RESUMO
Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
Assuntos
Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Disbiose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , CarcinogêneseRESUMO
Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy, resulting in diminished quality of life and potential treatment disruptions. Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM). Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis. Therefore, approaches that modulate oral microbial ecology are promising for the management of RIOM. Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest. In this review, we discussed the correlation between RIOM and oral microbiota, with a particular focus on the efficacy of probiotics in the control of RIOM, in order to provide novel paradigm for the management of this disease.
Assuntos
Disbiose , Probióticos , Lesões por Radiação , Estomatite , Probióticos/uso terapêutico , Humanos , Estomatite/etiologia , Estomatite/microbiologia , Estomatite/terapia , Estomatite/prevenção & controle , Lesões por Radiação/terapia , Microbiota , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia/efeitos adversos , Boca/microbiologia , Qualidade de VidaRESUMO
Background: Recent evidence suggests that the gut microbiome and metabolites are intricately involved in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis, yet the precise causal relationships remain unclear due to confounding factors and reverse causation. This study employs bidirectional two-sample Mendelian Randomization (MR) to clarify these connections. Methods: Summary data from publicly available Genome-Wide Association Studies (GWAS) concerning the gut microbiome, metabolites, and COPD were compiled. The selection of genetic instrumental variables (Single Nucleotide Polymorphisms, or SNPs) for MR analysis was conducted meticulously, primarily utilizing the Inverse Variance Weighting (IVW) method, supplemented by MR-Egger regression and the Weighted Median (WM) approach. The evaluation of heterogeneity and horizontal pleiotropy was performed using Cochran's Q test, the MR-Egger intercept test, and the MR-PRESSO global test. Sensitivity analyses, including leave-one-out tests, were conducted to verify the robustness of our results. And the mediation effect of gut microbiota-mediated changes in metabolites on the causal relationship with COPD was analyzed. Results: Our study identified nine significant gut microbiota taxa and thirteen known metabolites implicated in COPD pathogenesis. Moreover, associations between the onset of COPD and the abundance of five bacterial taxa, as well as the concentration of three known metabolites, were established. These findings consistently withstood sensitivity analyses, reinforcing their credibility. Additionally, our results revealed that gut microbiota contribute to the development of COPD by mediating changes in metabolites. Conclusion: Our bidirectional Two-Sample Mendelian Randomization analysis has revealed reciprocal causal relationships between the abundance of gut microbiota and metabolite concentrations in the context of COPD. This research holds promise for identifying biomarkers for early COPD diagnosis and monitoring disease progression, thereby opening new pathways for prevention and treatment. Further investigation into the underlying mechanisms is essential to improve our understanding of COPD onset.
Assuntos
Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Humanos , Fatores de Risco , Predisposição Genética para Doença , Pulmão/microbiologia , Pulmão/fisiopatologia , Fenótipo , Medição de Risco , Disbiose , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
Objective: The importance of early microbial dysbiosis in later development of obesity and metabolic disorders has been a subject of debate. Here we tested cause and effect in mice. Methods: Germ-free male Swiss Webster mice were colonized in a specific-pathogen-free (SPF) facility at 1 week (1W) and 3 weeks (3W) of age. They were challenged with a high-fat diet and their responses were compared with SPF mice. Gut microbiota was analyzed by 16S rRNA gene sequencing. Moreover, RNA sequencing of the liver was performed on additional 3W and SPF mice on a regular chow diet. Results: There were no significant differences in weight, food consumption, epididymal fat weight, HbA1c levels, and serum insulin and leptin, whereas the early germ-free period resulted in mice with impaired glucose tolerance. Both the 1W and 3W group peaked 56% (p < 0.05) and 66% (p < 0.01) higher in blood glucose than the SPF control group, respectively. This was accompanied by a 45% reduction in the level of the anti-inflammatory cytokine IL-10 in the 1W mice (p < 0.05). There were no differences in the gut microbiota between the groups, indicating that all mice colonized fully after the germ-free period. Marked effects on hepatic gene expression (728 differentially expressed genes with adjusted p < 0.05 and a fold change ± 1.5) suggested a potential predisposition to a higher risk of developing insulin resistance in the 3W group. Conclusions: Lack of microbes early in life had no impact on adiposity but led to insulin resistance and altered liver gene expression related to glucose metabolism in mice. The study strongly supports the notion that microbial signaling to the liver in the beginning of life can alter the host's risk of developing metabolic disorder later in life.
Assuntos
Adiposidade , Microbioma Gastrointestinal , Resistência à Insulina , Fígado , Obesidade , Animais , Camundongos , Masculino , Fígado/metabolismo , Obesidade/microbiologia , Camundongos Obesos , Dieta Hiperlipídica , Disbiose , Expressão GênicaRESUMO
BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner. METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry. RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males. CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.
Assuntos
Colite , Disbiose , Microbioma Gastrointestinal , Dor Visceral , Masculino , Feminino , Animais , Disbiose/microbiologia , Dor Visceral/microbiologia , Dor Visceral/fisiopatologia , Dor Visceral/metabolismo , Colite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Microbiota Fecal , Fatores Sexuais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , RNA Ribossômico 16S/genética , Fezes/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Dor Crônica/microbiologia , Dor Crônica/fisiopatologia , Inflamação/microbiologia , Hiperalgesia/microbiologiaRESUMO
This letter emphasizes the need to expand discussions on gut microbiome's role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) by including the often-overlooked non-bacterial components of the human gut flora. It highlights how viral, fungal and archaeal inhabitants of the gut respond towards gut dys-biosis and contribute to disease progression. Viruses such as bacteriophages target certain bacterial species and modulate the immune system. Other viruses found associated include Epstein-Barr virus, human papillomavirus, John Cunningham virus, cytomegalovirus, and human herpes simplex virus type 6. Fungi such as Candida albicans and Malassezia contribute by forming tissue-invasive filaments and producing inflammatory cytokines, respectively. Archaea, mainly metha-nogens are also found altering the microbial fermentation pathways. This corres-pondence, thus underscores the significance of considering the pathological and physiological mechanisms of the entire spectrum of the gut microbiota to develop effective therapeutic interventions for both IBD and CRC.
Assuntos
Neoplasias Colorretais , Progressão da Doença , Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/imunologia , Disbiose/imunologia , Bactérias , Fungos/imunologia , Fungos/patogenicidadeRESUMO
OBJECTIVES: The dietary composition is able to rapidly and significantly influence the diversity of the gut microbiome. This article focuses on how various types of diet affect the composition of the gut microbiome and how dietary changes are able to prevent or slow down the development of non-communicable diseases including obesity, type 2 diabetes mellitus, cardiovascular diseases, and low-grade inflammation. METHODS: A review in PubMed and a hand search using references in identified articles were performed. Studies published in English from 2000 to 2024 were included. RESULTS: The studies showed the significant effect of diet on the development of non-communicable diseases dependent on the state of the gut microbiota and molecules it produces. The Western diet that continues to gain in popularity for Czech people, leads to dysbiosis and production of bacterial lipopolysaccharide or trimethylamine N-oxide causing systemic chronic inflammation in the body and thus promoting the development of non-communicable diseases. CONCLUSIONS: Findings from this review emphasize the importance of healthy eating habits in the prevention of intestinal dysbiosis and still increasing prevalence and incidence of obesity and other non-communicable diseases.
Assuntos
Dieta , Microbioma Gastrointestinal , Doenças não Transmissíveis , Humanos , Microbioma Gastrointestinal/fisiologia , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Obesidade/microbiologia , Obesidade/epidemiologia , Disbiose , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/epidemiologia , República Tcheca/epidemiologia , InflamaçãoRESUMO
Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.
Assuntos
Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal , Fator 1 Induzível por Hipóxia , Mucosa Intestinal , Transdução de Sinais , Vitamina B 12 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina B 12/farmacologia , Vitamina B 12/metabolismo , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Transdução de Sinais/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Fator 1 Induzível por Hipóxia/metabolismo , Colite/metabolismo , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Colite/tratamento farmacológico , Disbiose/microbiologia , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Drosophila/metabolismoRESUMO
The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.
Assuntos
Asma , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Prebióticos , Probióticos , Humanos , Probióticos/uso terapêutico , Asma/microbiologia , Asma/imunologia , Asma/terapia , Animais , Pulmão/microbiologia , Pulmão/imunologia , Pulmão/metabolismo , Pneumopatias/microbiologia , Pneumopatias/terapia , Pneumopatias/imunologiaRESUMO
Recent years have seen an outstanding growth in the understanding of connections between diet-induced obesity, dysbiosis and alterations in the tumor microenvironment. Now we appreciate that gut dysbiosis can exert important effects in distant target tissues via specific microbes and metabolites. Multiple studies have examined how diet-induced obese state is associated with gut dysbiosis and how gut microbes direct various physiological processes that help maintain obese state in a bidirectional crosstalk. Another tightly linked factor is sustained low grade inflammation in tumor microenvironment that is modulated by both obese state and dysbiosis, and influences tumor growth as well as response to immunotherapy. Our review brings together these important aspects and explores their connections. In this review, we discuss how obese state modulates various components of the breast tumor microenvironment and gut microbiota to achieve sustained low-grade inflammation. We explore the crosstalk between different components of tumor microenvironment and microbes, and how they might modulate the response to immunotherapy. Discussing studies from multiple tumor types, we delve to find common microbial characteristics that may positively or negatively influence immunotherapy efficacy in breast cancer and may guide future studies.
Assuntos
Disbiose , Microbioma Gastrointestinal , Imunoterapia , Inflamação , Obesidade , Microambiente Tumoral , Humanos , Disbiose/imunologia , Obesidade/imunologia , Obesidade/terapia , Obesidade/microbiologia , Microambiente Tumoral/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Imunoterapia/métodos , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , FemininoRESUMO
Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology.
Assuntos
Doença de Alzheimer , Periodontite , Porphyromonas gingivalis , Doença de Alzheimer/microbiologia , Doença de Alzheimer/metabolismo , Humanos , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Disbiose/microbiologia , Infecções Bacterianas/microbiologia , Barreira Hematoencefálica/microbiologia , Animais , MicrobiotaRESUMO
Chemotherapy is associated with the induction of intestinal microbiota dysbiosis and gastrointestinal injuries. In this Cell Host & Microbe issue, Anderson et al. demonstrate that chemotherapy-induced epithelial cell apoptosis drives microbiota imbalance and transcriptional rewiring, which in turn delays intestinal recovery.
Assuntos
Disbiose , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Antineoplásicos/uso terapêutico , Animais , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/efeitos dos fármacosRESUMO
Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.
Assuntos
Disfunção Cognitiva , Dieta Hiperlipídica , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Polissacarídeos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Disfunção Cognitiva/terapia , Polissacarídeos/farmacologia , Masculino , Disbiose/terapia , Colo/microbiologia , Escherichia coli , Butiratos/metabolismo , Proteobactérias/isolamento & purificação , Proteobactérias/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.
Assuntos
Biomarcadores , Microbioma Gastrointestinal , Probióticos , Humanos , Gravidez , Feminino , Probióticos/uso terapêutico , Hipertensão Induzida pela Gravidez/microbiologia , Disbiose , Animais , Fibras na DietaRESUMO
BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.
Assuntos
Antivirais , Bactérias , Disbiose , Fezes , Microbioma Gastrointestinal , Hepatite B Crônica , Tenofovir , Humanos , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B Crônica/microbiologia , Adulto , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/microbiologia , Fezes/virologia , RNA Ribossômico 16S/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacosRESUMO
The role of gut microbiota in health and disease is being thoroughly examined in various contexts, with a specific focus on the bacterial fraction due to its significant abundance. However, despite their lower abundance, viruses within the gut microbiota are gaining recognition for their crucial role in shaping the structure and function of the intestinal microbiota, with significant effects on the host as a whole, particularly the immune system. Similarly, environmental factors such as stress are key in modulating the host immune system, which in turn influences the composition of the gut virome and neurological functions through the bidirectional communication of the gut-brain axis. In this context, alterations in the host immune system due to stress and/or dysbiosis of the gut virome are critical factors in the development of both infectious and noninfectious diseases. The molecular mechanisms and correlation patterns between microbial species are not yet fully understood. This literature review seeks to explore the interconnected relationship between stress and the gut virome, with a focus on how this interaction is influenced by the host's immune system. We also discuss how disturbances in this finely balanced system can lead to the onset and/or progression of diseases.
Assuntos
Disbiose , Microbioma Gastrointestinal , Estresse Fisiológico , Viroma , Humanos , Microbioma Gastrointestinal/fisiologia , Doenças Transmissíveis/virologia , Doenças Transmissíveis/microbiologia , Animais , Vírus/classificaçãoRESUMO
The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body's response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome's role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome's function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.
Assuntos
Microbioma Gastrointestinal , Medicina de Precisão , Biologia de Sistemas , Humanos , Microbioma Gastrointestinal/fisiologia , Medicina de Precisão/métodos , Biologia de Sistemas/métodos , Aprendizado de Máquina , Disbiose , Glicemia/análise , Diabetes Mellitus/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Hipoglicemiantes/uso terapêuticoRESUMO
This comprehensive review undertakes a multidisciplinary exploration of the gut-lung axis, from the foundational aspects of anatomy, embryology, and histology, through the functional dynamics of pathophysiology, to implications for clinical science. The gut-lung axis, a bidirectional communication pathway, is central to understanding the interconnectedness of the gastrointestinal- and respiratory systems, both of which share embryological origins and engage in a continuous immunological crosstalk to maintain homeostasis and defend against external noxa. An essential component of this axis is the mucosa-associated lymphoid tissue system (MALT), which orchestrates immune responses across these distant sites. The review delves into the role of the gut microbiome in modulating these interactions, highlighting how microbial dysbiosis and increased gut permeability ("leaky gut") can precipitate systemic inflammation and exacerbate respiratory conditions. Moreover, we thoroughly present the implication of the axis in oncological practice, particularly in lung cancer development and response to cancer immunotherapies. Our work seeks not only to synthesize current knowledge across the spectrum of science related to the gut-lung axis but also to inspire future interdisciplinary research that bridges gaps between basic science and clinical application. Our ultimate goal was to underscore the importance of a holistic understanding of the gut-lung axis, advocating for an integrated approach to unravel its complexities in human health and disease.
Assuntos
Microbioma Gastrointestinal , Imunoterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Microbioma Gastrointestinal/imunologia , Imunoterapia/métodos , Animais , Pulmão/imunologia , Disbiose/imunologia , Pesquisa Translacional BiomédicaRESUMO
Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.
Assuntos
Dermatite Atópica , Disbiose , Pele , Staphylococcus aureus , Dermatite Atópica/microbiologia , Dermatite Atópica/imunologia , Humanos , Staphylococcus aureus/imunologia , Staphylococcus aureus/fisiologia , Pele/microbiologia , Pele/imunologia , Pele/patologia , Disbiose/microbiologia , Disbiose/imunologia , Microbiota/imunologia , Animais , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaRESUMO
Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.