RESUMEN
Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment.
Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Pie Diabético , Disbiosis , Heces , Microbioma Gastrointestinal , Micobioma , Humanos , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/complicaciones , Persona de Mediana Edad , Femenino , Masculino , Disbiosis/microbiología , Disbiosis/diagnóstico , Pie Diabético/microbiología , Biomarcadores/sangre , Heces/microbiología , Anciano , Adulto , Ascomicetos , Basidiomycota , Estudios de Casos y Controles , Hongos/aislamiento & purificaciónRESUMEN
Background: Hepatic encephalopathy (HE) is a neurological disorder resulting from advanced liver injury. HE has a high mortality rate and poor prognosis. The pathogenesis of HE is still unclear, which has led to the lack of a satisfactory specific treatment method. There is increasing evidence that the intestinal flora affects the communication between the gut and the brain in the pathogenesis of HE. Adjusting the intestinal flora has had a beneficial effect on HE in recent studies, and the Qingchang Ligan formula (QCLG) has been shown in previous studies to regulate intestinal flora and metabolites. In this study, we established a thioacetamide-induced HE mouse model to evaluate the protective effect of QCLG on HE and explore its potential mechanism, which also demonstrated that intestinal flora dysbiosis is involved in the pathogenesis of HE. Methods: Mice were intraperitoneally injected with thioacetamide (TAA, 150 mg/kg) to induce HE. Additionally, they were orally administered Qingchang Ligan Formula (QCLG) at a dose of 6.725 g/kg·d for seven days, while control mice received an equal volume of saline via gavage. Subsequently, samples were subjected to 16S ribosomal ribonucleic acid (rRNA) gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS), and RNA-sequencing (RNA-seq) analysis. Result: QCLG improved weight loss, cognitive impairment, neurological function scores, blood ammonia, and brain gene expression of interleukin-6 (TNF-α), Interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) induced by HE. Moreover, QCLG increased the levels of liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum TNF-α, IL-1ß, and IL-6. 16S RNA sequencing revealed increased Oscillibacter, Colidextribacter, and Helicobacter in TAA-induced mouse fecal samples. Also, the abundance of Bifidobacterium decreases TAA-induced mouse fecal samples. In contrast, QCLG treatment significantly restored the gut microbial community. Metabolomics indicated significant differences in some metabolites among the normal control, treatment, and model groups, including 5-methoxytryptophan, Daidzein, Stercobilin, and Plumieride (PLU). Conclusion: QCLG can alleviate neuroinflammation and prevent HE caused by liver injury by regulating intestinal flora in mouse models.
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Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Encefalopatía Hepática , Metabolómica , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Medicamentos Herbarios Chinos/farmacología , Masculino , Tioacetamida/toxicidad , Disbiosis/microbiología , ARN Ribosómico 16S/genética , Ratones Endogámicos C57BLRESUMEN
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.
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Sulfato de Dextran , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Factor 1 Inducible por Hipoxia , Mucosa Intestinal , Transducción de Señal , Vitamina B 12 , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Ratones , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Transducción de Señal/efectos de los fármacos , Sulfato de Dextran/toxicidad , Factor 1 Inducible por Hipoxia/metabolismo , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/microbiología , Colitis/patología , Colitis/tratamiento farmacológico , Disbiosis/microbiología , Disbiosis/metabolismo , Ratones Endogámicos C57BL , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Drosophila/metabolismoRESUMEN
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.
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Disbiosis , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Obesidad , Probióticos , Humanos , Disbiosis/microbiología , Disbiosis/terapia , Obesidad/microbiología , Probióticos/uso terapéutico , Animales , Inflamación/microbiología , Prebióticos/administración & dosificaciónRESUMEN
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Despite of a steadily increasing in morbidity and mortality, there is still no effective therapy. Gut microbial dysbiosis and its derived-metabolites disorder have been shown to play an important role in the development of AP, however, little is known regarding the crosstalk between gut microbiota and metabolites. In this study, we assessed the alterations in gut microbiota and metabolites by constructing three AP mouse models by means of metagenomic and metabolomic sequencing, and further clarified their relationship by correlation analysis. The results revealed that each model exhibited unique flora and metabolite profiles. KEGG analysis showed that the differential flora and metabolite-enriched pathway functions were correlated with lipid metabolism and amino acid metabolism. Moreover, two core differential bacterial species on Burkholderiales bacterium YL45 and Bifidobacterium pseudolongum along with eleven differential metabolites appeared to exert certain effects during the course of AP. In conclusion, further exploration of the crosstalk between microbiota and derived metabolites may provide novel insights and strategies into the diagnosis and treatment of AP.
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Microbioma Gastrointestinal , Metabolómica , Metagenómica , Pancreatitis , Pancreatitis/microbiología , Pancreatitis/metabolismo , Animales , Metabolómica/métodos , Metagenómica/métodos , Ratones , Metaboloma , Modelos Animales de Enfermedad , Disbiosis/microbiología , Disbiosis/metabolismo , Ratones Endogámicos C57BL , Masculino , Enfermedad AgudaRESUMEN
Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.
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Microbioma Gastrointestinal , Infecciones por VIH , VIH-1 , Homosexualidad Masculina , Inflamación , Conducta Sexual , Masculino , Humanos , Infecciones por VIH/microbiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Adulto , Inflamación/microbiología , VIH-1/fisiología , Disbiosis/microbiología , Persona de Mediana EdadRESUMEN
The deleterious impact of antibiotics (ATB) on the microbiome negatively influences immune checkpoint inhibitors (ICI) response in patients with cancer. We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. The primary objective of the study was to assess the effect of DAV132 on ATB plasma concentrations and both doses of DAV132 did not alter ATB levels. Secondary objectives included safety, darkening of the feces, and fecal ATB concentrations. DAV132 was well tolerated, with no severe toxicity and similar darkening at both DAV132 doses. DAV132 led to significant decrease in CZA or PTZ feces concentration. When co-administered with CZA or PTZ, DAV132 preserved microbiome diversity, accelerated recovery to baseline composition and protected key commensals. Fecal microbiota transplantation (FMT) in preclinical cancer models in female mice from HV treated with CZA or PTZ alone inhibited anti-PD-1 response, while transplanted samples from HV treated with ATB + DAV132 circumvented resistance to anti-PD-1. This effect was linked to activated CD8+ T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients.
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Antibacterianos , Colon , Disbiosis , Heces , Microbioma Gastrointestinal , Voluntarios Sanos , Humanos , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Animales , Disbiosis/microbiología , Disbiosis/inducido químicamente , Femenino , Ratones , Adulto , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Colon/microbiología , Colon/efectos de los fármacos , Heces/microbiología , Heces/química , Persona de Mediana Edad , Trasplante de Microbiota Fecal , Adulto Joven , Inhibidores de Puntos de Control InmunológicoRESUMEN
The lungs, as vital organs in the human body, continuously engage in gas exchange with the external environment. The lung microbiota, a critical component in maintaining internal homeostasis, significantly influences the onset and progression of diseases. Beneficial interactions between the host and its microbial community are essential for preserving the host's health, whereas disease development is often linked to dysbiosis or alterations in the microbial community. Evidence has demonstrated that changes in lung microbiota contribute to the development of major chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung cancer. However, in-depth mechanistic studies are constrained by the small scale of the lung microbiota and its susceptibility to environmental pollutants and other factors, leaving many questions unanswered. This review examines recent research on the lung microbiota and lung diseases, as well as methodological advancements in studying lung microbiota, summarizing the ways in which lung microbiota impacts lung diseases and introducing research methods for investigating lung microbiota.
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Disbiosis , Enfermedades Pulmonares , Pulmón , Microbiota , Humanos , Pulmón/microbiología , Enfermedades Pulmonares/microbiología , Disbiosis/microbiología , Enfermedad Crónica , Animales , Enfermedad Pulmonar Obstructiva Crónica/microbiologíaRESUMEN
BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood. OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms. METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum. RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice. CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.
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Dieta Alta en Grasa , Disbiosis , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Microesferas , Obesidad , Poliestirenos , Animales , Disbiosis/microbiología , Ratones , Obesidad/microbiología , Poliestirenos/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Microplásticos/toxicidad , ARN Ribosómico 16SRESUMEN
Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10-/- mice, model of spontaneous colitis. Using an in vitro microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential. In vivo investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages' associated proinflammatory cytokines (TNF, IL-6, and IL-1ß). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly, in vivo inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.
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Colitis , Heces , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Animales , Humanos , Heces/microbiología , Ratones , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/metabolismo , Colitis/microbiología , Colitis/inducido químicamente , Colitis/genética , Inflamación/microbiología , Inflamación/metabolismo , Disbiosis/microbiología , Ratones Endogámicos C57BL , Femenino , Ratones Noqueados , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Masculino , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Citocinas/metabolismo , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Interleucina-10/genética , Interleucina-10/metabolismoRESUMEN
Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.
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Bacteroides , Colon , Sulfato de Dextran , Modelos Animales de Enfermedad , Heces , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Probióticos , Animales , Probióticos/farmacología , Humanos , Colon/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Bacteroides/aislamiento & purificación , Heces/microbiología , Masculino , Colitis/microbiología , Colitis/inducido químicamente , Disbiosis/microbiología , Colitis Ulcerosa/microbiologíaRESUMEN
Autism Spectrum Disorder (ASD) is a multifactorial disorder involving genetic and environmental factors leading to pathophysiologic symptoms and comorbidities including neurodevelopmental disorders, anxiety, immune dysregulation, and gastrointestinal (GI) abnormalities. Abnormal intestinal permeability has been reported among ASD patients and it is well established that disturbances in eating patterns may cause gut microbiome imbalance (i.e., dysbiosis). Therefore, studies focusing on the potential relationship between gut microbiota and ASD are emerging. We compared the intestinal bacteriome and mycobiome of a cohort of ASD subjects with their non-ASD siblings. Differences between ASD and non-ASD subjects include a significant decrease at the phylum level in Cyanobacteria (0.015% vs. 0.074%, p < 0.0003), and a significant decrease at the genus level in Bacteroides (28.3% vs. 36.8%, p < 0.03). Species-level analysis showed a significant decrease in Faecalibacterium prausnitzii, Prevotella copri, Bacteroides fragilis, and Akkermansia municiphila. Mycobiome analysis showed an increase in the fungal Ascomycota phylum (98.3% vs. 94%, p < 0.047) and an increase in Candida albicans (27.1% vs. 13.2%, p < 0.055). Multivariate analysis showed that organisms from the genus Delftia were predictive of an increased odds ratio of ASD, whereas decreases at the phylum level in Cyanobacteria and at the genus level in Azospirillum were associated with an increased odds ratio of ASD. We screened 24 probiotic organisms to identify strains that could alter the growth patterns of organisms identified as elevated within ASD subject samples. In a preliminary in vivo preclinical test, we challenged wild-type Balb/c mice with Delftia acidovorans (increased in ASD subjects) by oral gavage and compared changes in behavioral patterns to sham-treated controls. An in vitro biofilm assay was used to determine the ability of potentially beneficial microorganisms to alter the biofilm-forming patterns of Delftia acidovorans, as well as their ability to break down fiber. Downregulation of cyanobacteria (generally beneficial for inflammation and wound healing) combined with an increase in biofilm-forming species such as D. acidovorans suggests that ASD-related GI symptoms may result from decreases in beneficial organisms with a concomitant increase in potential pathogens, and that beneficial probiotics can be identified that counteract these changes.
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Trastorno del Espectro Autista , Microbioma Gastrointestinal , Micobioma , Hermanos , Trastorno del Espectro Autista/microbiología , Humanos , Femenino , Masculino , Niño , Animales , Ratones , Preescolar , Disbiosis/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Candida albicans/aislamiento & purificación , Heces/microbiologíaRESUMEN
The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.
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Dieta , Microbioma Gastrointestinal , Inflamación , Humanos , Inflamación/microbiología , Disbiosis/microbiología , Animales , Dieta Mediterránea , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/etiología , Dieta Occidental/efectos adversosRESUMEN
Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut-brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.
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Microbioma Gastrointestinal , Enfermedades Neurodegenerativas , Probióticos , Humanos , Enfermedades Neurodegenerativas/microbiología , Enfermedades Neurodegenerativas/metabolismo , Probióticos/uso terapéutico , Disbiosis/microbiología , Eje Cerebro-Intestino , AnimalesRESUMEN
Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.
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Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Metaboloma , Humanos , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/genética , Disbiosis/microbiología , AnimalesRESUMEN
Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium, Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.
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Biomarcadores , Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Medicina de Precisión , Humanos , Disbiosis/microbiología , Niño , Femenino , Masculino , Enfermedades Inflamatorias del Intestino/microbiología , Adolescente , Medicina de Precisión/métodos , ARN Ribosómico 16S/genética , Heces/microbiología , Preescolar , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Íleon/microbiología , Íleon/patología , Colitis Ulcerosa/microbiologíaRESUMEN
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.
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Enfermedad de Alzheimer , Periodontitis , Porphyromonas gingivalis , Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/metabolismo , Humanos , Periodontitis/microbiología , Porphyromonas gingivalis/patogenicidad , Disbiosis/microbiología , Infecciones Bacterianas/microbiología , Barrera Hematoencefálica/microbiología , Animales , MicrobiotaRESUMEN
BACKGROUND: Klebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied. METHODS: A preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis. RESULTS: K. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae-infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain. Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic "pathobiome" signature implicated in gut-brain perturbations. CONCLUSIONS: The findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier.
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Enfermedad de Alzheimer , Barrera Hematoencefálica , Modelos Animales de Enfermedad , Disbiosis , Microbioma Gastrointestinal , Infecciones por Klebsiella , Klebsiella pneumoniae , Ratones Transgénicos , Enfermedades Neuroinflamatorias , Animales , Ratones , Disbiosis/microbiología , Disbiosis/inducido químicamente , Enfermedad de Alzheimer/microbiología , Enfermedades Neuroinflamatorias/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Infecciones por Klebsiella/microbiología , Barrera Hematoencefálica/microbiología , Encéfalo/patología , Encéfalo/microbiología , Antibacterianos/farmacología , Eje Cerebro-Intestino , Masculino , HumanosRESUMEN
Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.
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Bacterias , Disbiosis , Heces , Microbioma Gastrointestinal , Metagenómica , Disbiosis/microbiología , Humanos , Metagenómica/métodos , Suecia , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Heces/microbiología , Estudios Longitudinales , Metagenoma , Adulto , Reactores Biológicos/microbiología , FermentaciónRESUMEN
Dysbiosis within microbiomes has been increasingly implicated in many systemic illnesses, such as cardiovascular disease, metabolic syndrome, respiratory infections, and Alzheimer disease (Ad). The correlation between Ad and microbial dysbiosis has been repeatedly shown, yet the etiologic cause of microbial dysbiosis remains elusive. From a neuropathology perspective, abnormal (often age-related) changes in the brain, associated structures, and bodily lumens tend toward an accumulation of oxygen-depleted pathologic structures, which are anaerobically selective niches. These anaerobic environments may promote progressive change in the microbial community proximal to the brain and thus deserve further investigation. In this review, we identify and explore what is known about the anaerobic niche near or associated with the brain and the anaerobes that it is harbors. We identify the anaerobe stakeholders within microbiome communities and the impacts on the neurodegenerative processes associated with Ad. Chronic oral dysbiosis in anaerobic dental pockets and the composition of the gut microbiota from fecal stool are the 2 largest anaerobic niche sources of bacterial transference to the brain. At the blood-brain barrier, cerebral atherosclerotic plaques are predominated by anaerobic species intimately associated with the brain vasculature. Focal cerebritis/brain abscess and corpora amylacea may also establish chronic anaerobic niches in direct proximity to brain parenchyma. In exploring the anaerobic niche proximal to the brain, we identify research opportunities to explore potential sources of microbial dysbiosis associated with Ad.