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Science Translational Medicine Nov 2023Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation... (Randomized Controlled Trial)
Randomized Controlled Trial
Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (, , , , species, , , and ) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.
Topics: Humans; Fecal Microbiota Transplantation; Anti-Bacterial Agents; Gastrointestinal Microbiome; Drug Resistance, Bacterial; Feces; Treatment Outcome
PubMed: 37910603
DOI: 10.1126/scitranslmed.abo2750 -
Frontiers in Cellular and Infection... 2023There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a...
BACKGROUND
There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis.
METHODS
30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together.
RESULTS
There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were , and . The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism.
CONCLUSION
This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.
Topics: Humans; Child; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Metabolomics; Bacteria; Metagenomics; Gastroesophageal Reflux
PubMed: 37900308
DOI: 10.3389/fcimb.2023.1267192 -
Frontiers in Microbiology 2024The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the...
INTRODUCTION
The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators.
METHODS
The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) ( = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) ( = 29,266, = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations ( = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators.
RESULTS
Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and = 0.018; "IgD- CD27- B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and = 0.029; "CD20- CD38- B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and = 0.021.
CONCLUSION
This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells.
PubMed: 38765682
DOI: 10.3389/fmicb.2024.1390722 -
BMC Microbiology Sep 2023The coexistence of hypertension and type 2 diabetes mellitus (T2DM) may largely increase the risk for cardiovascular disease. However, there is no clear consensus on the...
BACKGROUND
The coexistence of hypertension and type 2 diabetes mellitus (T2DM) may largely increase the risk for cardiovascular disease. However, there is no clear consensus on the association between hypertension and the risk of diabetes. Gut microbiota plays important roles in the development of hypertension and T2DM, but whether there is difference between hypertension patients with or without T2DM has not been explored yet.
METHODS
We recruited 101 hypertension patients in this study (72 patients without T2DM named HT group and 29 patients with T2DM named HT-T2DM group). Their blood samples were collected for testing clinical characteristics and fecal samples were tested for bacterial DNA using 16 S ribosomal RNA gene sequencing targeting the V3 and V4 region. The data of 40 samples were downloaded from project PRJNA815750 as health control (HC group) in this study. The community composition and structure of the microbiome, taxonomic difference, co-occurrence network and functional enrichment were analyzed by alpha/beta diversity, LEfSe, Fruchterman Reingold's algorithm and PICRUSt2 functional analysis, respectively.
RESULTS
Alpha and beta diversity analysis showed significant differences in microbial community richness and composition among the three groups. The HC group had a significantly higher Simpson index and a distinct microbiota community compared to the HT and HT-T2DM groups, as demonstrated by significant differences in unweighted and weighted UniFrac distances. The LEfSe analysis identified specific taxa that had significantly different abundance among the groups, such as Bacteroides uniformis, Blautia wexlerae, Alistipes putredinis, and Prevotella stercorea in the HC group, Prevotella copri and Phascolarctobacterium faecium in the HT group, and Klebsiella pneumoniae in the HT-T2DM group. Co-occurrence network analysis indicates that Prevotella copri, Mediterraneibacter gnavus, Alistipes onderdonkii and some unidentified species act as key nodes in the network. Differentially functional pathway identified by PICRUSt2 were concentrated in nutrition and energy metabolism, as well as the biosynthesis of other secondary metabolites.
CONCLUSIONS
Our study found significant differences in microbial community richness, composition, and function among the healthy controls, hypertension patients with and without T2DM. Some specific taxa may explain this difference and serve as potential therapeutic targets for hypertension, T2DM, and their coexistence.
Topics: Humans; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; East Asian People; Hypertension
PubMed: 37689641
DOI: 10.1186/s12866-023-02967-x -
Microbiome Jul 2023Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant...
BACKGROUND
Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (V ), the within-individual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced V could effectively shift gut microbiome composition; reshape the inflammatory response, triglyceride, and cholesterol levels; and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the V of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n = 36) and high (n = 34) V of LS. Partial least square-discriminant analysis and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations.
RESULTS
We identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the V rabbit populations of over than 80%. Compared to the high V population, the low V (resilient) population was characterized by an underrepresentation of Megasphaera sp., Acetatifactor muris, Bacteroidetes rodentium, Ruminococcus bromii, Bacteroidetes togonis, and Eggerthella sp. and greater abundances of Alistipes shahii, Alistipes putredinis, Odoribacter splanchnicus, Limosilactobacillus fermentum, and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience.
CONCLUSIONS
This is the first study to show that selection for V of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the V rabbit populations. Video Abstract.
Topics: Animals; Rabbits; Gastrointestinal Microbiome; Feces; Microbiota; Phenotype; Metagenome
PubMed: 37400907
DOI: 10.1186/s40168-023-01580-4 -
Liver International : Official Journal... May 2024Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and...
BACKGROUND AND AIMS
Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients.
METHODS
113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4.
RESULTS
We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV.
CONCLUSIONS
In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Escherichia coli; Liver; Fibrosis; Bariatric Surgery; Metabolome; Glycerophospholipids; Glucose; Obesity, Morbid
PubMed: 38353022
DOI: 10.1111/liv.15864 -
Nutrients Apr 2024Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in...
Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of , , , sp000434735, and were more enriched in the ZD group, while probiotic bacteria showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.
Topics: Humans; Gastrointestinal Microbiome; Zinc; Child; Male; Female; Feces; Bacteria; Intestinal Mucosa; Metabolome; Intestines
PubMed: 38732540
DOI: 10.3390/nu16091289 -
Chinese Journal of Cancer Research =... Aug 2023The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases...
OBJECTIVE
The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT).
METHODS
A total of 108 patients with various hematological disorders were selected from Peking University People's Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.
RESULTS
After HSCT, significant decreases in calf circumference and body mass index (BMI) were observed, accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of , , and species before and after HSCT (P<0.05). Before HSCT, sarcopenic patients had lower levels and higher levels than non-sarcopenia patients (P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the post-HSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre- and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size (LEfSe) identified , , , and as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups (P<0.05).
CONCLUSIONS
This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.
PubMed: 37691890
DOI: 10.21147/j.issn.1000-9604.2023.04.05 -
Inflammatory Bowel Diseases May 2024The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal...
BACKGROUND
The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.
METHODS
Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies.
RESULTS
Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling.
CONCLUSIONS
This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.
PubMed: 38733623
DOI: 10.1093/ibd/izae080 -
European Journal of Immunology May 2024HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist,...
HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist, vesatolimod, was previously associated with a modest delay in viral rebound following analytical treatment interruption in HIV controllers (HCs). Using a retrospective analysis of fecal samples from HCs treated with vesatolimod or placebo (NCT03060447), people with chronic HIV (CH; NCT02858401) or without HIV (PWOH), we examined fecal microbiome profile in HCs before/after treatment, and in CH and PWOH. Microbiome diversity and abundance were compared between groups to investigate the association between specific phyla/species, immune biomarkers, and viral outcomes during treatment interruption. Although there were no significant differences in gut microbiome diversity between people with and without HIV, HCs, and CH shared common features that distinguished them from PWOH. there was a trend toward greater microbiome diversity among HCs. Treatment with vesatolimod reduced dysbiosis in HCs. Firmicutes positively correlated with T-cell activation, while Bacteroidetes and Euryarchaeota inversely correlated with TLR7-mediated immune activation. Specific types of fecal microbiome abundance (e.g. Alistipes putredinis) positively correlated with HIV rebound. In conclusion, variability in the composition of the fecal microbiome is associated with markers of immune activation following vesatolimod treatment and ART interruption.
PubMed: 38727191
DOI: 10.1002/eji.202350809