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Biomedicines May 2024The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on...
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with , , and others, while milder cases were linked to , , , and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.
PubMed: 38790958
DOI: 10.3390/biomedicines12050996 -
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 -
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 -
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 -
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 -
Revista Alergia Mexico (Tecamachalco,... Feb 2024To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA.
OBJECTIVE
To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA.
METHODS
MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement.
RESULTS
69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for (p=0,002), (p=0,009), (p=0,008) and . AS vs ReA there was a difference in favour of AS for (p=0,009), (p=0.006), (p=0.031); (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of (p= 0,0003), (p= 0,026) and (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for (p=0.023), (p=0.030) and (p= 0.003). In anti IL-17, (p= 0.012) was decreased.
CONCLUSIONS
There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.
Topics: Humans; Dysbiosis; Male; Female; Adult; Feces; Gastrointestinal Microbiome; Middle Aged; Prohibitins; Spondylarthritis; Spondylitis, Ankylosing; Arthritis, Psoriatic; Arthritis, Reactive
PubMed: 38683098
DOI: 10.29262/ram.v71i1.1305 -
Scientific Reports Feb 2024Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota...
Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities. This study aims to understand how the microbiome differs between an ethnic majority (the Dutch) and minority (the South-Asian Surinamese (SAS)) group with a lower and higher prevalence of T2DM, respectively. Microbiome data from the Healthy Life in an Urban Setting (HELIUS) cohort were used. Two age- and gender-matched groups were compared: the Dutch (n = 41) and SAS (n = 43). Microbial community compositions were generated via DADA2. Metrics of microbial diversity and similarity between groups were computed. Biomarker analyses were performed to determine discriminating taxa. Bacterial co-occurrence networks were constructed to examine ecological patterns. A tight microbiota cluster was observed in the Dutch women, which overlapped with some of the SAS microbiota. The Dutch gut contained a more interconnected microbial ecology, whereas the SAS network was dispersed, i.e., contained fewer inter-taxonomic correlational relationships. Bacteroides caccae, Butyricicoccus, Alistipes putredinis, Coprococcus comes, Odoribacter splanchnicus, and Lachnospira were enriched in the Dutch gut. Haemophilus, Bifidobacterium, and Anaerostipes hadrus discriminated the SAS gut. All but Lachnospira and certain strains of Haemophilus are known to produce SCFAs. The Dutch gut microbiome was distinguished from the SAS by diverse, differentially abundant SCFA-producing taxa with significant cooperation. The dynamic ecology observed in the Dutch was not detected in the SAS. Among several potential gut microbial biomarkers, Haemophilus parainfluenzae likely best characterizes the ethnic minority group, which is more predisposed to T2DM. The higher prevalence of T2DM in the SAS may be associated with the gut dysbiosis observed.
Topics: Humans; Female; Ethnicity; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Adenosine Deaminase; Minority Groups; Intercellular Signaling Peptides and Proteins; Fatty Acids, Volatile
PubMed: 38403716
DOI: 10.1038/s41598-024-54769-4 -
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 -
Oral Oncology Jan 2024Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut...
OBJECTIVES
Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis.
MATERIALS AND METHODS
Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients.
RESULTS
A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding.
CONCLUSION
Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
Topics: Male; Humans; Female; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mucositis; Prospective Studies; Gastrointestinal Microbiome; Chemoradiotherapy
PubMed: 38006691
DOI: 10.1016/j.oraloncology.2023.106623 -
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