Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.711
Filtrar
1.
Front Immunol ; 12: 684605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594323

RESUMO

Engineered nanomaterials (ENMs) have been widely exploited in several industrial domains as well as our daily life, raising concern over their potential adverse effects. While in general ENMs do not seem to have detrimental effects on immunity or induce severe inflammation, their indirect effects on immunity are less known. In particular, since the gut microbiota has been tightly associated with human health and immunity, it is possible that ingested ENMs could affect intestinal immunity indirectly by modulating the microbial community composition and functions. In this perspective, we provide a few pieces of evidence and discuss a possible link connecting ENM exposure, gut microbiota and host immune response. Some experimental works suggest that excessive exposure to ENMs could reshape the gut microbiota, thereby modulating the epithelium integrity and the inflammatory state in the intestine. Within such microenvironment, numerous microbiota-derived components, including but not limited to SCFAs and LPS, may serve as important effectors responsible of the ENM effect on intestinal immunity. Therefore, the gut microbiota is implicated as a crucial regulator of the intestinal immunity upon ENM exposure. This calls for including gut microbiota analysis within future work to assess ENM biocompatibility and immunosafety. This also calls for refinement of future studies that should be designed more elaborately and realistically to mimic the human exposure situation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Nanoestruturas/toxicidade , Imunidade Adaptativa , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Imunidade Inata , Imunomodulação
2.
Biomed Pharmacother ; 143: 112228, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649354

RESUMO

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.


Assuntos
Antivirais/imunologia , Antivirais/uso terapêutico , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Informática Médica/métodos , Algoritmos , COVID-19/imunologia , Gerenciamento Clínico , Progressão da Doença , Trato Gastrointestinal/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Índice de Gravidade de Doença
3.
J Clin Invest ; 131(18)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523615

RESUMO

Modern research on gastrointestinal behavior has revealed it to be a highly complex bidirectional process in which the gut sends signals to the brain, via spinal and vagal visceral afferent pathways, and receives sympathetic and parasympathetic inputs. Concomitantly, the enteric nervous system within the bowel, which contains intrinsic primary afferent neurons, interneurons, and motor neurons, also senses the enteric environment and controls the detailed patterns of intestinal motility and secretion. The vast microbiome that is resident within the enteric lumen is yet another contributor, not only to gut behavior, but to the bidirectional signaling process, so that the existence of a microbiota-gut-brain "connectome" has become apparent. The interaction between the microbiota, the bowel, and the brain now appears to be neither a top-down nor a bottom-up process. Instead, it is an ongoing, tripartite conversation, the outline of which is beginning to emerge and is the subject of this Review. We emphasize aspects of the exponentially increasing knowledge of the microbiota-gut-brain "connectome" and focus attention on the roles that serotonin, Toll-like receptors, and macrophages play in signaling as exemplars of potentially generalizable mechanisms.


Assuntos
Encéfalo/fisiologia , Microbioma Gastrointestinal/fisiologia , Animais , Conectoma , Sistema Nervoso Entérico/fisiologia , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/fisiologia , Humanos , Macrófagos/imunologia , Modelos Neurológicos , Vias Neurais/fisiologia
4.
Front Immunol ; 12: 668974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539623

RESUMO

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.


Assuntos
Armadilhas Extracelulares/metabolismo , Imunoglobulina A/sangue , Neutrófilos/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Criança , Pré-Escolar , DNA/sangue , Feminino , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Humanos , /diagnóstico , Rim/imunologia , Rim/metabolismo , Masculino , Ativação de Neutrófilo , Neutrófilos/imunologia , Índice de Gravidade de Doença
5.
Eur J Immunol ; 51(9): 2120-2136, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242413

RESUMO

Fundamental asymmetries between the host and its microbiome in enzymatic activities and nutrient storage capabilities have promoted mutualistic adaptations on both sides. As a result, the enteric immune system has evolved so as not to cause a zero-sum sterilization of non-self, but rather achieve a non-zero-sum self-reinforcing cooperation with its evolutionary partner the microbiome. In this review, we attempt to integrate the accumulated knowledge of immune-microbiome interactions into an evolutionary framework and trace the pattern of positive immune-microbiome feedback loops across epithelial, enteric nervous system, innate, and adaptive immune circuits. Indeed, the immune system requires commensal signals for its development and function, and reciprocally protects the microbiome from nutrient shortage and pathogen outgrowth. In turn, a healthy microbiome is the result of immune system curatorship as well as microbial ecology. The paradigms of host-microbiome asymmetry and the cooperative nature of their interactions identified in the gut are applicable across all tissues influenced by microbial activities. Incorporation of immune system influences into models of microbiome ecology will be a step forward toward defining what constitutes a healthy human microbiome and guide discoveries of novel host-microbiome mutualistic adaptations that may be harnessed for the promotion of human health.


Assuntos
Sistema Nervoso Entérico/fisiologia , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Imunidade Adaptativa/imunologia , Trato Gastrointestinal/inervação , Trato Gastrointestinal/fisiologia , Humanos , Imunidade Inata/imunologia , Simbiose/imunologia
6.
Mol Biol Rep ; 48(7): 5745-5758, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34296352

RESUMO

To date, the latest research results suggest that the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) can enter host cells directly via the gastrointestinal tract by binding to the enterocyte-expressed ACE2 receptor, or indirectly as a result of infection of type II alveolar epithelial cells. At the same time, entry of SARS-CoV-2 through the gastrointestinal tract initiates the activation of innate and adaptive immune responses, the formation of an excessive inflammatory reaction and critical increase in the expression of proinflammatory cytokines, which, subsequently, can presumably increase inflammation and induce intestinal damage in patients suffering from inflammatory bowel disease (IBD). The aims of the present review were to reveal and analyze possible molecular pathways and consequences of the induction of an innate and adaptive immune response during infection with SARS-CoV-2 in patients with IBD. A thorough literature search was carried out by using the keywords: IBD, SARS-CoV-2, COVID-19. Based on the screening, a number of intracellular and extracellular pathways were considered and discussed, which can impact the immune response during SARS-CoV-2 infection in IBD patients. Additionally, the possible consequences of the infection for such patients were estimated. We further hypothesize that any virus, including the new SARS-CoV-2, infecting intestinal tissues and/or entering the host's body through receptors located on intestinal enterocytes may be a trigger for the onset of IBD in individuals with a genetic predisposition and/or the risk of developing IBD associated with other factors.


Assuntos
Imunidade Adaptativa , COVID-19/epidemiologia , Trato Gastrointestinal , Imunidade Inata , Doenças Inflamatórias Intestinais , COVID-19/imunologia , COVID-19/virologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/virologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Receptores Virais/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Internalização do Vírus
7.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198897

RESUMO

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV-Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.


Assuntos
Doença Celíaca/dietoterapia , Dieta , Glutens/metabolismo , Nanopartículas/uso terapêutico , Biópsia , Células CACO-2 , Doença Celíaca/imunologia , Doença Celíaca/metabolismo , Doença Celíaca/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Homeostase/imunologia , Humanos , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Nanopartículas/metabolismo , Triticum/efeitos adversos
8.
Int J Mol Sci ; 22(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34281249

RESUMO

Regenerating gene (REG) family proteins serve as multifunctional secretory molecules with trophic, antiapoptotic, anti-inflammatory, antimicrobial and probably immuno-regulatory effects. Since their discovery, accumulating evidence has clarified the potential roles of the REG family in the occurrence, progression and development of a wide range of inflammatory and inflammation-associated diseases of the gastrointestinal (GI) tract. However, significant gaps still exist due to the undefined nature of certain receptors, regulatory signaling pathways and possible interactions among distinct Reg members. In this narrative review, we first describe the structural features, distribution pattern and purported regulatory mechanisms of REG family proteins. Furthermore, we summarize the established and proposed roles of REG proteins in the pathogenesis of various inflammation-associated pathologies of the GI tract and the body as a whole, focusing particularly on carcinogenesis in the ulcerative colitis-colitic cancer sequence and gastric cancer. Finally, the clinical relevance of REG products in the context of diagnosis, treatment and prognostication are also discussed in detail. The current evidence suggests a need to better understanding the versatile roles of Reg family proteins in the pathogenesis of inflammatory-associated diseases, and their broadened future usage as therapeutic targets and prognostic biomarkers is anticipated.


Assuntos
Gastroenteropatias/metabolismo , Trato Gastrointestinal/metabolismo , Inflamação/imunologia , Animais , Apoptose/genética , Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Humanos , Inflamação/metabolismo , Doenças Inflamatórias Intestinais , Mucosa Intestinal/metabolismo , Lectinas Tipo C/metabolismo , Litostatina/genética , Litostatina/metabolismo , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Neoplasias Gástricas
9.
Nutrients ; 13(7)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206809

RESUMO

The gastrointestinal tract is a functionally and anatomically segmented organ that is colonized by microbial communities from birth. While the genetics of mouse gut development is increasingly understood, how nutritional factors and the commensal gut microbiota act in concert to shape tissue organization and morphology of this rapidly renewing organ remains enigmatic. Here, we provide an overview of embryonic mouse gut development, with a focus on the intestinal vasculature and the enteric nervous system. We review how nutrition and the gut microbiota affect the adaptation of cellular and morphologic properties of the intestine, and how these processes are interconnected with innate immunity. Furthermore, we discuss how nutritional and microbial factors impact the renewal and differentiation of the epithelial lineage, influence the adaptation of capillary networks organized in villus structures, and shape the enteric nervous system and the intestinal smooth muscle layers. Intriguingly, the anatomy of the gut shows remarkable flexibility to nutritional and microbial challenges in the adult organism.


Assuntos
Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Imunidade Inata , Morfogênese/fisiologia , Estado Nutricional , Simbiose/fisiologia , Animais , Dieta Hiperlipídica , Endotélio/imunologia , Sistema Nervoso Entérico , Células Epiteliais/imunologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Homeostase , Humanos , Mucosa Intestinal/imunologia , Camundongos
10.
Viruses ; 13(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209711

RESUMO

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH.


Assuntos
Coinfecção/virologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/imunologia , Infecções por HIV/virologia , Vacinas/imunologia , Animais , Fármacos Anti-HIV/uso terapêutico , Ensaios Clínicos como Assunto , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Imunossenescência , Inflamação , Infecção Latente/imunologia , Infecção Latente/virologia , Camundongos , Vacinas/administração & dosagem
11.
Nutrients ; 13(6)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204288

RESUMO

BACKGROUND: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. METHODS: Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. RESULTS: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1ß (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. CONCLUSIONS: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.


Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação , Triglicerídeos/administração & dosagem , Animais , Bactérias/classificação , Colectomia , Doença de Crohn , Citocinas/metabolismo , Disbiose , Ácidos Graxos Voláteis , Fezes , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Íleo , Doenças Inflamatórias Intestinais , Intestino Grosso , Intestino Delgado , Masculino , Camundongos
12.
Infect Immun ; 89(10): e0020521, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34227838

RESUMO

Chlamydia is known to both ascend to the upper genital tract and spread to the gastrointestinal tract following intravaginal inoculation. Gastrointestinal Chlamydia was recently reported to promote chlamydial pathogenicity in the genital tract since mice intravaginally inoculated with an attenuated Chlamydia strain, which alone failed to develop pathology in the genital tract, were restored to develop hydrosalpinx by intragastric coinoculation with wild-type Chlamydia. Gastrointestinal Chlamydia promoted hydrosalpinx via an indirect mechanism since Chlamydia in the gut did not directly spread to the genital tract lumen. In the current study, we further investigated the role of CD8+ T cells in the promotion of hydrosalpinx by gastrointestinal Chlamydia. First, we confirmed that intragastric coinoculation with wild-type Chlamydia promoted hydrosalpinx in mice that were inoculated with an attenuated Chlamydia strain in the genital tract 1 week earlier. Second, the promotion of hydrosalpinx by intragastrically coinoculated Chlamydia was blocked by depleting CD8+ T cells. Third, adoptive transfer of gastrointestinal Chlamydia-induced CD8+ T cells was sufficient for promoting hydrosalpinx in mice that were intravaginally inoculated with an attenuated Chlamydia strain. These observations have demonstrated that CD8+ T cells induced by gastrointestinal Chlamydia are both necessary and sufficient for promoting hydrosalpinx in the genital tract. The study has laid a foundation for further revealing the mechanisms by which Chlamydia-induced T lymphocyte responses (as a 2nd hit) promote hydrosalpinx in mice with genital Chlamydia-triggered tubal injury (as a 1st hit), a continuing effort in testing the two-hit hypothesis as a chlamydial pathogenic mechanism.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Chlamydia/imunologia , Chlamydia/patogenicidade , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Genitália Feminina/imunologia , Infecções do Sistema Genital/imunologia , Transferência Adotiva/métodos , Animais , Linfócitos T CD8-Positivos/microbiologia , Linhagem Celular Tumoral , Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Modelos Animais de Doenças , Feminino , Genitália Feminina/microbiologia , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos CBA , Infecções do Sistema Genital/microbiologia
13.
Indian J Pathol Microbiol ; 64(Supplement): S58-S62, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34135139

RESUMO

Gastro-intestinal (GI) lesions are common outcome to diverse etiological agents affecting the GI tract. It requires significant expertise to accurately diagnose the fundamental cause and treat accordingly. A better understanding of the immunological underpinning of these lesions is of great importance to ensure their successful management. Availability of specific animal models allows us to understand the subtle differences among diverse disease conditions and help decide upon the treatment trajectories. Since murine models are best suited for studying the immunopathogenesis of any disease, we will restrict our discussions here to the available murine models and their applications to study gastrointestinal lesions. In this review, we have systematically examined and compared the variety of mice models that are routinely used to study Inflammatory Bowel disease (IBD) and also how they can be leveraged to address specific questions relating to IBD.


Assuntos
Modelos Animais de Doenças , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos , Animais , Humanos
14.
Front Immunol ; 12: 683068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135909

RESUMO

Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer's disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.


Assuntos
Doença de Alzheimer/etiologia , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Imunomodulação , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Animais , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Disbiose , Retroalimentação Fisiológica , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo
15.
Toxins (Basel) ; 13(6)2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070838

RESUMO

This study investigated the impact of deoxynivalenol (DON) from naturally contaminated feed on pig growth, immune status, organ health, brain serotonin (5-Hydroxytryptamine, 5-HT) and behavior. Sixteen individually housed pigs (25.57 ± 0.98 kg, age 9 weeks) were randomly allotted to two dietary treatments: without DON (CON) or with 3.8 mg/kg of DON (MT). Pigs were pair-fed to eliminate differences in feed intake (equal tryptophan (Trp) intake). Pigs fed CON received a daily ration based on the ad libitum feed consumption of their MT pair-mate. Performance was determined over 21 days and blood collected for immunological and oxidative stress parameters. Behavior was recorded for 12 h on days 0, 7, 14 and 21. After 21 days, pigs were euthanized to collect tissues for immune parameters, gut morphology and brain serotonin levels. Overall, pigs fed MT had greater weight gain compared with CON. Immunological and oxidative stress parameters were unaffected, but pigs fed MT had reduced villus height, crypt depth and villus-to-crypt ratio in the jejunum. Pigs consuming MT had reduced concentration of 5-HT and increased 5-HT turnover in the hypothalamus. Mycotoxin-fed pigs spent more time lying and sitting, and less time standing and drinking. In conclusion, consumption of DON impacted gastrointestinal tract structure, altered behavior and changed Trp metabolism through increasing 5-HT turnover in hypothalamus.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Contaminação de Alimentos , Trato Gastrointestinal/efeitos dos fármacos , Tricotecenos/toxicidade , Triptofano/metabolismo , Zea mays/microbiologia , Ração Animal , Animais , Encéfalo/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Masculino , Estresse Oxidativo , Condicionamento Físico Animal , Suínos
16.
PLoS Pathog ; 17(5): e1009565, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33970966

RESUMO

Here, we assessed the efficacy of a short-course multimodal therapy (enrofloxacin, azithromycin, fenbendazole, and paromomycin) to eliminate common macaque endemic pathogens (EPs) and evaluated its impact on gastrointestinal (GI) microbiota, mucosal integrity, and local and systemic inflammation in sixteen clinically healthy macaques. Treatment combined with expanded practices resulted in successful maintenance of rhesus macaques (RM) free of common EPs, with no evidence of overt microbiota diversity loss or dysbiosis and instead resulted in a more defined luminal microbiota across study subjects. Creation of a GI pathogen free (GPF) status resulted in improved colonic mucosal barrier function (histologically, reduced colonic MPO+, and reduced pan-bacterial 16s rRNA in the MLN), reduced local and systemic innate and adaptive inflammation with reduction of colonic Mx1 and pSTAT1, decreased intermediate (CD14+CD16+) and non-classical monocytes (CD14-CD16+), reduced populations of peripheral dendritic cells, Ki-67+ and CD38+ CD4+ T cells, Ki-67+IgG+, and Ki-67+IgD+ B cells indicating lower levels of background inflammation in the distal descending colon, draining mesenteric lymph nodes, and systemically in peripheral blood, spleen, and axillary lymph nodes. A more controlled rate of viral acquisition resulted when untreated and treated macaques were challenged by low dose intrarectal SIVmac239x, with an ~100 fold increase in dose required to infect 50% (AID50) of the animals receiving treatment compared to untreated controls. Reduction in and increased consistency of number of transmitted founder variants resulting from challenge seen in the proof of concept study directly correlated with post-treatment GPF animal's improved barrier function and reduction of key target cell populations (Ki-67+ CD4+T cells) at the site of viral acquisition in the follow up study. These data demonstrate that a therapeutic and operational strategy can successfully eliminate varying background levels of EPs and their associated aberrant immunomodulatory effects within a captive macaque cohort, leading to a more consistent, better defined and reproducible research model.


Assuntos
Inflamação/terapia , Microbiota/efeitos dos fármacos , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Vírus da Imunodeficiência Símia/imunologia , Imunidade Adaptativa , Animais , Linfócitos B , Linfócitos T CD4-Positivos , Proliferação de Células , Terapia Combinada , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Imunidade Inata , Mucosa Intestinal , Linfonodos , Macaca mulatta , Masculino , Monócitos , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
17.
Front Immunol ; 12: 683022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054875

RESUMO

The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate's immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake.


Assuntos
Desenvolvimento Infantil , Sistema Imunitário/imunologia , Microbiota , Leite/microbiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Meio Ambiente , Feminino , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Idade Gestacional , Humanos , Sistema Imunitário/metabolismo , Imunidade Inata , Recém-Nascido , Microbiota/imunologia , Leite/imunologia , Gravidez
18.
Front Immunol ; 12: 666088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012449

RESUMO

The intestine harbors a complex community of bacterial species collectively known as commensal microbiota. Specific species of resident bacteria, as known as pathobiont, have pathogenic potential and can induce apparent damage to the host and intestinal inflammation in a certain condition. However, the host immune factors that permit its commensalism under steady state conditions are not clearly understood. Here, we studied the gut fitness of Listeria monocytogenes by using germ-free (GF) mice orally infected with this food-borne pathogen. L. monocytogenes persistently exists in the gut of GF mice without inducing chronic immunopathology. L. monocytogenes at the late phase of infection is not capable of infiltrating through the intestinal barrier. L. monocytogenes established the commensalism through the reversible down regulation of virulence gene expression. CD8+ T cells were found to be sufficient for the commensalism of L. monocytogenes. CD8+ T cells responding to L. monocytogenes contributed to the down-regulation of virulence gene expression. Our data provide important insights into the host-microbe interaction and have implications for developing therapeutics against immune disorders induced by intestinal pathogens or pathobionts.


Assuntos
Regulação Bacteriana da Expressão Gênica , Vida Livre de Germes , Listeria monocytogenes/fisiologia , Simbiose , Animais , Linfócitos T CD8-Positivos/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes/imunologia , Interações entre Hospedeiro e Microrganismos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Listeria monocytogenes/genética , Listeria monocytogenes/patogenicidade , Camundongos , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Virulência/genética
19.
Front Cell Infect Microbiol ; 11: 590874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791231

RESUMO

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.


Assuntos
COVID-19/patologia , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Imunidade Inata/imunologia , Enzima de Conversão de Angiotensina 2/biossíntese , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Bactérias/metabolismo , COVID-19/terapia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Expressão Gênica/genética , Humanos , Complexo Antígeno L1 Leucocitário/biossíntese , Obesidade/patologia , Probióticos/farmacologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
20.
Acta Med Indones ; 53(1): 96-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33818412

RESUMO

SARS-CoV-2 is a virus that can enter its hosts through the Angiotensin Converting Enzyme-2 (ACE2) receptor. ACE2 is mainly expressed in cells of the gastrointestinal tract, such as the esophageal epithelium and enterocytes from the ileum-colon. Coronavirus Disease 2019 (COVID-19) has varying clinical symptoms and presents differently in individuals, ranging from asymptomatic carriers to moderate clinical spectrum with mild pneumonia clinical features, and to a severe clinical presentation with dyspnea and hypoxia, leading to death due to respiratory or multi-organ failure. COVID-19 infection can also manifest themselves in the form of gastrointestinal symptoms such as diarrhea, vomiting, nausea, and abdominal pain. Severe complications of gastrointestinal COVID-19 infections include hemorrhage or perforation of the gastrointestinal tract and severe inflammation, which can adversely affect the intestinal immune system, and therefore the systemic immune system of the host. Furthermore, COVID-19 has also shown to affect microbiota homeostasis in the digestive tract. To date, no clear explanation is available regarding the pathophysiology of gastrointestinal SARS-CoV-2 infection, fecal RNA detection, and the possibility of fecal-oral transmission of SARS-CoV-2. This review aims to discuss the effects of SARS-CoV-2 infection on the digestive tract, microbiota, and lung, and the possibility of fecal-oral transmission in COVID-19.


Assuntos
COVID-19 , Gastroenteropatias , Trato Gastrointestinal , SARS-CoV-2 , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/prevenção & controle , COVID-19/transmissão , Fezes/virologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/virologia , Humanos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...