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1.
Front Immunol ; 12: 765965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721437

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome's potential as a biomarker and therapeutic target.


Assuntos
COVID-19/microbiologia , Síndrome da Liberação de Citocina/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , SARS-CoV-2/fisiologia , COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Disbiose/imunologia , Humanos , Imunidade , Inflamação
2.
Biomed Res Int ; 2021: 7880448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651049

RESUMO

COVID-19-associated neuropsychiatric complications are soaring. There is an urgent need to understand the link between COVID-19 and neuropsychiatric disorders. To that end, this article addresses the premise that SARS-CoV-2 infection results in gut dysbiosis and an altered microbiota-gut-brain (MGB) axis that in turn contributes to the neuropsychiatric ramifications of COVID-19. Altered MGB axis activity has been implicated independently as a risk of neuropsychiatric disorders. A review of the changes in gut microbiota composition in individual psychiatric and neurological disorders and gut microbiota in COVID-19 patients revealed a shared "microbial signature" characterized by a lower microbial diversity and richness and a decrease in health-promoting anti-inflammatory commensal bacteria accompanied by an increase in opportunistic proinflammatory pathogens. Notably, there was a decrease in short-chain fatty acid (SCFA) producing bacteria. SCFAs are key bioactive microbial metabolites with anti-inflammatory functions and have been recognized as a critical signaling pathway in the MGB axis. SCFA deficiency is associated with brain inflammation, considered a cardinal feature of neuropsychiatric disorders. The link between SARS-CoV-2 infection, gut dysbiosis, and altered MGB axis is further supported by COVID-19-associated gastrointestinal symptoms, a high number of SARS-CoV-2 receptors, angiotensin-cleaving enzyme-2 (ACE-2) in the gut, and viral presence in the fecal matter. The binding of SARS-CoV-2 to the receptor results in ACE-2 deficiency that leads to decreased transport of vital dietary components, gut dysbiosis, proinflammatory gut status, increased permeability of the gut-blood barrier (GBB), and systemic inflammation. More clinical research is needed to substantiate further the linkages described above and evaluate the potential significance of gut microbiota as a diagnostic tool. Meanwhile, it is prudent to propose changes in dietary recommendations in favor of a high fiber diet or supplementation with SCFAs or probiotics to prevent or alleviate the neuropsychiatric ramifications of COVID-19.


Assuntos
COVID-19/psicologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Bactérias/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , COVID-19/metabolismo , COVID-19/microbiologia , COVID-19/virologia , Dieta , Disbiose , Fezes/microbiologia , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação , Probióticos/farmacologia , SARS-CoV-2/isolamento & purificação
3.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638770

RESUMO

The gut microbiota (GM) is considered to constitute a powerful "organ" capable of influencing the majority of the metabolic, nutritional, physiological, and immunological processes of the human body. To date, five microbial-mediated mechanisms have been revealed that either endorse or inhibit tumorigenesis. Although the gastrointestinal and respiratory tracts are distant physically, they have common embryonic origin and similarity in structure. The lung microbiota is far less understood, and it is suggested that the crosslink between the human microbiome and lung cancer is a complex, multifactorial relationship. Several pathways linking their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Regarding implications of specific GM in lung cancer therapy, a few studies showed that the GM considerably affects immune checkpoint inhibitor (ICI) therapy by altering the differentiation of regulatory T cells and thus resulting in changes in immunomodulation mechanisms, as discovered by assessing drug metabolism directly and by assessing the host immune modulation response. Additionally, the GM may increase the efficacy of chemotherapeutic treatment in lung cancer. The mechanism underlying the role of the GLA in the pathogenesis and progression of lung cancer and its capability for diagnosis, manipulation, and treatment need to be further explored.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares , Linfócitos T Reguladores/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/terapia , Linfócitos T Reguladores/patologia
4.
Nutrients ; 13(10)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34684638

RESUMO

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient's microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.


Assuntos
Microbioma Gastrointestinal/imunologia , Sistema Imunitário/microbiologia , Fenômenos Fisiológicos da Nutrição/imunologia , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/microbiologia , Humanos , Rim/imunologia , Rim/microbiologia
5.
Nat Commun ; 12(1): 5751, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599171

RESUMO

While the major virulence factors for Vibrio cholerae, the cause of the devastating diarrheal disease cholera, have been extensively studied, the initial intestinal colonization of the bacterium is not well understood because non-human adult animals are refractory to its colonization. Recent studies suggest the involvement of an interbacterial killing device known as the type VI secretion system (T6SS). Here, we tested the T6SS-dependent interaction of V. cholerae with a selection of human gut commensal isolates. We show that the pathogen efficiently depleted representative genera of the Proteobacteria in vitro, while members of the Enterobacter cloacae complex and several Klebsiella species remained unaffected. We demonstrate that this resistance against T6SS assaults was mediated by the production of superior T6SS machinery or a barrier exerted by group I capsules. Collectively, our data provide new insights into immunity protein-independent T6SS resistance employed by the human microbiota and colonization resistance in general.


Assuntos
Cólera/microbiologia , Enterobacter cloacae/imunologia , Microbioma Gastrointestinal/imunologia , Klebsiella/imunologia , Sistemas de Secreção Tipo VI/metabolismo , Cápsulas Bacterianas/imunologia , Cápsulas Bacterianas/metabolismo , Cólera/imunologia , Resistência à Doença/imunologia , Enterobacter cloacae/metabolismo , Humanos , Klebsiella/metabolismo , Vibrio cholerae/imunologia , Vibrio cholerae/patogenicidade , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismo
6.
Front Immunol ; 12: 674803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594321

RESUMO

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.


Assuntos
Imunidade , Interleucina-17/sangue , Pancreatite/epidemiologia , Pancreatite/imunologia , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal/imunologia , Humanos , Interleucina-17/antagonistas & inibidores , Camundongos , Terapia de Alvo Molecular/métodos , Pancreatite/tratamento farmacológico , Fatores de Risco , Células Th17/imunologia , Resultado do Tratamento
7.
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
8.
Nat Commun ; 12(1): 5958, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645820

RESUMO

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/imunologia , Tolerância Imunológica , Hipersensibilidade Respiratória/microbiologia , Alérgenos/efeitos adversos , Animais , Bacteroides/isolamento & purificação , Bacteroides/metabolismo , Bifidobacterium longum/isolamento & purificação , Bifidobacterium longum/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Clostridiales/isolamento & purificação , Clostridiales/metabolismo , Alérgenos Animais/efeitos adversos , Alérgenos Animais/imunologia , Ovos/efeitos adversos , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/metabolismo , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Masculino , Leite/efeitos adversos , Leite/imunologia , Nozes/efeitos adversos , Nozes/imunologia , Pólen/química , Pólen/imunologia , Prunus persica/química , Prunus persica/imunologia , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/imunologia , Urease/biossíntese
9.
PLoS Pathog ; 17(10): e1009970, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34597344

RESUMO

Toxoplasma gondii is an orally acquired pathogen that induces strong IFN-γ based immunity conferring protection but that can also be the cause of immunopathology. The response in mice is driven in part by well-characterized MyD88-dependent signaling pathways. Here we focus on induction of less well understood immune responses that do not involve this Toll-like receptor (TLR)/IL-1 family receptor adaptor molecule, in particular as they occur in the intestinal mucosa. Using eYFP-IL-12p40 reporter mice on an MyD88-/- background, we identified dendritic cells, macrophages, and neutrophils as cellular sources of MyD88-independent IL-12 after peroral T. gondii infection. Infection-induced IL-12 was lower in the absence of MyD88, but was still clearly above noninfected levels. Overall, this carried through to the IFN-γ response, which while generally decreased was still remarkably robust in the absence of MyD88. In the latter mice, IL-12 was strictly required to induce type I immunity. Type 1 and type 3 innate lymphoid cells (ILC), CD4+ T cells, and CD8+ T cells each contributed to the IFN-γ pool. We report that ILC3 were expanded in infected MyD88-/- mice relative to their MyD88+/+ counterparts, suggesting a compensatory response triggered by loss of MyD88. Furthermore, bacterial flagellin and Toxoplasma specific CD4+ T cell populations in the lamina propria expanded in response to infection in both WT and KO mice. Finally, we show that My88-independent IL-12 and T cell mediated IFN-γ production require the presence of the intestinal microbiota. Our results identify MyD88-independent intestinal immune pathways induced by T. gondii including myeloid cell derived IL-12 production, downstream type I immunity and IFN-γ production by ILC1, ILC3, and T lymphocytes. Collectively, our data reveal an underlying network of immune responses that do not involve signaling through MyD88.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas/imunologia , Subunidade p40 da Interleucina-12/imunologia , Toxoplasmose Animal/imunologia , Animais , Mucosa Intestinal/imunologia , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/deficiência , Receptores Toll-Like/imunologia , Toxoplasma/imunologia
10.
Expert Rev Gastroenterol Hepatol ; 15(11): 1281-1294, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34654347

RESUMO

INTRODUCTION: Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED: This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION: Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Sistema Imunitário/imunologia , Pneumonia Viral/imunologia , Humanos , SARS-CoV-2
11.
FASEB J ; 35(10): e21888, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34473368

RESUMO

Endogenous tryptophan metabolism pathways lead to the production of serotonin (5-hydroxytryptamine; 5-HT), kynurenine, and several downstream metabolites which are involved in a multitude of immunological functions in both health and disease states. Ingested tryptophan is largely shunted to the kynurenine pathway (95%) while only minor portions (1%-2%) are sequestered for 5-HT production. Though often associated with the functioning of the central nervous system, significant production of 5-HT, kynurenine and their downstream metabolites takes place within the gut. Accumulating evidence suggests that these metabolites have essential roles in regulating immune cell function, intestinal inflammation, as well as in altering the production and suppression of inflammatory cytokines. In addition, both 5-HT and kynurenine have a considerable influence on gut microbiota suggesting that these metabolites impact host physiology both directly and indirectly via compositional changes. It is also now evident that complex interactions exist between the two pathways to maintain gut homeostasis. Alterations in 5-HT and kynurenine are implicated in the pathogenesis of many gastrointestinal dysfunctions, including inflammatory bowel disease. Thus, these pathways present numerous potential therapeutic targets, manipulation of which may aid those suffering from gastrointestinal disorders. This review aims to update both the role of 5-HT and kynurenine in immune regulation and intestinal inflammation, and analyze the current knowledge of the relationship and interactions between 5-HT and kynurenine pathways.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Cinurenina/imunologia , Serotonina/imunologia , Transdução de Sinais/imunologia , Triptofano/imunologia , Animais , Humanos , Inflamação/imunologia , Inflamação/patologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia
12.
Front Immunol ; 12: 671331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566952

RESUMO

The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Interleucinas/imunologia , Células Th17/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Interleucinas/biossíntese , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Salmonella typhi , Células Th17/metabolismo , Febre Tifoide/imunologia , Febre Tifoide/microbiologia
13.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578858

RESUMO

The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the disease coronavirus disease 2019 (COVID-19). The cumulative number of cases reported globally is now nearly 197 million and the number of cumulative deaths is 4.2 million (26 July to 1 August 2021). Currently we are focusing primarily on keeping a safe distance from others, washing our hands, and wearing masks, and the question of the effects of diet and diet-dependent risk factors remains outside the center of attention. Nevertheless, numerous studies indicate that diet can play an important role in the course of COVID-19. In this paper, based on select scientific reports, we discuss the structure and replication cycle of SARS-CoV-2, risk factors, dietary standards for sick patients, and the roles of the microbiome and dietary components supporting the immune system in preventing COVID-19.


Assuntos
COVID-19/dietoterapia , Comportamento Alimentar , Microbioma Gastrointestinal/imunologia , Apoio Nutricional/métodos , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Humanos , Micronutrientes/administração & dosagem , Probióticos/administração & dosagem , Fatores de Risco , Índice de Gravidade de Doença , Replicação Viral/imunologia
14.
J Immunol ; 207(8): 2179-2191, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34497150

RESUMO

Gut microbes play an important role in the development of host B cells. It has been controversial whether GALT is the development site of B cells in pigs. By investigating the relationship between gut microbes and the development of B cells in the GALT of piglets, we found, to our knowledge for the first time, that early B cells exist in the gut lamina propria (LP) in pigs at different ages. We further used Lactobacillus rhamnosus GG (LGG) to treat piglets. The results showed that LGG promotes the development of the early B lineage, affects the composition of the Ig CDR3 repertoires of B cells, and promotes the production of IgA in the intestinal LP. Additionally, we found that the p40 protein derived from LGG can activate the EGFR/AKT and NF-κB signaling pathways, inducing porcine intestinal epithelial cells (IPEC-J2) to secrete a proliferation-inducing ligand (APRIL), which promotes IgA production in B cells. Finally, we identified ARF4 and DIF3 as candidates for p40 receptors on IPEC-J2 by GST pull-down, liquid chromatography-mass spectrometry/mass spectrometry analysis, and coimmunoprecipitation. In conclusion, LGG could promote early B cell differentiation and development in the intestinal LP in piglets and might contribute to promoting IgA production via secretion of p40, which interacts with the membrane receptors on IPEC-J2 and induces them to secrete APRIL. Our study will provide insight to aid in better utilization of probiotics to increase human health.


Assuntos
Linfócitos B/imunologia , Proteínas de Bactérias/metabolismo , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/metabolismo , Mucosa Intestinal/patologia , Lactobacillus rhamnosus/imunologia , Membrana Mucosa/imunologia , Animais , Formação de Anticorpos , Diferenciação Celular , Linhagem Celular , Linhagem da Célula , Proteínas de Fluorescência Verde/metabolismo , NF-kappa B/metabolismo , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais , Suínos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
15.
Front Immunol ; 12: 685742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512624

RESUMO

Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs may interfere in these processes, they constitute the most frequently prescribed medication during pregnancy to prohibit detrimental consequences of infections. Gestational antibiotic intervention is linked to preeclampsia and negative effects on neonatal immunity. Even though perturbations in the immune system of the mother can affect reproductive health, the impact of microbial manipulation on maternal immunity is still unknown. Aim: To assess whether antibiotic treatment influences maternal immunity during pregnancy. Methods: Pregnant mice were treated with broad-spectrum antibiotics. The maternal gut microbiome was assessed. Numerous immune parameters throughout the maternal body, including placenta and amniotic fluid were investigated and a novel machine-learning ensemble strategy was used to identify immunological parameters that allow distinction between the control and antibiotic-treated group. Results: Antibiotic treatment reduced diversity of maternal microbiota, but litter sizes remained unaffected. Effects of antibiotic treatment on immunity reached as far as the placenta. Four immunological features were identified by recursive feature selection to contribute to the most robust classification (splenic T helper 17 cells and CD5+ B cells, CD4+ T cells in mesenteric lymph nodes and RORγT mRNA expression in placenta). Conclusion: In the present study, antibiotic treatment was able to affect the carefully coordinated immunity during pregnancy. These findings highlight the importance of inclusion of immunological parameters when studying the effects of medication used during gestation.


Assuntos
Imunidade Adaptativa/imunologia , Animais Recém-Nascidos/imunologia , Anticorpos Antibacterianos/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Animais , Animais Recém-Nascidos/microbiologia , Antibacterianos/farmacologia , Feminino , Microbioma Gastrointestinal/genética , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Intestinos/microbiologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Gravidez
16.
Mil Med Res ; 8(1): 50, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503577

RESUMO

By its nature, Gulf war illness (GWI) is multisymptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation, pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war (GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies, which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.


Assuntos
Gastroenteropatias/etiologia , Síndrome do Golfo Pérsico/complicações , Sistema Nervoso Entérico/efeitos dos fármacos , Sistema Nervoso Entérico/fisiopatologia , Gastroenteropatias/fisiopatologia , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Humanos , Síndrome do Golfo Pérsico/fisiopatologia , Veteranos/estatística & dados numéricos
17.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578853

RESUMO

Human milk serves as a model for infant formula providing nutritional solutions for infants not able to receive enough mother's milk. Infant formulas aim to mimic the composition and functionality of human milk by providing ingredients reflecting those of the latest human milk insights, such as prebiotics, probiotics and postbiotics. The aim of this study was to examine the effects of the supplementation with a postbiotic (LactofidusTM) and its combination with the prebiotics short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) in a preclinical model of healthy suckling rats. Pups were supplemented daily with LactofidusTM (POST group) and/or scGOS/lcFOS (P+P and PRE groups, respectively). Body weight and fecal consistency were analyzed. At the end of the study, immunoglobulin (Ig) profile, intestinal gene expression, microbiota composition and short chain fatty acid (SCFA) proportion were quantified. The supplementation with all nutritional interventions modulated the Ig profile, but the prebiotic mixture and the postbiotic induced differential effects: whereas scGOS/lcFOS induced softer feces and modulated microbiota composition and SCFA profile, Lactofidus™ upregulated Toll-like receptors gene expression. The use of the combination of scGOS/lcFOS and Lactofidus™ showed the effects observed for the oligosaccharides separately, as well as showing a synergistic impact on animal growth. Thus, the combined use of both products seems to be a good strategy to modulate immune and microbial features in early life.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Animais , Animais Recém-Nascidos , Modelos Animais , Prebióticos/microbiologia , Ratos
18.
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
19.
Nat Commun ; 12(1): 4907, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389726

RESUMO

The intestinal mucosa constitutes an environment of closely regulated immune cells. Dendritic cells (DC) interact with the gut microbiome and antigens and are important in maintaining gut homeostasis. Here, we investigate DC transcriptome, phenotype and function in five anatomical locations of the gut lamina propria (LP) which constitute different antigenic environments. We show that DC from distinct gut LP compartments induce distinct T cell differentiation and cytokine secretion. We also find that PD-L1+ DC in the duodenal LP and XCR1+ DC in the colonic LP comprise distinct tolerogenic DC subsets that are crucial for gut homeostasis. Mice lacking PD-L1+ and XCR1+ DC have a proinflammatory gut milieu associated with an increase in Th1/Th17 cells and a decrease in Treg cells and have exacerbated disease in the models of 5-FU-induced mucositis and DSS-induced colitis. Our findings identify PD-L1+ and XCR1+ DC as region-specific physiologic regulators of intestinal homeostasis.


Assuntos
Antígeno B7-H1/imunologia , Células Dendríticas/imunologia , Homeostase/imunologia , Mucosa Intestinal/imunologia , Receptores de Quimiocinas/imunologia , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Colite/genética , Colite/imunologia , Colite/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Homeostase/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transcriptoma/genética , Transcriptoma/imunologia
20.
Expert Rev Mol Med ; 23: e7, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34340720

RESUMO

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality - both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.


Assuntos
COVID-19/epidemiologia , Microbioma Gastrointestinal/imunologia , Imunidade/genética , Pandemias , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Epigênese Genética , Feminino , Humanos , Masculino , Receptores Virais/genética , Fatores Sexuais , Resultado do Tratamento
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