , Idoso , Bactérias/genética , DNA/genética , Fezes/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
15.
BMJ ; 360: j5145, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29311119

RESUMO

The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.


Assuntos
Doenças Autoimunes/microbiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/imunologia , Inflamação/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Membrana Mucosa/microbiologia , Doenças Autoimunes/imunologia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Microbiota , Membrana Mucosa/imunologia , Prebióticos , Probióticos
16.
Wiley Interdiscip Rev Syst Biol Med ; 10(3): e1413, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29316320

RESUMO

Far from being just "bugs in our guts," the microbiota interacts with the body in previously unimagined ways. Research into the genome and the microbiome has revealed that the human body and the microbiota have a long-established but only recently recognized symbiotic relationship; homeostatic balance between them regulates body function. That balance is fragile, easily disturbed, and plays a fundamental role in human health-our very survival depends on the healthy functioning of these microorganisms. Increasing rates of cardiovascular, autoimmune, and inflammatory diseases, as well as epidemics in obesity and diabetes in recent decades are believed to be explained, in part, by unintended effects on the microbiota from vaccinations, poor diets, environmental chemicals, indiscriminate antibiotic use, and "germophobia." Discovery and exploration of the brain-gut-microbiota axis have provided new insights into functional diseases of the gut, autoimmune and stress-related disorders, and the role of probiotics in treating certain affective disorders; it may even explain some aspects of autism. Research into dietary effects on the human gut microbiota led to its classification into three proposed enterotypes, but also revealed the surprising role of blood group antigens in shaping those populations. Blood group antigens have previously been associated with disease risks; their subsequent association with the microbiota may reveal mechanisms that lead to development of nutritional interventions and improved treatment modalities. Further exploration of associations between specific enteric microbes and specific metabolites will foster new dietary interventions, treatment modalities, and genetic therapies, and inevitably, their application in personalized healthcare strategies. This article is categorized under: Laboratory Methods and Technologies > Metabolomics Translational, Genomic, and Systems Medicine > Translational Medicine Physiology > Mammalian Physiology in Health and Disease.


Assuntos
Doenças Autoimunes , Antígenos de Grupos Sanguíneos/metabolismo , Doenças Cardiovasculares , Diabetes Mellitus , Microbioma Gastrointestinal , Obesidade , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/microbiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/microbiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/microbiologia , Humanos , Inflamação/epidemiologia , Inflamação/metabolismo , Inflamação/microbiologia , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/microbiologia
17.
Infect Immun ; 86(3)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29263105

RESUMO

Mycoplasmas are bacterial pathogens of a range of animals, including humans, and are a common cause of respiratory disease. However, the host genetic factors that affect resistance to infection or regulate the resulting pulmonary inflammation are not well defined. We and others have previously demonstrated that nonobese diabetic (NOD) mice can be used to investigate disease loci that affect bacterial infection and autoimmune diabetes. Here we show that NOD mice are more susceptible than C57BL/6 (B6) mice to infection with Mycoplasma pulmonis, a natural model of pulmonary mycoplasmosis. The lungs of infected NOD mice had higher loads of M. pulmonis and more severe inflammatory lesions. Moreover, congenic NOD mice that harbored different B6-derived chromosomal intervals enabled identification and localization of a new mycoplasmosis locus, termed Mpr2, on chromosome 13. These congenic NOD mice demonstrated that the B6 allele for Mpr2 reduced the severity of pulmonary inflammation caused by infection with M. pulmonis and that this was associated with altered cytokine and chemokine concentrations in the infected lungs. Mpr2 also colocalizes to the same genomic interval as Listr2 and Idd14, genetic loci linked to listeriosis resistance and autoimmune diabetes susceptibility, respectively, suggesting that allelic variation within these loci may affect the development of both infectious and autoimmune disease.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Infecções por Mycoplasma/genética , Mycoplasma pulmonis/fisiologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Feminino , Loci Gênicos , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Infecções por Mycoplasma/imunologia , Infecções por Mycoplasma/microbiologia , Mycoplasma pulmonis/genética
18.
PLoS Pathog ; 13(11): e1006653, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095917

RESUMO

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.


Assuntos
Acloridria/microbiologia , Mucosa Gástrica/microbiologia , Microbioma Gastrointestinal , Acloridria/induzido quimicamente , Acloridria/etiologia , Acloridria/imunologia , Adulto , Idoso , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Análise por Conglomerados , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Risco , Neoplasias Gástricas/epidemiologia
19.
Cell Host Microbe ; 22(5): 697-704.e4, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29120746

RESUMO

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity.


Assuntos
Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Autoimunidade , Bactérias/imunologia , Microbioma Gastrointestinal/imunologia , Pulmão/imunologia , Células Th17/imunologia , Animais , Apoptose/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/microbiologia , Autoanticorpos , Bactérias/patogenicidade , Diferenciação Celular/imunologia , Proliferação de Células , Quimiocina CCL20/metabolismo , Modelos Animais de Doenças , Fezes/microbiologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Baço , Simbiose , Células Th17/metabolismo
20.
Wiad Lek ; 70(4): 798-803, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29064808

RESUMO

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.


Assuntos
Artrite Reumatoide/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Microbiota , Doenças Autoimunes/microbiologia , Humanos
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