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1.
Arch Virol ; 169(10): 196, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256248

RESUMO

Vibrio parahaemolyticus is a major seafood-borne zoonotic pathogen that causes gastroenteritis in humans and acute hepatopancreatic necrosis disease (AHPND) in shrimp. In this study, we isolated and characterized Vibrio phage vB_VpM-pA2SJ1, which infects clinical and AHPND-associated strains of V. parahaemolyticus. The phage genome is a linear dsDNA 51,054 bp in length with a G + C content of 43.7%, and it contains 89 open reading frames. Genome comparisons revealed basal similarity to other Vibrio phages, particularly Vibrio phage vB_VpP_1, with 84.2% identity and 46% coverage. Phylogenetic analysis based on the whole genome, the terminase large subunit, and the major capsid protein revealed that phage vB_VpM-pA2SJ1 did not cluster with other known phage families, thus indicating its uniqueness.


Assuntos
Bacteriófagos , Composição de Bases , Genoma Viral , Fases de Leitura Aberta , Filogenia , Vibrio parahaemolyticus , Vibrio parahaemolyticus/virologia , Vibrio parahaemolyticus/genética , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/classificação , Animais , Penaeidae/virologia , Penaeidae/microbiologia , Vibrioses/microbiologia , Vibrioses/virologia , Vibrioses/veterinária , Hepatopâncreas/virologia , Hepatopâncreas/microbiologia , Hepatopâncreas/patologia , DNA Viral/genética
2.
NPJ Biofilms Microbiomes ; 10(1): 50, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902263

RESUMO

During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as 'maskne' (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either 'pathogen helper (PH)' or 'pathogen inhibitor (PIn)' strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.


Assuntos
COVID-19 , Máscaras , Microbiota , Pele , Animais , Camundongos , Humanos , COVID-19/microbiologia , COVID-19/virologia , Pele/microbiologia , Acne Vulgar/microbiologia , SARS-CoV-2 , Feminino , Metagenômica/métodos , Modelos Animais de Doenças , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Interações Microbianas , Dermatite de Contato/etiologia
3.
ACS Nano ; 18(25): 16297-16311, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38867457

RESUMO

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.


Assuntos
Doenças Inflamatórias Intestinais , Macrófagos , Mesalamina , Pró-Fármacos , Mesalamina/química , Mesalamina/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Camundongos , Humanos , Nanopartículas/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem
4.
Int J Antimicrob Agents ; 64(1): 107187, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38697577

RESUMO

Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2'-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2'-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection.


Assuntos
Trissacarídeos , Animais , Camundongos , Humanos , Trissacarídeos/farmacologia , Trissacarídeos/imunologia , Células A549 , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Feminino , SARS-CoV-2/imunologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , COVID-19/imunologia , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Suplementos Nutricionais , Óxido Nítrico/metabolismo , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Pulmão/imunologia , Pulmão/virologia , Oligossacarídeos
5.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732060

RESUMO

The human gut microbiota, an intricate ecosystem within the gastrointestinal tract, plays a pivotal role in health and disease. Prebiotics, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of beneficial microorganisms, have emerged as a key modulator of this complex microbial community. This review article explores the evolution of the prebiotic concept, delineates various types of prebiotics, including fructans, galactooligosaccharides, xylooligosaccharides, chitooligosaccharides, lactulose, resistant starch, and polyphenols, and elucidates their impact on the gut microbiota composition. We delve into the mechanisms through which prebiotics exert their effects, particularly focusing on producing short-chain fatty acids and modulating the gut microbiota towards a health-promoting composition. The implications of prebiotics on human health are extensively reviewed, focusing on conditions such as obesity, inflammatory bowel disease, immune function, and mental health. The review further discusses the emerging concept of synbiotics-combinations of prebiotics and probiotics that synergistically enhance gut health-and highlights the market potential of prebiotics in response to a growing demand for functional foods. By consolidating current knowledge and identifying areas for future research, this review aims to enhance understanding of prebiotics' role in health and disease, underscoring their importance in maintaining a healthy gut microbiome and overall well-being.


Assuntos
Microbioma Gastrointestinal , Prebióticos , Humanos , Probióticos/farmacologia , Obesidade/microbiologia , Obesidade/dietoterapia , Obesidade/metabolismo , Ácidos Graxos Voláteis/metabolismo , Animais , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/dietoterapia
6.
Biomedicines ; 12(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38672155

RESUMO

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

7.
Ther Adv Neurol Disord ; 17: 17562864231218181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250318

RESUMO

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

8.
Front Nutr ; 10: 1249358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024360

RESUMO

Introduction: Green banana flour can be used as a prebiotic due to its ability to promote gut health and provide several health benefits. In this study, we investigated whether feeding mice green banana flour at different doses would alter intestinal microbiota composition. Methods: We fed C57BL/6N mice either a Low-dose (500 mg/kg/day) or High-dose (2000 mg/kg/day) of green banana flour daily for 3 weeks, and fecal samples were collected on days 0, 14, and 21 for microbiota analysis. Results: Our results showed that the composition of intestinal microbiota was significantly altered by day 21, regardless of the dose. Notably, the consumption of green banana flour increased the presence of beneficial bacteria, including Coriobacteriaceae_UCG-002, Turicibacter, Parasutterella, Gastranaerophilales_ge, and RF39_ge. These changes in the intestinal microorganisms were accompanied by increased biological processes such as amino acid biosynthesis and secondary metabolite biosynthesis. Conversely, the consumption of green banana flour resulted in a decrease in biological processes related to carbohydrate degradation, glycerol degradation, and similar functions. Discussion: These results emphasize the potential of green banana flour as a prebiotic that can benefit the gut microbiome.

9.
Viruses ; 15(9)2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37766351

RESUMO

Since its initial report in Vietnam in early 2019, the African swine fever (ASF), a highly lethal and severe viral swine disease worldwide, continues to cause outbreaks in other Southeast Asian countries. This study analyzed and compared the genomic sequences of ASF viruses (ASFVs) during the first outbreak in Hung Yen (VN/HY/2019-ASFV1) and Quynh Phu provinces (VN/QP/2019-ASFV1) in Vietnam in 2019, and the subsequent outbreak in Hung Yen (VN/HY/2022-ASFV2) in 2022, to those of other ASFV strains. VN/HY/2019-ASFV1, VN/QP/2019-ASFV1, and VN/HY/2022-ASFV2 genomes were 189,113, 189,081, and 189,607 bp in length, encoding 196, 196, and 203 open reading frames (ORFs), respectively. VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 shared a 99.91-99.99% average nucleotide identity with genotype II strains. Variations were identified in 28 ORFs in VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 compared to 20 ASFV strains, and 16 ORFs in VN/HY/2022-ASFV2 compared to VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1. Vietnamese ASFV genomes were classified as IGR II variants between the I73R and I329L genes, with two copy tandem repeats between the A179L and A137R genes. A phylogenetic analysis based on the whole genomes of 27 ASFV strains indicated that the Vietnamese ASFV strains are genetically related to Estonia 2014, ASFV-SY18, and Russia/Odintsovo_02/14. These results reveal the complete genome sequences of ASFV circulating during the first outbreak in 2019, providing important insights into understanding the evolution, transmission, and genetic variation of ASFV in Vietnam.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Animais , Suínos , Vírus da Febre Suína Africana/genética , Vietnã/epidemiologia , Febre Suína Africana/epidemiologia , Filogenia , Surtos de Doenças
10.
Microbiol Spectr ; 11(4): e0278022, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37358445

RESUMO

Microbes found in the digestive tracts of insects are known to play an important role in their host's behavior. Although Lepidoptera is one of the most varied insect orders, the link between microbial symbiosis and host development is still poorly understood. In particular, little is known about the role of gut bacteria in metamorphosis. Here, we explored gut microbial biodiversity throughout the life cycle of Galleria mellonella, using amplicon pyrosequencing with the V1 to V3 regions, and found that Enterococcus spp. were abundant in larvae, while Enterobacter spp. were predominant in pupae. Interestingly, eradication of Enterococcus spp. from the digestive system accelerated the larval-to-pupal transition. Furthermore, host transcriptome analysis demonstrated that immune response genes were upregulated in pupae, whereas hormone genes were upregulated in larvae. In particular, regulation of antimicrobial peptide production in the host gut correlated with developmental stage. Certain antimicrobial peptides inhibited the growth of Enterococcus innesii, a dominant bacterial species in the gut of G. mellonella larvae. Our study highlights the importance of gut microbiota dynamics on metamorphosis as a consequence of the active secretion of antimicrobial peptides in the G. mellonella gut. IMPORTANCE First, we demonstrated that the presence of Enterococcus spp. is a driving force for insect metamorphosis. RNA sequencing and peptide production subsequently revealed that antimicrobial peptides targeted against microorganisms in the gut of Galleria mellonella (wax moth) did not kill Enterobacteria species, but did kill Enterococcus species, when the moth was at a certain stage of growth, and this promoted moth pupation.


Assuntos
Enterococcus , Mariposas , Animais , Enterococcus/genética , Mariposas/microbiologia , Larva/microbiologia , Insetos , Bactérias , Peptídeos Antimicrobianos , Dinâmica Populacional
11.
Nutrients ; 15(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37299573

RESUMO

Alterations in the intestinal microbial flora are known to cause various diseases, and many people routinely consume probiotics or prebiotics to balance intestinal microorganisms and the growth of beneficial bacteria. In this study, we selected a peptide from fish (tilapia) skin that induces significant changes in the intestinal microflora of mice and reduces the Firmicutes/Bacteroidetes ratio, which is linked to obesity. We attempted to verify the anti-obesity effect of selected fish collagen peptides in a high-fat-diet-based obese mouse model. As anticipated, the collagen peptide co-administered with a high-fat diet significantly inhibited the increase in the Firmicutes/Bacteroidetes ratio. It increased specific bacterial taxa, including Clostridium_sensu_stricto_1, Faecalibaculum, Bacteroides, and Streptococcus, known for their anti-obesity effects. Consequently, alterations in the gut microbiota resulted in the activation of metabolic pathways, such as polysaccharide degradation and essential amino acid synthesis, which are associated with obesity inhibition. In addition, collagen peptide also effectively reduced all obesity signs caused by a high-fat diet, such as abdominal fat accumulation, high blood glucose levels, and weight gain. Ingestion of collagen peptides derived from fish skin induced significant changes in the intestinal microflora and is a potential auxiliary therapeutic agent to suppress the onset of obesity.


Assuntos
Bacteroidetes , Firmicutes , Animais , Camundongos , Obesidade/metabolismo , Aumento de Peso , Bactérias , Dieta Hiperlipídica , Peptídeos/farmacologia , Camundongos Endogâmicos C57BL
12.
J Antimicrob Chemother ; 78(4): 923-932, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36880170

RESUMO

BACKGROUND: Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect. OBJECTIVES: To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance. METHODS: By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms. RESULTS: PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs. CONCLUSIONS: Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance.


Assuntos
Acinetobacter baumannii , Polimixina B , Animais , Camundongos , Polimixina B/farmacologia , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Polimixinas/farmacologia , Testes de Sensibilidade Microbiana
14.
IEEE Trans Nanobioscience ; 22(3): 622-629, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36399595

RESUMO

This paper studies a novel electrophoretic molecular communication (EMC) framework utilizing a piecewise constant electric field. EMC is a particular type of molecular communication that exploits electric fields to induce the movement of charged particles to enhance communication performance. Our previous work proposed an EMC framework utilizing a time-varying electric field that exponentially changes; however, the field with such a complicated shape might be challenging to be implemented in practice. Thus, this paper proposes a new EMC approach exploiting a piecewise constant electric field that can be readily implemented via, e.g., an on/off switch method. We formulate two optimization problems to design the electric field based on different objectives: minimizing a mean squared error and minimizing a bit interval. The solutions of each, such as optimal on-off timings and corresponding strengths of the constant electric fields, are obtained through the Lagrange multiplier approach and the geometric programming, respectively. The Monte Carlo simulation results verify that the proposed piecewise constant electric field significantly reduces the bit error rate relative to the constant field benchmark while performing less well, but not significantly, than the exponential field benchmark.


Assuntos
Comunicação , Eletroforese , Simulação por Computador
15.
Aging (Albany NY) ; 14(16): 6449-6466, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35980280

RESUMO

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline. The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment. Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: 16.00, median, 13.00-18.00 [IQR] vs. 10.0, median, 9.8-15.3 [IQR]); CDR-SB: 5.50, median, 4.00-8.00 [IQR]) vs. 8.0, median, 7.9-12.5, [IQR]). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT. This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Disfunção Cognitiva , Demência , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções por Clostridium/complicações , Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Cognição , Disfunção Cognitiva/terapia , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Humanos , Resultado do Tratamento
16.
Medicine (Baltimore) ; 101(12): e29135, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35357354

RESUMO

RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established. PATIENT CONCERNS AND DIAGNOSIS: We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection. INTERVENTIONS: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT. OUTCOMES: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS. LESSONS: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.


Assuntos
Transplante de Microbiota Fecal , Polipose Intestinal , Idoso , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Humanos , Polipose Intestinal/terapia , Masculino , RNA Ribossômico 16S/genética , Esteroides
17.
EMBO Mol Med ; 14(1): e14678, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34842355

RESUMO

Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three-dimensional (3D)-cultured spheroids or organoids mimicking the human kidney. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.


Assuntos
Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Animais , Estresse do Retículo Endoplasmático , Síndrome Hemolítico-Urêmica/patologia , Rim/patologia , Camundongos , Toxina Shiga/metabolismo , Toxinas Shiga
18.
Environ Microbiol ; 23(11): 7245-7254, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34668292

RESUMO

Cryptic prophages are not genomic junk but instead enable cells to combat myriad stresses as an active stress response. How these phage fossils affect persister cell resuscitation has, however, not been explored. Persister cells form as a result of stresses such as starvation, antibiotics and oxidative conditions, and resuscitation of these persister cells likely causes recurring infections such as those associated with tuberculosis, cystic fibrosis and Lyme disease. Deletion of each of the nine Escherichia coli cryptic prophages has no effect on persister cell formation. Strikingly, elimination of each cryptic prophage results in an increase in persister cell resuscitation with a dramatic increase in resuscitation upon deleting all nine prophages. This increased resuscitation includes eliminating the need for a carbon source and is due to activation of the phosphate import system resulting from inactivating the transcriptional regulator AlpA of the CP4-57 cryptic prophage. Deletion of alpA increases persister resuscitation, and AlpA represses phosphate regulator PhoR. Both phosphate regulators PhoP and PhoB stimulate resuscitation. This suggests a novel cellular stress mechanism controlled by cryptic prophages: regulation of phosphate uptake which controls the exit of the cell from dormancy and prevents premature resuscitation in the absence of nutrients.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Humanos , Nutrientes , Prófagos/genética
19.
Curr Med Res Opin ; 37(10): 1739-1744, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34289768

RESUMO

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia.


Assuntos
Doença de Alzheimer , Clostridioides difficile , Infecções por Clostridium , Idoso de 80 Anos ou mais , Doença de Alzheimer/terapia , Infecções por Clostridium/terapia , Cognição , Transplante de Microbiota Fecal , Fezes , Feminino , Humanos , RNA Ribossômico 16S/genética , Resultado do Tratamento
20.
Comput Struct Biotechnol J ; 18: 2494-2500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005311

RESUMO

Archaea are members of most microbiomes. While archaea are highly abundant in extreme environments, they are less abundant and diverse in association with eukaryotic hosts. Nevertheless, archaea are a substantial constituent of plant-associated ecosystems in the aboveground and belowground phytobiome. Only a few studies have investigated the role of archaea in plant health and its potential symbiosis in ecosystems. This review discusses recent progress in identifying how archaea contribute to plant traits such as growth, adaptation to abiotic stresses, and immune activation. We synthesized the most recent functional and molecular data on archaea, including root colonization and the volatile emission to activate plant systemic immunity. These data represent a paradigm shift in our understanding of plant-microbiota interactions.

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