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1.
J Biol Chem ; 300(3): 105675, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272223

RESUMO

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1-2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.


Assuntos
Colo , Fezes , Proteômica , Animais , Humanos , Camundongos , Colo/metabolismo , Glicoproteínas/metabolismo , Mucosa Intestinal/metabolismo , Mucina-2/genética , Mucina-2/metabolismo , Muco/metabolismo , Suínos , Masculino , Camundongos Endogâmicos C57BL , Microbioma Gastrointestinal
2.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809421

RESUMO

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.


Assuntos
COVID-19/epidemiologia , Transplante de Microbiota Fecal/métodos , Pandemias , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Humanos , Pulmão/fisiopatologia , Resultado do Tratamento
3.
Microb Biotechnol ; 17(10): e70030, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388360

RESUMO

The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut-brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome-centred interventions for preventing and treating OUD.


Assuntos
Analgésicos Opioides , Microbioma Gastrointestinal , Transtornos Relacionados ao Uso de Opioides , Humanos , Transtornos Relacionados ao Uso de Opioides/terapia , Analgésicos Opioides/uso terapêutico , Eixo Encéfalo-Intestino/fisiologia , Animais , Dor Crônica/microbiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38248533

RESUMO

Adverse childhood experiences (ACEs) encompass negative, stressful, and potentially traumatic events during childhood, impacting physical and mental health outcomes in adulthood. Limited studies suggest ACEs can have short-term effects on children's gut microbiomes and adult cognitive performance under stress. Nevertheless, the long-term effects of ACEs experienced during adulthood remain unexplored. Thus, this study aimed to assess the long-term effects of ACEs on the gut microbiota of adult nursing students. We employed a multidimensional approach, combining 16S rRNA sequencing, bioinformatics tools, and machine learning to predict functional capabilities. High-ACE individuals had an increased abundance of Butyricimonas spp. and Prevotella spp. and decreased levels of Clostridiales, and Lachnospira spp. Prevotella abundance correlated negatively with L-glutamate and L-glutamine biosynthesis, potentially impacting intestinal tissue integrity. While nursing students with high ACE reported increased depression, evidence for a direct gut microbiota-depression relationship was inconclusive. High-ACE individuals also experienced a higher prevalence of diarrhea. These findings highlight the long-lasting impact of ACEs on the gut microbiota and its functions in adulthood, particularly among nursing students. Further research is warranted to develop targeted interventions and strategies for healthcare professionals, optimizing overall health outcomes.


Assuntos
Experiências Adversas da Infância , Microbioma Gastrointestinal , Estudantes de Enfermagem , Adulto , Criança , Humanos , RNA Ribossômico 16S/genética , Biologia Computacional
5.
ACS Nano ; 17(14): 13393-13407, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37417775

RESUMO

Detection of viable viruses in the air is critical in order to determine the level of risk associated with the airborne diffusion of viruses. Different methods have been developed for the isolation, purification, and detection of viable airborne viruses, but they require an extensive processing time and often present limitations including low physical efficiency (i.e., the amount of collected viruses), low biological efficiency (i.e., the number of viable viruses), or a combination of all. To mitigate such limitations, we have employed an efficient technique based on the magnetic levitation (Maglev) technique with a paramagnetic solution and successfully identified distinct variations in levitation and density characteristics among bacteria (Escherichia coli), phages (MS2), and human viruses (SARS-CoV-2 and influenza H1N1). Notably, the Maglev approach enabled a significant enrichment of viable airborne viruses in air samples. Furthermore, the enriched viruses obtained through Maglev exhibited high purity, rendering them suitable for direct utilization in subsequent analyses such as reverse transcription-polymerase chain reaction (RT-PCR) or colorimetric assays. The system is portable, easy to use, and cost-efficient and can potentially provide proactive surveillance data for monitoring future outbreaks of airborne infectious diseases and allow for the induction of various preventative and mitigative measures.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vírus , Humanos , SARS-CoV-2 , Fenômenos Magnéticos
6.
Microbiome ; 8(1): 36, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32169105

RESUMO

Coronary artery disease (CAD) is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Over the past decade, it has become clear that the inhabitants of our gut, the gut microbiota, play a vital role in human metabolism, immunity, and reactions to diseases, including CAD. Although correlations have been shown between CAD and the gut microbiota, demonstration of potential causal relationships is much more complex and challenging. In this review, we will discuss the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Uncovering the causal relationship of gut microbiota and CAD development can lead to novel microbiome-based preventative and therapeutic interventions. However, an interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms (e.g., using advanced nanomedicine technologies and incorporation of demographic factors such as age, sex, and ethnicity) to enable efficacious and high-precision preventative and therapeutic strategies for CAD.


Assuntos
Bactérias/metabolismo , Doenças Cardiovasculares/microbiologia , Microbioma Gastrointestinal , Animais , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/terapia , Colesterol/metabolismo , Doença da Artéria Coronariana/microbiologia , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/terapia , Fezes/microbiologia , Humanos
7.
Sci Rep ; 10(1): 18349, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110112

RESUMO

Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.


Assuntos
Transplante de Microbiota Fecal , Fezes/microbiologia , Microbioma Gastrointestinal , Adulto , Bacteroidetes/metabolismo , Clostridiales/metabolismo , Clostridioides/metabolismo , Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Desulfovibrio/metabolismo , Feminino , Microbioma Gastrointestinal/genética , Humanos , Aprendizado de Máquina , Masculino , Metagenômica , Doadores de Tecidos , Resultado do Tratamento
8.
Science ; 370(6515): 467-472, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33093110

RESUMO

Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon-derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.


Assuntos
Colo/metabolismo , Colo/microbiologia , Microbioma Gastrointestinal , Mucina-2/metabolismo , Muco/metabolismo , Animais , Fezes/microbiologia , Glicosilação , Camundongos , Camundongos Knockout , Mucina-2/genética , Transcrição Gênica
9.
PLoS One ; 14(8): e0220556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374095

RESUMO

The new era in the design of modern healthy buildings necessitates multidisciplinary research efforts that link principles of engineering and material sciences with those of building biology, in order to better comprehend and apply underlying interactions among design criteria. As part of this effort, there have been an array of studies in relation to the effects of building characteristics on indoor microbiota and their propensity to cause health issues. Despite the abundance of scientific inquiries, limited studies have been dedicated to concomitantly link these effects to the deterioration of 'structural integrity' in the building materials. This study focuses on the observed biodeteriorative capabilities of indoor fungi upon the ubiquitous gypsum board material as a function of building age and room functionality within a university campus. We observed that the fungal growth significantly affected the physical (weight loss) and mechanical (tensile strength) properties of moisture-exposed gypsum board samples; in some cases, tensile strength and weight decreased by more than 80%. Such intertwined associations between the biodeterioration of building material properties due to viable indoor fungi, and as a function of building characteristics, would suggest a critical need towards multi-criteria design and optimization of next-generation healthy buildings. Next to structural integrity measures, with a better understanding of what factors and environmental conditions trigger fungal growth in built environment materials, we can also optimize the design of indoor living spaces, cleaning strategies, as well as emergency management measures during probable events such as flooding or water damage.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Materiais de Construção/microbiologia , Monitoramento Ambiental , Fungos/crescimento & desenvolvimento , Saúde Ambiental , Universidades
10.
Materials (Basel) ; 10(11)2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29088118

RESUMO

The development and application of bio-sourced composites have been gaining wide attention, yet their deterioration due to the growth of ubiquitous microorganisms during storage/manufacturing/in-service phases is still not fully understood for optimum material selection and design purposes. In this study, samples of non-woven flax fibers, hemp fibers, and mats made of co-mingled randomly-oriented flax or hemp fiber (50%) and polypropylene fiber (50%) were subjected to 28 days of exposure to (i) no water-no fungi, (ii) water only and (iii) water along with the Chaetomium globosum fungus. Biocomposite samples were measured for weight loss over time, to observe the rate of fungal growth and the respiration of cellulose components in the fibers. Tensile testing was conducted to measure mechanical properties of the composite samples under different configurations. Scanning electron microscopy was employed to visualize fungal hyphal growth on the natural fibers, as well as to observe the fracture planes and failure modes of the biocomposite samples. Results showed that fungal growth significantly affects the dry mass as well as the tensile elastic modulus of the tested natural fiber mats and composites, and the effect depends on both the type and the length scale of fibers, as well as the exposure condition and time.

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