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1.
Cell ; 175(4): 962-972.e10, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388453

RESUMO

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.


Assuntos
Povo Asiático , Emigração e Imigração , Microbioma Gastrointestinal , Adulto , Bacteroides/isolamento & purificação , Fibras na Dieta/metabolismo , Emigrantes e Imigrantes , Humanos , Metagenoma , Obesidade/epidemiologia , Obesidade/microbiologia , Prevotella/isolamento & purificação , Estados Unidos
2.
Immunity ; 50(3): 692-706.e7, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30824326

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a severe form of lung fibrosis with a high mortality rate. However, the etiology of IPF remains unknown. Here, we report that alterations in lung microbiota critically promote pulmonary fibrosis pathogenesis. We found that lung microbiota was dysregulated, and the dysregulated microbiota in turn induced production of interleukin-17B (IL-17B) during bleomycin-induced mouse lung fibrosis. Either lung-microbiota depletion or IL-17B deficiency ameliorated the disease progression. IL-17B cooperated with tumor necrosis factor-α to induce expression of neutrophil-recruiting genes and T helper 17 (Th17)-cell-promoting genes. Three pulmonary commensal microbes, which belong to the genera Bacteroides and Prevotella, were identified to promote fibrotic pathogenesis through IL-17R signaling. We further defined that the outer membrane vesicles (OMVs) that were derived from the identified commensal microbes induced IL-17B production through Toll-like receptor-Myd88 adaptor signaling. Together our data demonstrate that specific pulmonary symbiotic commensals can promote lung fibrosis by regulating a profibrotic inflammatory cytokine network.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/microbiologia , Interleucina-17/metabolismo , Pulmão/metabolismo , Pulmão/microbiologia , Microbiota/fisiologia , Animais , Bacteroides/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Neutrófilos/metabolismo , Prevotella/metabolismo , Transdução de Sinais/fisiologia , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
EMBO J ; 41(19): e110629, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-35968812

RESUMO

Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection.


Assuntos
Infecções por HIV , HIV-1 , Antivirais , Disbiose , Feminino , Humanos , Células de Langerhans , Prevotella
4.
EMBO J ; 40(23): e108287, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34676563

RESUMO

Prevotella copri is a prevalent inhabitant of the human gut and has been associated with plant-rich diet consumption and diverse health states. The underlying genetic basis of these associations remains enigmatic due to the lack of genetic tools. Here, we developed a novel versatile genetic toolbox for rapid and efficient genetic insertion and allelic exchange applicable to P. copri strains from multiple clades. Enabled by the genetic platform, we systematically investigated the specificity of polysaccharide utilization loci (PULs) and identified four highly conserved PULs for utilizing arabinan, pectic galactan, arabinoxylan, and inulin, respectively. Further genetic and functional analysis of arabinan utilization systems illustrate that P. copri has evolved two distinct types of arabinan-processing PULs (PULAra ) and that the type-II PULAra is significantly enriched in individuals consuming a vegan diet compared to other diets. In summary, this genetic toolbox will enable functional genetic studies for P. copri in future.


Assuntos
Dieta Vegetariana , Microbioma Gastrointestinal , Loci Gênicos , Genoma Bacteriano , Polissacarídeos/metabolismo , Prevotella/genética , Prevotella/metabolismo , Fezes/microbiologia , Humanos , Prevotella/classificação , Prevotella/isolamento & purificação
5.
J Infect Dis ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573164

RESUMO

Dysbiosis of the vaginal microbiome poses a serious risk for sexual HIV-1 transmission. Prevotella spp. are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished Prevotella timonensis-enhanced infection. Hence, our study shows that the vaginal microbiome directly affects mucosal CD4+ T cell susceptibility, emphasising importance of vaginal dysbiosis diagnosis and treatment.

6.
BMC Genomics ; 25(1): 495, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769483

RESUMO

Bacteria of the genera Xylanibacter and Segatella are among the most dominant groups in the rumen microbiota. They are characterized by the ability to utilize different hemicelluloses and pectin of plant cell-wall as well as plant energy storage polysaccharides. The degradation is possible with the use of cell envelope bound multiprotein apparatuses coded in polysaccharide utilization loci (PULs), which have been shown to be substrate specific. The knowledge of PUL presence in rumen Xylanibacter and Segatella based on bioinformatic analyses is already established and transcriptomic and genetic approaches confirmed predicted PULs for a limited number of substrates. In this study, we transcriptomically identified additional different PULs in Xylanibacter ruminicola KHP1 and Segatella bryantii TF1-3. We also identified substrate preferences and found that specific growth rate and extent of growth impacted the choice of substrates preferentially used for degradation. These preferred substrates were used by both strains simultaneously as judged by their PUL upregulation. Lastly, ß-glucan and xyloglucan were used by these strains in the absence of bioinformatically and transcriptomically identifiable PUL systems.


Assuntos
Perfilação da Expressão Gênica , Polissacarídeos , Rúmen , Xilanos , Animais , Xilanos/metabolismo , Polissacarídeos/metabolismo , Rúmen/microbiologia , Rúmen/metabolismo , Glucanos/metabolismo , beta-Glucanas/metabolismo , Especificidade por Substrato , Bacteroidetes/genética , Bacteroidetes/metabolismo , Transcriptoma
7.
Cancer Sci ; 115(4): 1141-1153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287724

RESUMO

The indigenous microbial milieu within tumorous tissues exerts a pivotal influence on the genesis and advancement of gastric cancer (GC). This investigation scrutinizes the functions and molecular mechanisms attributed to Prevotella intermedia in the malignant evolution of GC. Isolation of P. intermedia from paired GC tissues was undertaken. Quantification of P. intermedia abundance in 102 tissues was accomplished using quantitative real-time PCR (qRT-PCR). Assessment of the biological effects of P. intermedia on GC cells was observed using culture medium supernatant. Furthermore, the protein profile of GC cells treated with tumor-derived P. intermedia was examined through label-free protein analysis. The functionality of perilipin 3 (PLIN3) was subsequently confirmed using shRNA. Our investigation revealed that the relative abundance of P. intermedia in tumor tissues significantly surpassed that of corresponding healthy tissues. The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042). The supernatant derived from tumor-associated P. intermedia bolstered the proliferation, clone formation, migration, and invasion of GC cells. After indirect co-cultivation with tumor-derived P. intermedia, dysregulation of 34 proteins, including PLIN3, was discerned in GC cells. Knockdown of PLIN3 mitigated the malignancy instigated by P. intermedia in GC cells. Our findings posit that P. intermedia from the tumor microenvironment plays a substantial role in the malignant progression of GC via the modulation of PLIN3 expression. Moreover, the relative abundance of P. intermedia might serve as a potential biomarker for the diagnosis and prognosis of GC.


Assuntos
Neoplasias Gástricas , Humanos , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Perilipina-3 , Prevotella intermedia , Prognóstico , Neoplasias Gástricas/patologia , Microambiente Tumoral
8.
J Neuroinflammation ; 21(1): 147, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835057

RESUMO

BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Animais , Camundongos , Masculino , Reabilitação Neurológica/métodos , Prevotella , Microbioma Gastrointestinal/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo
9.
BMC Infect Dis ; 24(1): 487, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734601

RESUMO

BACKGROUND: A Bartholin's gland abscess is one of the most common infections in women of reproductive age. Although Bartholin's gland abscesses have been reported in prepubertal children, they are rarer in prepubertal children than in adults. Herein, we report a case of bilateral Bartholin's gland abscesses in a 4-year-old girl with vitamin A deficiency. CASE PRESENTATION: A 4-year-old girl diagnosed with autism spectrum disorder was admitted to the hospital for close examination and treatment because of persistent fever and malaise. The child was a marked fussy eater and was diagnosed with corneal ulceration and night blindness secondary to vitamin A deficiency. Both of the patient's labia were swollen, and a diagnosis of a bilateral Bartholin's gland abscess was made using computed tomography. Incisional drainage was performed under general anesthesia. The patient's postoperative course was uneventful, and she was discharged from the hospital on day 8 after the surgery. During hospitalization, attempts were made to correct the vitamin deficiency by adding nutritional supplements to the diet. Three months after the surgery, no recurrence of abscesses was noted. CONCLUSIONS: Decreased immunocompetence and mucosal barrier function due to vitamin A deficiency is thought to be the underlying cause of Bartholin's gland abscesses. Although prepubertal Bartholin's gland abscesses have been reported, they are rare. To the best of our knowledge, no reports of bilateral Bartholin's gland abscesses potentially caused by vitamin A deficiency have been reported. When prepubertal girls present with Bartholin's gland abscesses, the presence of immunodeficiency due to vitamin or trace element deficiency should also be considered.


Assuntos
Abscesso , Glândulas Vestibulares Maiores , Deficiência de Vitamina A , Humanos , Feminino , Pré-Escolar , Abscesso/etiologia , Glândulas Vestibulares Maiores/patologia , Deficiência de Vitamina A/complicações , Tomografia Computadorizada por Raios X , Doenças da Vulva/microbiologia , Doenças da Vulva/cirurgia , Doenças da Vulva/patologia , Doenças da Vulva/etiologia
10.
Dig Dis Sci ; 69(4): 1336-1344, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38446309

RESUMO

BACKGROUND: Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS. AIMS: The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference. METHODS: This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16 S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9. RESULTS: There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS. CONCLUSIONS: There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. ( www. CLINICALTRIALS: gov : NCT04236843).


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Duodeno , Transplante de Microbiota Fecal , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/diagnóstico , Resultado do Tratamento
11.
Oral Dis ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720551

RESUMO

OBJECTIVE: Our previous studies have found that the composition ratio of Prevotella melaninogenica (Pm) on buccal mucosa surface of oral lichen planus (OLP) patients increased significantly compared with control. Furthermore, Pm could invade the epithelium of OLP patients. This study aimed to further explore the impact of Pm on oral keratinocytes. MATERIALS AND METHODS: The Pm-human oral keratinocyte (HOK) co-culture model was established to detect monolayer permeability, zona occludens-1 (ZO-1) expression, and intracellular survival of Pm. We performed RNA-seq followed by identification of differentially expressed genes (DEGs) and Gene Ontology (GO) analysis, with a particular focus on myosin light chain kinase (MLCK). An MLCK inhibitor ML-7 was utilized in Pm-HOK co-culture model to assess its effects on monolayer permeability and ZO-1 expression. RESULTS: HOK monolayer permeability was increased, and ZO-1 expression was decreased after co-culture (p < 0.05). Pm could survive in HOK cells. RNA-seq revealed MLCK was an upregulated common DEG. The expression of MLCK in the Pm-HOK co-culture model was upregulated. Inhibition of MLCK rescued the increased epithelial permeability, and ZO-1 expression was upregulated (p < 0.05). CONCLUSION: MLCK may be involved in disrupting epithelial barrier function by Pm.

12.
Acta Microbiol Immunol Hung ; 71(2): 182-189, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38941152

RESUMO

The aim of this prospective pilot study was to compare culture and microbiome results of the removed tonsils of patients with assumed distant focal disease (11 patients) and those who underwent a tonsillectomy, due to other reasons, such as recurrent tonsillitis, tonsil stones or snoring (nine patients). Aerobic culture was carried out for samples taken from the surface of the tonsils by swabs before tonsillectomy for all 20 patients. The squeezed detritus and the tissue samples of removed tonsils, taken separately for the right and left tonsils, were incubated aerobically and anaerobically. The microbiome composition of tissue samples of removed tonsils was also evaluated. Based on the culture results of the deep samples Staphylococcus aureus was the dominating pathogen, besides a great variety of anaerobic and facultative anaerobic bacteria present in the oral microbiota in those patients who underwent tonsillectomy due to distant focal diseases. Microbiome study of the core tissue samples showed a great diversity on genus and species level among patients of the two groups however, S. aureus and Prevotella nigrescens were present in higher proportion in those, whose tonsils were removed due to distant focal diseases. Our results may support previous findings about the possible triggering role of S. aureus and P. nigrescens leading to distant focal diseases. Samples taken by squeezing the tonsils could give more information about the possible pathogenic/triggering bacteria than the surface samples cultured only aerobically.


Assuntos
Microbiota , Tonsila Palatina , Tonsilectomia , Tonsilite , Humanos , Projetos Piloto , Tonsila Palatina/microbiologia , Estudos Prospectivos , Masculino , Feminino , Adulto , Tonsilite/microbiologia , Tonsilite/cirurgia , Criança , Adolescente , Adulto Jovem , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Staphylococcus aureus/isolamento & purificação , Pessoa de Meia-Idade
13.
Eur Child Adolesc Psychiatry ; 33(3): 847-860, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37071196

RESUMO

Relations between the gut microbiota and host mental health have been suggested by a growing number of case-control and cross-sectional studies, while supporting evidence is limited in large community samples followed during an extended period. Therefore, the current preregistered study ( https://osf.io/8ymav , September 7, 2022) described child gut microbiota development in the first 14 years of life and explored its relations to internalizing and externalizing difficulties and social anxiety in puberty, a period of high relevance for the development of mental health problems. Fecal microbiota composition was analysed by 16S ribosomal RNA gene amplicon sequencing in a total of 1003 samples from 193 children. Through a clustering method, four distinct microbial clusters were newly identified in puberty. Most children within three of these clusters remained in the same clusters from the age of 12 to 14 years, suggesting stability in microbial development and transition during this period. These three clusters were compositionally similar to enterotypes (i.e., a robust classification of the gut microbiota based on its composition across different populations) enriched in Bacteroides, Prevotella, and Ruminococcus, respectively. Two Prevotella 9-predominated clusters, including one reported by us earlier in middle childhood and the other one in puberty, were associated with more externalizing behavior at age 14. One Faecalibacterium-depleted pubertal cluster was related to more social anxiety at age 14. This finding was confirmed by a negative cross-sectional relation between Faecalibacterium and social anxiety in the 14-year-olds. The findings of this study continue to map gut microbiota development in a relatively large community sample followed from birth onwards, importantly extending our knowledge to puberty. Results indicate that Prevotella 9 and Faecalibacterium may be relevant microbial taxa in relation to externalizing behavior and social anxiety, respectively. These correlational findings need validations from other similar cohort studies, as well as well-designed mechanistic pre-clinical investigations before inferring cause and effect.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Criança , Adolescente , Estudos Transversais , Puberdade , Ansiedade
14.
J Oral Rehabil ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850071

RESUMO

BACKGROUND: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified. OBJECTIVE: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults. METHODS: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis. RESULTS: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576). CONCLUSION: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline.

15.
Inflammopharmacology ; 32(1): 561-573, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37921960

RESUMO

Nitro-conjugated linoleic acid (NO2-CLA) has been observed to manifest salutary signaling responses, including anti-inflammatory and antioxidant properties. Here, the authors have explored the influence and underlying mechanisms of NO2-CLA on the proinflammatory reaction of murine macrophages that were challenged with lipopolysaccharide (LPS) derived from Prevotella intermedia, a putative periodontopathic bacterium. Treatment of LPS-activated RAW264.7 cells with NO2-CLA notably dampened the secretion of iNOS-derived NO, IL-1ß and IL-6 as well as their gene expressions and significantly enhanced the markers for M2 macrophage polarization. NO2-CLA promoted the HO-1 expression in cells challenged with LPS, and tin protoporphyrin IX, an HO-1 inhibitor, significantly reversed the NO2-CLA-mediated attenuation of NO secretion, but not IL-1ß or IL-6. We found that cells treated with NO2-CLA significantly increased mRNA expression of PPAR-γ compared to control cells, and NO2-CLA significantly reverted the decrease in PPAR-γ mRNA caused by LPS. Nonetheless, antagonists to PPAR-γ were unable to reverse the NO2-CLA-mediated suppression of inflammatory mediators. In addition, NO2-CLA did not alter the p38 and JNK activation elicited by LPS. Both NF-κB reporter activity and IκB-α degradation caused by LPS were notably diminished by NO2-CLA. NO2-CLA was observed to interrupt the nuclear translocation and DNA binding of p50 subunits caused by LPS with no obvious alterations in p65 subunits. Further, NO2-CLA attenuated the phosphorylation of STAT1/3 elicited in response to LPS. We propose that NO2-CLA could be considered as a possible strategy for the therapy of periodontal disease, although additional researches are certainly required to confirm this.


Assuntos
Ácidos Linoleicos Conjugados , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Prevotella intermedia/química , Interleucina-6/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , Ácidos Linoleicos Conjugados/metabolismo , Dióxido de Nitrogênio/metabolismo , Dióxido de Nitrogênio/farmacologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Macrófagos , RNA Mensageiro/metabolismo
16.
J Infect Dis ; 228(5): 646-656, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37427495

RESUMO

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal dysbiosis that often recurs following first-line antibiotics. We investigated if vaginal microbiota composition was associated with BV recurrence. METHODS: We analyzed samples and data from 121 women who participated in 3 published trials evaluating novel interventions for improving BV cure, including concurrent antibiotic treatment of regular sexual partners (RSPs). Women diagnosed with BV received first-line antibiotics and self-collected vaginal swabs pretreatment and the day after finishing antibiotics (immediately posttreatment). 16S rRNA gene sequencing was performed on vaginal samples. Logistic regression explored associations between BV recurrence and features of the vaginal microbiota pre- and posttreatment. RESULTS: Sixteen women (13% [95% confidence interval {CI}, 8%-21%]) experienced BV recurrence within 1 month of treatment. Women with an untreated RSP were more likely to experience recurrence than women with no RSP (P = .008) or an RSP who received treatment (P = .011). A higher abundance of Prevotella pretreatment (adjusted odds ratio [AOR], 1.35 [95% CI, 1.05-1.91]) and Gardnerella immediately posttreatment (AOR, 1.23 [95% CI, 1.03-1.49]) were associated with increased odds of BV recurrence. CONCLUSIONS: Having specific Prevotella spp prior to recommended treatment and persistence of Gardnerella immediately posttreatment may contribute to the high rates of BV recurrence. Interventions that target these taxa are likely required to achieve sustained BV cure.


Assuntos
Vaginose Bacteriana , Feminino , Humanos , Vaginose Bacteriana/complicações , Antibacterianos/uso terapêutico , Gardnerella/genética , Prevotella/genética , RNA Ribossômico 16S/genética , Vagina/microbiologia , Falha de Tratamento
17.
Microb Pathog ; 176: 106022, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36739100

RESUMO

OBJECTIVE: This study is an investigation of anaerobic nitrite and fumarate reduction/respiration abilities of two characterised Prevotella species namely Prevotella nigrescens (SS6B) and Prevotella buccae (GS6B) isolated from the periodontal pockets of chronic periodontitis (ChP) patients. METHODS: Isolation and identification of the periodontal bacteria from 20 patients showing clinical symptoms of ChP. Characterisation of anaerobic nitrite and fumarate reduction was done in P. nigrescens (SS6B) and P. buccae (GS6B) using reduction assays, inhibition assays with use of specific inhibitors, growth assays and enzyme activity assays. Degenerate PCR was used to detect and amplify nitrite reductase (nrfA) and fumarate reductase (frdA) gene sequences in these Prevotella isolates. In addition, molecular and in silico analysis of the amplified anaerobic reductase gene sequences was performed using NCBI conserved domain analysis, Interpro database and MegaX. RESULTS: We provided experimental evidence for presence of active nitrite and fumarate reductase activities through enzyme activity, reduction, inhibitor and growth assays. Moreover, we were able to detect presence of 505 bps nrfA gene fragment and 400 bps frdA gene fragment in these Prevotella spp. These fragments show similarity to multiheme ammonia forming cytochrome c nitrite reductases and fumarate reductases flavoprotein subunit, respectively. CONCLUSION: Anaerobic nitrite and fumarate respiration abilities in P. nigrescens and P. buccae isolates appear to be important for detoxification process and growth, respectively.


Assuntos
Periodontite Crônica , Humanos , Prevotella nigrescens/genética , Prevotella nigrescens/metabolismo , Nitritos , Succinato Desidrogenase
18.
Arch Microbiol ; 206(1): 32, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127130

RESUMO

Members of the family Prevotellaceae are Gram-negative, obligate anaerobic bacteria found in animal and human microbiota. In Prevotella bryantii, the Na+-translocating NADH:quinone oxidoreductase (NQR) and quinol:fumarate reductase (QFR) interact using menaquinone as electron carrier, catalyzing NADH:fumarate oxidoreduction. P. bryantii NQR establishes a sodium-motive force, whereas P. bryantii QFR does not contribute to membrane energization. To elucidate the possible mode of function, we present 3D structural models of NQR and QFR from P. bryantii to predict cofactor-binding sites, electron transfer routes and interaction with substrates. Molecular docking reveals the proposed mode of menaquinone binding to the quinone site of subunit NqrB of P. bryantii NQR. A comparison of the 3D model of P. bryantii QFR with experimentally determined structures suggests alternative pathways for transmembrane proton transport in this type of QFR. Our findings are relevant for NADH-dependent succinate formation in anaerobic bacteria which operate both NQR and QFR.


Assuntos
Hidroquinonas , NAD , Animais , Humanos , Succinato Desidrogenase , Simulação de Acoplamento Molecular , Vitamina K 2 , Íons , Sódio
19.
BMC Neurol ; 23(1): 383, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872501

RESUMO

BACKGROUND: Isolated Prevotella intermedia, a rare gram-negative, rod-shaped, anaerobic bacterium, is rarely detected in clinical practice. It has been associated with infections of the oral cavity and female genital tract, but has never been detected in cerebrospinal fluid (CSF) of patients in China. Accurate detection of causative pathogens is still an arduous task owing to the difficult conditions of anaerobic bacterial culture. Isolated Prevotella intermedia can be detected by metagenomic next generation sequencing (mNGS) of the CSF. Correct diagnosis and antibiotic treatment can help patients avoid life-threatening events. CASE PRESENTATION: Herein, we describe the case of a 64-year-old Chinese woman who presented with typical features of meningoencephalitis. Routine CSF culture failed to identify the causative pathogen. Isolated Prevotella intermedia was detected by mNGS, and the patient was treated with antibacterial agents including ceftriaxone, vancomycin, moxifloxacin, meropenem, metronidazole, and linezolid. The patient underwent surgical treatment for abscess of left frontal parietal lobe, which was observed on magnetic resonance imaging (MRI) and was suspected to be caused by Prevotella intermedia. It was further confirmed that it was a secondary infection from the oral cavity, and the possible etiology might have been dental surgery. Treatment was rendered to the patient based on metagenomic test result, and her condition improved after two months. CONCLUSIONS: This case highlights the role of mNGS in accurate diagnosis of patients with central nervous system infection. In particular, mNGS can be used to identify rare pathogens and confirm the diagnosis in patients with unknown etiology.


Assuntos
Antibacterianos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Feminino , Pessoa de Meia-Idade , Composição de Bases , Filogenia , Prevotella intermedia/genética , RNA Ribossômico 16S , Análise de Sequência de DNA , Antibacterianos/uso terapêutico
20.
BMC Infect Dis ; 23(1): 633, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37759232

RESUMO

BACKGROUND: Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well. CONCLUSION: We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.


Assuntos
Abscesso Encefálico , Masculino , Humanos , Pessoa de Meia-Idade , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/tratamento farmacológico , Prevotella/genética , Encéfalo/diagnóstico por imagem , Terapia Combinada
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