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1.
Biomed Res Int ; 2021: 6670798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681368

RESUMO

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic with millions of infected patients. Alteration in humans' microbiota was also reported in COVID-19 patients. The alteration in human microbiota may contribute to bacterial or viral infections and affect the immune system. Moreover, human's microbiota can be altered due to SARS-CoV-2 infection, and these microbiota changes can indicate the progression of COVID-19. While current studies focus on the gut microbiota, it seems necessary to pay attention to the lung microbiota in COVID-19. This study is aimed at reviewing respiratory microbiota dysbiosis among COVID-19 patients to encourage further studies on the field for assessment of SARS-CoV-2 and respiratory microbiota interaction.


Assuntos
Disbiose , Pulmão , Micobioma/imunologia , /imunologia , /imunologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/virologia , Microbioma Gastrointestinal/imunologia , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/virologia
2.
Microbiome ; 9(1): 39, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549144

RESUMO

BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.


Assuntos
Antibacterianos/efeitos adversos , Colite/induzido quimicamente , Colite/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Colite/imunologia , Colite/patologia , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/imunologia , Humanos , Masculino , Metronidazol/farmacologia , Camundongos , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Estreptomicina/efeitos adversos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Vancomicina/efeitos adversos
3.
Nat Commun ; 12(1): 805, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547295

RESUMO

Efforts to improve the prognosis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) have suffered from poor understanding of its pathogenesis. Here we show that the pathogenesis of SR-Gut-aGVHD is associated with reduction of IFN-γ+ Th/Tc1 cells and preferential expansion of IL-17-IL-22+ Th/Tc22 cells. The IL-22 from Th/Tc22 cells causes dysbiosis in a Reg3γ-dependent manner. Transplantation of IFN-γ-deficient donor CD8+ T cells in the absence of CD4+ T cells produces a phenocopy of SR-Gut-aGVHD. IFN-γ deficiency in donor CD8+ T cells also leads to a PD-1-dependent depletion of intestinal protective CX3CR1hi mononuclear phagocytes (MNP), which also augments expansion of Tc22 cells. Supporting the dual regulation, simultaneous dysbiosis induction and depletion of CX3CR1hi MNP results in full-blown Gut-aGVHD. Our results thus provide insights into SR-Gut-aGVHD pathogenesis and suggest the potential efficacy of IL-22 antagonists and IFN-γ agonists in SR-Gut-aGVHD therapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Disbiose/imunologia , Doença Enxerto-Hospedeiro/imunologia , Interferon gama/imunologia , Interleucinas/imunologia , Fagócitos/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/transplante , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/imunologia , Modelos Animais de Doenças , Disbiose/genética , Disbiose/microbiologia , Disbiose/patologia , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/microbiologia , Doença Enxerto-Hospedeiro/patologia , Interferon gama/deficiência , Interferon gama/genética , Interleucina-17/deficiência , Interleucina-17/genética , Interleucina-17/imunologia , Interleucinas/genética , Intestinos/imunologia , Intestinos/microbiologia , Intestinos/patologia , Depleção Linfocítica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/imunologia , Fagócitos/citologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores , Linfócitos T Reguladores , Irradiação Corporal Total
4.
J Med Case Rep ; 15(1): 60, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557941

RESUMO

BACKGROUND: To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. CASE PRESENTATION: A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT. CONCLUSIONS: After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.


Assuntos
Subpopulações de Linfócitos B , Disbiose/terapia , Transplante de Microbiota Fecal , Gastroenteropatias/terapia , Microbioma Gastrointestinal , Idoso , Bacteroidetes , Bifidobacterium , Disbiose/microbiologia , Faecalibacterium , Feminino , Gastroenteropatias/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Proteobactérias , Adulto Jovem
5.
Am J Chin Med ; 49(2): 237-268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622213

RESUMO

Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Disbiose/microbiologia , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Doenças Autoimunes/microbiologia , Doenças Autoimunes/terapia , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus/microbiologia , Diabetes Mellitus/terapia , Eletroacupuntura , Gastroenteropatias/microbiologia , Gastroenteropatias/terapia , Humanos , Doenças Metabólicas/microbiologia , Doenças Metabólicas/terapia , Neoplasias/microbiologia , Neoplasias/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/microbiologia , Obesidade/terapia , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/terapia
6.
Gene ; 779: 145510, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33600956

RESUMO

The human gut microbiota in long-living people has been characterized, however, its metabolic potential is still largely unknown in this group. In this study, the gut microbiota was assessed in 37 Chinese long-living participants (aged 90 + years) by metagenomic sequencing of stool samples. Participants were categorized into two groups, healthy long-living (n = 28) and unhealthy long-living (n = 9). Gut microbiota composition and function were compared among these two groups. We found that the gut microbiota in the healthy long-living group was significantly separated from the unhealthy group. The healthy long-living group contained a higher abundance of Bacteroidetes and more functional pathways in energy metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins, and biosynthesis of other secondary metabolites. The unhealthy group contained a higher abundance of Streptococcus and other pathogenic bacteria, and also contained more functional pathways for xenobiotics biodegradation and metabolism than the healthy group. Additionally, the unhealthy group had decreased levels of carbohydrate-active enzymes, including host-glycan and fiber degrading enzymes, and an increase in starch-degrading enzymes. In conclusion, the gut microbiota of unhealthy long-living people contains more pathogenic bacteria, and the overall gut microbiota may be in an unhealthy state, "dysbiosis", which leads to a decrease in carbohydrate digestion, glycan and thiamine (B1) metabolites, and fatty acid biosynthesis.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Idoso de 80 Anos ou mais , Aminoácidos/metabolismo , Grupo com Ancestrais do Continente Asiático , Metabolismo dos Carboidratos , Resistência Microbiana a Medicamentos/genética , Enzimas/genética , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Metagenoma , Streptococcus/patogenicidade , Fatores de Virulência/genética
7.
Mucosal Immunol ; 14(2): 296-304, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33500564

RESUMO

Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host's defense against viral respiratory infections. The gut microbiota's composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota's composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung-gut axis in coronavirus disease 2019.


Assuntos
Microbioma Gastrointestinal , Pulmão/imunologia , Animais , Dieta , Fibras na Dieta/metabolismo , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Imunidade nas Mucosas , Influenza Humana/imunologia , Probióticos , Vírus Sinciciais Respiratórios , Infecções Respiratórias
8.
Vet Clin North Am Small Anim Pract ; 51(1): 155-169, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33131916

RESUMO

The intestinal microbiome is an important immune and metabolic organ in health and disease. Recent molecular and metabolomic approaches have provided a better characterization of different types of dysbiosis, including mucosa-adherent bacteria and functional changes in the microbiome. This article summarizes recent advances in assessment of dysbiosis, the importance of the bile acid-converting Clostridium hiranonis as an important beneficial bacterium in the canine gut, and different therapeutic approaches to dysbiosis.


Assuntos
Doenças do Gato/microbiologia , Diarreia/veterinária , Doenças do Cão/microbiologia , Disbiose/veterinária , Microbioma Gastrointestinal , Animais , Gatos , Diarreia/microbiologia , Cães , Disbiose/microbiologia
9.
J Urol ; 205(1): 86-93, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856979

RESUMO

PURPOSE: The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging. MATERIALS AND METHODS: Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations. RESULTS: The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance of Veillonella (p=0.04) and Corynebacterium (p=0.03), and decreased Ruminococcus (p=0.03) compared to controls, with differences exacerbating with disease progression. Compared to catheterized urines, bladder cancer washouts showed the specific increase of some taxa, like Burkholderiaceae (p=0.014), whereas midstream urines were enriched in Streptococcus (p <0.0001), Enterococcus (p <0.0001), Corynebacterium (p=0.038) and Fusobacterium (p <0.0001). CONCLUSIONS: The bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.


Assuntos
Disbiose/diagnóstico , Microbiota/genética , Neoplasias da Bexiga Urinária/urina , Bexiga Urinária/microbiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA Bacteriano/isolamento & purificação , Disbiose/microbiologia , Disbiose/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , RNA Ribossômico 16S/genética , Urinálise/métodos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/patologia , Cateterismo Urinário/métodos
10.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375200

RESUMO

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut-liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.


Assuntos
Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Fígado/fisiologia , Animais , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/fisiopatologia , Trato Gastrointestinal/microbiologia , Hepatectomia/métodos , Humanos , Hepatopatias/fisiopatologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/fisiopatologia
11.
Front Cell Infect Microbiol ; 10: 576551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324572

RESUMO

Infection with the SARS-CoV-2 virus causes cardiopulmonary and vascular complications, ranging in severity. Understanding the pathogenic mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for its prevention and/or treatment. Virus microbiota reciprocal interactions have been studied in a variety of viral infections. For example, the integrity of Coronavirus particles can be disrupted by surfactin, a bacterial surface molecule that targets other viruses, including that of influenza A. In this light, intestinal microbiota likely influences COVID-19 virulence, while from its side SARS-CoV-2 may affect the intestinal microbiome promoting dysbiosis and other deleterious consequences. Hence, the microbiota pre-existing health status and its alterations in the course of SARS-CoV-2 infection, are likely to play an important, still underscored role in determining individual susceptibility and resilience to COVID-19. Indeed, the vast majority of COVID-19 worst clinical conditions and fatalities develop in subjects with specific risk factors such as aging and the presence of one or more comorbidities, which are intriguingly characterized also by unhealthy microbiome status. Moreover, these comorbidities require complex pharmacological regimens known as "polypharmacy" that may further affect microbiota integrity and worsen the resilience to viral infections. This complex situation may represent a further and underestimated risk with regard to COVID-19 clinical burden for the elderly and comorbid people. Here, we discuss the possible biological, physiopathological, and clinical implications of gut microbiota in COVID-19 and the strategies to improve/maintain its healthy status as a simple and adjunctive strategy to reduce COVID-19 virulence and socio-sanitary burden.


Assuntos
/microbiologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , /fisiologia , Fatores Etários , /fisiopatologia , Disbiose/microbiologia , Disbiose/virologia , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/virologia , Humanos , Interações Microbianas , Fatores de Risco , Virulência
12.
Anim Sci J ; 91(1): e13475, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33078490

RESUMO

Growth performance of pigs has been associated with healthy gut microbiota. To improve production, pigs are usually treated with antimicrobials. Nonetheless, while antimicrobials harm the gut-indigenous microbiota, probiotic supplementation seems to help keep it healthy. Here, using antimicrobials, we artificially induced dysbiosis in pigs and evaluated a possible preventive effect of probiotic supplementation. Three 6-week-old piglets were given a basal feed, and 3 more the feed supplemented with 2.0 × 106  CFU of Bacillus subtilis QST713/g of feed. After 14 days, antimicrobial enrofloxacin (5 mg/kg B.W.) was injected intramuscularly to all pigs on days 14-16. Feces were collected on days 14, 17, 19, 21, and 23. Total bacteria count was unaffected by enrofloxacin or QST713. However, Lactobacillus spp. and, in particular, Escherichia coli were affected by enrofloxacin, the latter not being observed in the feces on days 17 and 19. Interestingly, a reciprocal increase in E. coli was observed in control pigs on days 21 and 23, although in QST713-supplemented piglets, this increase was attenuated. While the gut microbiota composition did not return to initial levels in antimicrobial-administered piglets, it did in QST713-supplemented piglets. QST713 supplementation was likely crucial to keep the microbiota of piglets healthy.


Assuntos
Antibacterianos/efeitos adversos , Bacillus subtilis , Suplementos Nutricionais , Disbiose/prevenção & controle , Disbiose/veterinária , Enrofloxacina/efeitos adversos , Probióticos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Animais , Antibacterianos/administração & dosagem , Disbiose/induzido quimicamente , Disbiose/microbiologia , Enrofloxacina/administração & dosagem , Fezes/microbiologia , Microbioma Gastrointestinal , Injeções Intramusculares , Suínos , Doenças dos Suínos/induzido quimicamente , Doenças dos Suínos/microbiologia
13.
Rev Med Suisse ; 16(710): 1916-1919, 2020 Oct 14.
Artigo em Francês | MEDLINE | ID: mdl-33058577

RESUMO

Probiotics are a big food and pharmaceutical industry today. The most widely used probiotics are Lactobacillus spp, Bifidobacterium spp, strains of Enterococcus spp, Streptococcus spp and yeasts such as Saccharomyces pp. Among the best-known indications are Clostridioides difficile colitis and diarrhea due to antibiotics, but probiotics are also proposed as adjuvants for atopic syndromes, autoimmune diseases, prevention and treatment of obesity, diabetes and cystic fibrosis, where dysbiosis play an important role. However, their use remains debated due to a lack of powerful data proving their effectiveness and their often-overlooked side effects.


Assuntos
Probióticos/efeitos adversos , Probióticos/uso terapêutico , Antibacterianos/efeitos adversos , Diarreia/microbiologia , Diarreia/terapia , Disbiose/microbiologia , Disbiose/terapia , Humanos
14.
Nature ; 585(7826): 509-517, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32968260

RESUMO

Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium that is characterized by the accumulation of mutations and a dysregulated immune response. Up to 90% of disease risk is thought to be due to environmental factors such as diet, which is consistent with a growing body of literature that describes an 'oncogenic' CRC-associated microbiota. Whether this dysbiosis contributes to disease or merely represents a bystander effect remains unclear. To prove causation, it will be necessary to decipher which specific taxa or metabolites drive CRC biology and to fully characterize the underlying mechanisms. Here we discuss the host-microbiota interactions in CRC that have been reported so far, with particular focus on mechanisms that are linked to intestinal barrier disruption, genotoxicity and deleterious inflammation. We further comment on unknowns and on the outstanding challenges in the field, and how cutting-edge technological advances might help to overcome these. More detailed mechanistic insights into the complex CRC-associated microbiota would potentially reveal avenues that can be exploited for clinical benefit.


Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/fisiopatologia , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação/microbiologia , Mutagênese
15.
mSphere ; 5(5)2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938697

RESUMO

Hygienic measures imposed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contain COVID-19 have proven effective in controlling the pandemic. In this article, we argue that these measures could impact the human microbiome in two different and disparate ways, acting as a double-edged sword in human health. New lines of research have shown that the diversity of human intestinal and oropharyngeal microbiomes can shape pulmonary viral infection progression. Here, we suggest that the disruption in microbial sharing, as it is associated with dysbiosis (loss of bacterial diversity associated with an imbalance of the microbiota with deleterious consequences for the host), may worsen the prognosis of COVID-19 disease. In addition, social detachment can also decrease the rate of transmission of antibiotic-resistant bacteria. Therefore, it seems crucial to perform new studies combining the pandemic control of COVID-19 with the diversity of the human microbiome.


Assuntos
Biodiversidade , Infecções por Coronavirus/prevenção & controle , Microbiota , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Infecções por Coronavirus/mortalidade , Disbiose/microbiologia , Humanos , Pneumonia Viral/mortalidade , Rede Social
16.
Proc Natl Acad Sci U S A ; 117(40): 24998-25007, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958643

RESUMO

Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.


Assuntos
Anorexia/imunologia , Antígenos CD8/imunologia , Memória Imunológica/imunologia , Coriomeningite Linfocítica/imunologia , Viroses/imunologia , Animais , Anorexia/microbiologia , Anorexia/virologia , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/virologia , Firmicutes/imunologia , Firmicutes/metabolismo , Microbioma Gastrointestinal/imunologia , Humanos , Coriomeningite Linfocítica/microbiologia , Coriomeningite Linfocítica/patologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Camundongos , Linfócitos T/imunologia , Linfócitos T/microbiologia , Verrucomicrobia/imunologia , Verrucomicrobia/patogenicidade , Viroses/microbiologia , Viroses/patologia
17.
Phytomedicine ; 79: 153322, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920286

RESUMO

BACKGROUND: Gut-heart axis has emerged as a novel concept to provide new insights into the complex mechanisms of heart failure (HF) and offer new therapeutic targets. Cardiac hypertrophy (CH) is one of the etiological agents contributing to the development of HF. Baoyuan Decoction (BYD), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating CH and preventing HF. Previously, we have reported that BYD-targeted endogenous metabolites are potentially linked to gut microbiota metabolism, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of BYD remains to be elucidated. PURPOSE: To investigate whether the gut microbiota plays a key role in anti-CH effects of BYD. STUDY DESIGN: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and microflora suppression model was adopted to investigate the links between the microbiota-host metabolic interaction and BYD efficacy in CH rats. METHOD: Firstly, the efficacy evaluation of BYD in treating chronic isoproterenol (ISO)-induced CH rats was performed by using multiple pharmacodynamic approaches. Then, the fecal metabolomics and 16S rRNA sequencing techniques were used to obtain the microbial and metabolic features of BYD against CH. After that, the potential gut-heart axis-based mechanism of BYD against CH was predicted by bioinformatic network analysis and validated by multiple molecular biology approaches. Finally, the antibiotics (AB)-induced gut microbiota suppression was employed to investigate whether the anti-CH effects of BYD is associated with the gut microflora. RESULTS: The fecal microbial communities and metabolic compositions were significantly altered in ISO-induced CH rats, while BYD effectively ameliorated the CH-associated gut microbiota dysbiosis, especially of Firmicutes and Bacteroidetes, and time-dependently alleviated the disturbance of fecal metabolome and reversed the changes of key CH and gut microbiota-related metabolites, such as short/medium chain fatty acids, primary/secondary bile acids, and amino acids. The mechanism study showed that the anti-CH effect of BYD was related to inhibition of the derivatives of arginine and tryptophan and their downstream pro-hypertrophic, pro-inflammatory, and pro-oxidant signaling pathways. The following microflora suppression test showed that BYD-mediated myocardial protection was decreased either in pharmacodynamics or in metabolic modulation. CONCLUSION: This study demonstrates that the protection of BYD against CH is partially gut microbiota dependent, and the regulatory effects of gut metabolism-related tryptophan and arginine derivatives is an important cardioprotection mechanism of BYD.


Assuntos
Cardiomegalia/tratamento farmacológico , Cardiomegalia/microbiologia , Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Cardiomegalia/patologia , Disbiose/tratamento farmacológico , Disbiose/etiologia , Disbiose/microbiologia , Fezes/química , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Coração/efeitos dos fármacos , Isoproterenol/toxicidade , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley
18.
PLoS Biol ; 18(8): e3000788, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841232

RESUMO

Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. These experiments in mice also led to the discovery that F. nucleatum may also "give back" to the community by reinforcing sialidase activity, a biochemical feature of human dysbiosis. Using human vaginal bacterial communities, we show that F. nucleatum supported robust outgrowth of Gardnerella vaginalis, a major sialidase producer and one of the most abundant organisms in BV. These results illustrate that mutually beneficial relationships between vaginal bacteria support pathogen colonization and may help maintain features of dysbiosis. These findings challenge the simplistic dogma that the mere absence of "healthy" lactobacilli is the sole mechanism that creates a permissive environment for pathogens during vaginal dysbiosis. Given the ubiquity of F. nucleatum in the human mouth, these studies also suggest a possible mechanism underlying links between vaginal dysbiosis and oral sex.


Assuntos
Proteínas de Bactérias/genética , Disbiose/microbiologia , Fusobacterium/metabolismo , Gardnerella vaginalis/metabolismo , Neuraminidase/genética , Polissacarídeos/metabolismo , Vaginose Bacteriana/microbiologia , Animais , Proteínas de Bactérias/metabolismo , Técnicas de Tipagem Bacteriana , Disbiose/patologia , Feminino , Fusobacterium/genética , Fusobacterium/isolamento & purificação , Fusobacterium/patogenicidade , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Gardnerella vaginalis/patogenicidade , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microbiota/genética , Neuraminidase/metabolismo , RNA Ribossômico 16S/genética , Ácidos Siálicos/metabolismo , Simbiose/genética , Vagina/microbiologia , Vaginose Bacteriana/patologia
19.
Nat Commun ; 11(1): 4018, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782301

RESUMO

The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Consórcios Microbianos , Obesidade/microbiologia , Adulto , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Estudos de Coortes , Disbiose/metabolismo , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Especificidade de Hospedeiro , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Obesidade/metabolismo
20.
J Med Life ; 13(2): 200-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742514

RESUMO

The work assessed the state of the intestinal microbiocenosis in 52 puerperae at the in whom the pregnancy developed against the background of the metabolic syndrome. The diagnosis of metabolic syndrome was determined according to the criteria approved by the World Health Organization for pregnant women. The state of intestinal microbiocenosis was assessed by a bacteriological examination of feces immediately after delivery. The content of the main representatives of the obligate microflora (bifidobacteria, lactobacilli, native intestinal bacilli, fecal streptococci) and facultative (conditionally pathogenic) microorganisms (representatives of the genus Prоteus, Klebsiella, pathogenic strains of E. coli, Staphylococcus epidermidis, Enterobacter, Citrobacter, Clostridium difficile, Candida fungi) was determined. Cultures were made on appropriate growth media. At the time of birth, all patients of group I showed signs of intestinal microbiocenosis disorder. At the same time, 13 (54.2%) puerperae were diagnosed signs of dysbiosis of II degree, 9 (37.5%) with signs of III degree, which were generally characterized by a significant decrease in the content of the main representatives of obligate microflora (Bifidobacterium, Lactobacillus, Escherichia coli, Fecal streptococci) with simultaneous high contamination of Candida albicans and Clostridium difficile. So, it can be considered as a possible predictor of very early preterm birth in women with MS. In pregnant women with MS, but who gave timely birth (group II), dysbiotic disorders were detected to a lesser extent. Thus, in 13 (46.4%) patients, initial signs of intestinal dysbiosis (first degree) were detected in 4 (14.3%) patients (second degree). In 11 (39.3%) puerperae of group II, microbial indices indicated normal eubiotic ratios.


Assuntos
Disbiose/microbiologia , Disbiose/patologia , Intestinos/microbiologia , Intestinos/patologia , Síndrome Metabólica/complicações , Trabalho de Parto Prematuro/microbiologia , Adulto , Bifidobacterium/fisiologia , Escherichia coli/fisiologia , Fezes/microbiologia , Feminino , Humanos , Recém-Nascido , Lactobacillus/fisiologia , Gravidez , Adulto Jovem
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