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1.
Nat Commun ; 15(1): 4708, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830853

ABSTRACT

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.


Subject(s)
COVID-19 , Dysbiosis , Gastrointestinal Microbiome , Lung , Microbiota , Humans , Female , Male , Dysbiosis/microbiology , Middle Aged , Lung/microbiology , COVID-19/microbiology , COVID-19/virology , Aged , Microbiota/genetics , Gastrointestinal Microbiome/genetics , Host Microbial Interactions/genetics , Longitudinal Studies , RNA, Ribosomal, 16S/genetics , Respiratory Insufficiency/microbiology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adult , Respiration, Artificial , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Critical Illness , Metagenomics/methods
2.
BMC Microbiol ; 24(1): 192, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831399

ABSTRACT

BACKGROUND: HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have sex with men (MSM), as well as the effects of HIV and antiretroviral therapy (ART) on their gut microbiota, remains under active study. Thus, our research focuses on clarifying the distinctions in intestinal microbiota composition among uninfected MSM and non-MSM healthy controls, investigating the alterations in early-stage intestinal microbial communities following HIV infection, and assessing how ART affects the intestinal microbiota. METHODS: This study enrolled four participant groups: uninfected MSM, Recent HIV-1 infection (RHI) MSM, MSM on ART, and non-MSM healthy controls, with 30 individuals in each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal microbiota and employed Luminex multiplex assays to measure plasma markers for microbial translocation (LBP, sCD14) and the inflammatory marker CRP. FINDINGS: Comparing uninfected MSM to non-MSM healthy controls, no substantial variances were observed in α and ß diversity. Uninfected MSM had higher average relative abundances of Bacteroidetes, Prevotella, and Alloprevotella, while Bacteroides, Firmicutes, and Faecalibacterium had lower average relative abundances. MSM on ART had lower intestinal microbiota diversity than RHI MSM and uninfected MSM. In MSM on ART, Megasphaera and Fusobacterium increased, while Faecalibacterium and Roseburia decreased at genus level. Additionally, treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) led to significant alterations in intestinal microbiota diversity and composition compared to RHI MSM. The random forest model showed that HIV infection biomarkers effectively distinguished between newly diagnosed HIV-infected MSM and HIV-negative MSM, with an ROC AUC of 76.24% (95% CI: 61.17-91.31%). CONCLUSIONS: MSM showed early intestinal microbiota imbalances after new HIV infection. MSM on ART experienced worsened dysbiosis, indicating a combined effect of HIV and ART. NNRTI-based treatment notably changed intestinal microbiota, suggesting a potential direct impact of NNRTI drugs on intestinal microbiota.


Subject(s)
Gastrointestinal Microbiome , HIV Infections , Homosexuality, Male , RNA, Ribosomal, 16S , Humans , Male , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , HIV Infections/microbiology , HIV Infections/drug therapy , HIV Infections/complications , Adult , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/drug effects , Feces/microbiology , Feces/virology , Middle Aged , HIV-1/genetics , Dysbiosis/microbiology
3.
Appl Microbiol Biotechnol ; 108(1): 362, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842702

ABSTRACT

Intestinal microbiome contains several times of functional genes compared to the host and mediates the generation of multiple metabolic products, and therefore it is called "second genome" for host. Crustaceans rank second among the largest subphylum of aquaculture animals that are considered potentially satisfy global substantial food and nutrition security, among which the Pacific white shrimp (Litopenaeus vannamei) ranks the first in the production. Currently, increasing evidences show that outbreaks of some most devastating diseases in shrimp, including white feces syndrome (WFS) and acute hepatopancreatic necrosis disease (AHPND), are related to intestinal microbiota dysbiosis. Importantly, the intestine microbial composition can be altered by environmental stress, diet, and age. In this review, we overview the progress of intestinal microbiota dysbiosis and WFS or ANPHD in shrimp, and how the microbial composition is altered by external factors. Hence, developing suitable microbial micro-ecological prevention and control strategy to maintain intestinal balance may be a feasible solution to reduce the risk of disease outbreaks. Moreover, we highlight that defining the "healthy intestine microbiota" and evaluating the causality of intestinal microbiota dysbiosis and diseases following the logic of "Microecological Koch's postulates" should be the key goal in future shrimp intestinal field, which help to guide disease diagnosis and prevent disease outbreaks in shrimp farming. KEY POINTS: • Intestinal microbiota dysbiosis is relevant to multiple shrimp diseases. • Microecological Koch's postulates help to evaluate the causality of shrimp diseases.


Subject(s)
Aquaculture , Dysbiosis , Gastrointestinal Microbiome , Penaeidae , Animals , Penaeidae/microbiology , Dysbiosis/microbiology
4.
Microb Ecol ; 87(1): 81, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829379

ABSTRACT

Koinobiont endoparasitoids regulate the physiology of their hosts through altering host immuno-metabolic responses, processes which function in tandem to shape the composition of the microbiota of these hosts. Here, we employed 16S rRNA and ITS amplicon sequencing to investigate whether parasitization by the parasitoid wasps, Diachasmimorpha longicaudata (Ashmaed) (Hymenoptera: Braconidae) and Psyttalia cosyrae (Wilkinson) (Hymenoptera: Braconidae), induces gut dysbiosis and differentially alter the gut microbial (bacteria and fungi) communities of an important horticultural pest, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further investigated the composition of bacterial communities of adult D. longicaudata and P. cosyrae to ascertain whether the adult parasitoids and parasitized host larvae share microbial taxa through transmission. We demonstrated that parasitism by D. longicaudata induced significant gut perturbations, resulting in the colonization and increased relative abundance of pathogenic gut bacteria. Some pathogenic bacteria like Stenotrophomonas and Morganella were detected in both the guts of D. longicaudata-parasitized B. dorsalis larvae and adult D. longicaudata wasps, suggesting a horizontal transfer of microbes from the parasitoid to the host. The bacterial community of P. cosyrae adult wasps was dominated by Arsenophonus nasoniae, whereas that of D. longicaudata adults was dominated by Paucibater spp. and Pseudomonas spp. Parasitization by either parasitoid wasp was associated with an overall reduction in fungal diversity and evenness. These findings indicate that unlike P. cosyrae which is avirulent to B. dorsalis, parasitization by D. longicaudata induces shifts in the gut bacteriome of B. dorsalis larvae to a pathobiont-dominated community. This mechanism possibly enhances its virulence against the pest, further supporting its candidacy as an effective biocontrol agent of this frugivorous tephritid fruit fly pest.


Subject(s)
Bacteria , Gastrointestinal Microbiome , Larva , RNA, Ribosomal, 16S , Tephritidae , Wasps , Animals , Tephritidae/microbiology , Tephritidae/parasitology , Wasps/microbiology , Wasps/physiology , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Larva/microbiology , Larva/parasitology , Larva/growth & development , RNA, Ribosomal, 16S/genetics , Fungi/genetics , Fungi/physiology , Host-Parasite Interactions , Microbiota , Dysbiosis/microbiology , Dysbiosis/parasitology
5.
Sci Rep ; 14(1): 12668, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830904

ABSTRACT

Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse. To this end, we analyzed intestinal biopsy samples from six patients with pediatric Crohn's disease in remission and a control group of 16 pediatric patients with no evident pathogenic abnormality. We identified compositional microbiota differences, including decreases in the genera Streptococcus and Actinobacillus as well as increases in Oribacterium and Prevotella in patients with controlled Crohn's disease compared to controls. Further, a histologic analysis found that patients with controlled Crohn's disease had increased epithelial integrity, and decreased intraepithelial lymphocytes compared with controls. Additionally, we observed increased peripheral CD4+ T cells in patients with pediatric Crohn's disease. These results indicate that markers of intestinal inflammation are responsive to Crohn's disease treatment, however the interventions may not resolve the underlying dysbiosis. These findings suggest that persistent dysbiosis may increase vulnerability to relapse of pediatric Crohn's disease. This study used a nested cohort of patients from the Bangladesh Environmental Enteric Dysfunction (BEED) study (ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016).


Subject(s)
Crohn Disease , Dysbiosis , Gastrointestinal Microbiome , Humans , Crohn Disease/microbiology , Crohn Disease/pathology , Crohn Disease/complications , Dysbiosis/microbiology , Female , Male , Child , Adolescent , Duodenum/microbiology , Duodenum/pathology , Inflammation/microbiology , Inflammation/pathology , Case-Control Studies
6.
Brain Behav ; 14(6): e3579, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38841824

ABSTRACT

BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.


Subject(s)
Feces , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Schizophrenia , Humans , Schizophrenia/microbiology , RNA, Ribosomal, 16S/genetics , Male , Young Adult , Female , Adult , Feces/microbiology , Dysbiosis/microbiology
7.
Curr Opin Gastroenterol ; 40(4): 258-267, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38841848

ABSTRACT

PURPOSE OF REVIEW: The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis. RECENT FINDINGS: This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use. SUMMARY: The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.


Subject(s)
Dysbiosis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Humans , Fecal Microbiota Transplantation/methods , Dysbiosis/therapy , Dysbiosis/microbiology , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/therapy , Randomized Controlled Trials as Topic
8.
Oral Oncol ; 154: 106864, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824812

ABSTRACT

OBJECTIVE: To compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. STUDY DESIGN: Prospective cohort study. SETTING: Unicenter, Tertiary referral hospital. METHODS: Included patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) RESULTS: Total of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). CONCLUSIONS: This is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.


Subject(s)
Dysbiosis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Dysbiosis/microbiology , Dysbiosis/etiology , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/microbiology , Pilot Projects , Prospective Studies , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/microbiology , Adult , Aged , Microbiota/radiation effects , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods
9.
Gut Microbes ; 16(1): 2361490, 2024.
Article in English | MEDLINE | ID: mdl-38860456

ABSTRACT

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Mycobacterium Infections, Nontuberculous , Toll-Like Receptor 2 , Dysbiosis/microbiology , Animals , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Humans , Mice , Male , Female , Mycobacterium Infections, Nontuberculous/microbiology , Middle Aged , Feces/microbiology , Aged , Prevotella , Lung Diseases/microbiology , Nontuberculous Mycobacteria , Disease Susceptibility , Mice, Inbred C57BL , Lung/microbiology
10.
Nat Commun ; 15(1): 4889, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849369

ABSTRACT

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Pulmonary exacerbations (PEx) in these conditions are associated with accelerated lung function decline and higher mortality rates. Understanding PEx ecology is challenged by high inter-patient variability in airway microbial community profiles. We analyze bacterial communities in 880 CF sputum samples collected during an observational prospective cohort study and develop microbiome descriptors to model community reorganization prior to and during 18 PEx. We identify two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx show hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx display stochasticity and increased diversity. A simulation of antimicrobial treatment predicts better efficacy for hierarchically organized communities. This link between PEx, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases.


Subject(s)
Cystic Fibrosis , Dysbiosis , Microbiota , Sputum , Cystic Fibrosis/microbiology , Humans , Male , Sputum/microbiology , Prospective Studies , Female , Treatment Outcome , Dysbiosis/microbiology , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Lung/microbiology , Disease Progression , Pulmonary Disease, Chronic Obstructive/microbiology , Young Adult , Adolescent , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
11.
BMC Microbiol ; 24(1): 201, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851693

ABSTRACT

BACKGROUND: People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition. RESULTS: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories. CONCLUSIONS: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.


Subject(s)
Gastrointestinal Microbiome , HIV Infections , Adult , Female , Humans , Male , Middle Aged , Bacteria/genetics , Bacteria/classification , Bacteria/drug effects , Bacteria/isolation & purification , Dysbiosis/microbiology , Feces/microbiology , Feces/virology , Gastrointestinal Microbiome/genetics , HIV Infections/microbiology , HIV Infections/virology , HIV Infections/complications , HIV-1/genetics , HIV-1/drug effects , Homosexuality, Male , Metagenomics , Prevotella/genetics , Prevotella/isolation & purification , Sexual Behavior , Spain
12.
Sci Rep ; 14(1): 12903, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839848

ABSTRACT

Free Fecal Liquid (FFL), also termed Fecal Water Syndrome (FWS), is an ailment in horses characterized by variable solid and liquid (water) phases at defecation. The liquid phase can be excreted before, during, or after the solid defecation phase. While the underlying causes of FFL are unknown, hindgut dysbiosis is suggested to be associated with FFL. Three European studies investigated dysbiosis in horses with FFL using 16S rRNA sequencing and reported results that conflicted between each other. In the present study, we also used 16S rRNA sequencing to study the fecal microbial composition in 14 Canadian horses with FFL, and 11 healthy stable mate controls. We found no significant difference in fecal microbial composition between FFL and healthy horses, which further supports that dysbiosis is not associated with FFL.


Subject(s)
Dysbiosis , Feces , RNA, Ribosomal, 16S , Horses , Animals , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Dysbiosis/microbiology , Dysbiosis/veterinary , Horse Diseases/microbiology , Male , Canada , Female , Gastrointestinal Microbiome/genetics
13.
Sci Rep ; 14(1): 13381, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862570

ABSTRACT

To establish and evaluate an intestinal microbiota dysbiosis-induced obesity mouse model. 50 C57BL/6 J male healthy mice were randomly divided into an obesity model group and the control group. The body weight, body length, and Lee's index of the two groups of mice at week 1 and week 10 were compared. Serum glucose (GLU), total cholesterol (TC) and triglyceride (TG) were measured by enzyme-labeled colorimetric methods. Illumina HiSeq 16S rDNA high-throughput sequencing technology was used to characterize intestinal microbiota in feces. The success rate of model establishment in obese mice was 52%. The body weight, body length, Lee's index, and abdominal fat (wet weight) in the obese model group were all higher than those in the control group, and the differences were statistically significant (P < 0.01). Serum GLU and TC levels in the obesity model group were higher than those in the control group (P < 0.05), and there was no difference in TG levels between the two groups (P > 0.05). The control group contained more abundant intestinal microbiota phyla and genera than did the obesity model group; the differences between the two groups were significant (FDR ≤ 0.05, P ≤ 0.05). Intestinal microbiota dysbiosis can be used to generate an obesity model in mice.


Subject(s)
Disease Models, Animal , Dysbiosis , Gastrointestinal Microbiome , Mice, Inbred C57BL , Obesity , Animals , Obesity/microbiology , Dysbiosis/microbiology , Male , Mice , Body Weight , Feces/microbiology , Blood Glucose/metabolism , Triglycerides/blood , RNA, Ribosomal, 16S/genetics , Mice, Obese
14.
Microbiome ; 12(1): 85, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38725043

ABSTRACT

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD. RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10-5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD. CONCLUSION: In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity. Video Abstract.


Subject(s)
Gastrointestinal Microbiome , Hispanic or Latino , Ventricular Dysfunction, Left , Humans , Female , Middle Aged , Male , Ventricular Dysfunction, Left/microbiology , Ventricular Dysfunction, Left/blood , United States , Dysbiosis/microbiology , Aged , Bacteria/classification , Bacteria/isolation & purification , Metabolome , Echocardiography
15.
J Appl Microbiol ; 135(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38755019

ABSTRACT

AIM: The present study is a single-centre, randomized, controlled clinical trial aimed to evaluate the effectiveness of the probiotic Lacticaseibacillus rhamnosus TOM 22.8 (DSM 33500) strain, orally administrated, to treat vaginal dysbiosis. METHODS AND RESULTS: Overall, 80 women, with signs and symptoms of vaginal dysbiosis, were enrolled and allocated to the treatment group (A, n=60), who took 1 capsule of the probiotic strain for 10 consecutive days, or the non-treatment group (B, n=20), who did not receive any treatment. Clinical (vaginal signs and symptoms; pH of the vaginal fluid; Amsel criteria; Nugent score; Lactobacillary grade) and microbiological examinations were performed at baseline (T0), 10 days (T1), and 30 (T2) days after the oral administration of the probiotic TOM 22.8 strain. The latter resulted in a restoration of the physiological pH, accompanied by remission or attenuation of clinical signs and symptoms as well as the improvement of the quality of life (QoL). Microbiological data revealed a significant reduction of potentially pathogenic bacteria. CONCLUSION: The administration of the L. rhamnosus TOM 22.8 probiotic strain could be proposed as an effective strategy for the treatment of vaginal dysbiosis.


Subject(s)
Dysbiosis , Lacticaseibacillus rhamnosus , Probiotics , Vagina , Female , Humans , Probiotics/administration & dosage , Probiotics/therapeutic use , Dysbiosis/microbiology , Vagina/microbiology , Adult , Middle Aged , Young Adult , Quality of Life , Lactobacillus , Vaginosis, Bacterial/microbiology , Vaginosis, Bacterial/drug therapy
16.
Elife ; 122024 May 01.
Article in English | MEDLINE | ID: mdl-38690990

ABSTRACT

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.


Subject(s)
Bacteria , Cesarean Section , Cicatrix , Diverticulum , Female , Cesarean Section/adverse effects , Humans , Diverticulum/microbiology , Diverticulum/metabolism , Bacteria/metabolism , Bacteria/genetics , Cicatrix/microbiology , Cicatrix/metabolism , Dysbiosis/microbiology , Fungi/metabolism , Fungi/genetics , Fungi/physiology , Microbial Interactions , Microbiota
17.
Sci Rep ; 14(1): 10394, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38710815

ABSTRACT

Tobacco use significantly influences the oral microbiome. However, less is known about how different tobacco products specifically impact the oral microbiome over time. To address this knowledge gap, we characterized the oral microbiome of cigarette users, smokeless tobacco users, and non-users over 4 months (four time points). Buccal swab and saliva samples (n = 611) were collected from 85 participants. DNA was extracted from all samples and sequencing was carried out on an Illumina MiSeq, targeting the V3-V4 region of the 16S rRNA gene. Cigarette and smokeless tobacco users had more diverse oral bacterial communities, including a higher relative abundance of Firmicutes and a lower relative abundance of Proteobacteria, when compared to non-users. Non-users had a higher relative abundance of Actinomyces, Granulicatella, Haemophilus, Neisseria, Oribacterium, Prevotella, Pseudomonas, Rothia, and Veillonella in buccal swab samples, compared to tobacco users. While the most abundant bacterial genera were relatively constant over time, some species demonstrated significant shifts in relative abundance between the first and last time points. In addition, some opportunistic pathogens were detected among tobacco users including Neisseria subflava, Bulleidia moorei and Porphyromonas endodontalis. Overall, our results provide a more holistic understanding of the structure of oral bacterial communities in tobacco users compared to non-users.


Subject(s)
Dysbiosis , Microbiota , Mouth , RNA, Ribosomal, 16S , Tobacco, Smokeless , Humans , Tobacco, Smokeless/adverse effects , Male , Female , Dysbiosis/microbiology , Adult , RNA, Ribosomal, 16S/genetics , Mouth/microbiology , Saliva/microbiology , Middle Aged , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Smokers , Young Adult , Cigarette Smoking/adverse effects , Mouth Mucosa/microbiology
18.
EBioMedicine ; 103: 105137, 2024 May.
Article in English | MEDLINE | ID: mdl-38703606

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. METHODS: In this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FINDINGS: Based on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. INTERPRETATION: In conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FUNDING: This work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202417, Ggyfz202308), the Beijing Natural Science Foundation (No. 7222068); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).


Subject(s)
Coronary Artery Disease , Gastrointestinal Microbiome , Mycobiome , Humans , Coronary Artery Disease/microbiology , Male , Female , Middle Aged , Aged , Cross-Sectional Studies , Feces/microbiology , Metagenomics/methods , Fungi/genetics , Fungi/classification , Fungi/isolation & purification , Severity of Illness Index , Dysbiosis/microbiology , Case-Control Studies , RNA, Ribosomal, 16S/genetics , Adult
19.
Gut Microbes ; 16(1): 2351503, 2024.
Article in English | MEDLINE | ID: mdl-38748594

ABSTRACT

C-section is crucial in reducing maternal and neonatal mortality when medically indicated, but one of its side effects could be the disruption of vertical transmission of maternal-infant microbiota during delivery, potentially leading to gut dysbiosis and increased disease risks in C-section infants. To address such dysbiosis, it seems reasonable to supplement "what is missing" during C-section procedure. This idea has prompted several clinical trials, including proof-of-concept, investigating interventions like vaginal microbial seeding, oral administration of maternal vaginal microbes and even oral administration of maternal fecal materials. Hereby, we have summarized these trials to help understand the current state of these researches, highlighting the predominantly pilot nature of most of these studies and emphasizing the need for well-designed studies with larger sample to guide evidence-based medicine in the future.


C-section is associated with gut dysbiosis in CS infants and increased disease risks from childhood to adulthood.Apart from using traditional probiotics to restore CS-related dysbiosis, a new research direction is to investigate the potential of mimicking natural inoculation process would alleviate infant gut dysbiosis.Several small-scale studies have shown that transplanting maternal vaginal or even fecal microbiota might restore CS-related infant dysbiosis. Controversy remains regarding the clinical applicability, safety, efficacy and mechanisms of these approaches.


Subject(s)
Cesarean Section , Dysbiosis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Humans , Dysbiosis/microbiology , Female , Cesarean Section/adverse effects , Pregnancy , Infant, Newborn , Vagina/microbiology , Infant
20.
BMC Microbiol ; 24(1): 161, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730357

ABSTRACT

Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.


Subject(s)
Diabetes, Gestational , Dysbiosis , Fatty Acids, Volatile , Gastrointestinal Microbiome , Diabetes, Gestational/microbiology , Diabetes, Gestational/metabolism , Humans , Pregnancy , Female , Dysbiosis/microbiology , Fatty Acids, Volatile/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Bacteria/isolation & purification , Host Microbial Interactions , Lipopolysaccharides/metabolism
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