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BMC Microbiology Apr 2024Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases....
BACKGROUND
Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis.
RESULTS
A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium.
CONCLUSION
Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
Topics: Humans; Stomach Neoplasms; Male; Female; Middle Aged; Gastritis; Feces; Metagenome; Bacteria; Aged; Gastrointestinal Microbiome; Adult
PubMed: 38658841
DOI: 10.1186/s12866-024-03219-2 -
Journal of Clinical Medicine Sep 2022Many studies have reported minor complications and disturbance of the gut microbiota after colonoscopy. Compared with air, carbon dioxide (CO) insufflation could...
BACKGROUND
Many studies have reported minor complications and disturbance of the gut microbiota after colonoscopy. Compared with air, carbon dioxide (CO) insufflation could decrease minor complications, but its impact on gut microbiota remains unknown.
METHODS
Thirty-eight healthy subjects were assessed and twenty were randomized to receive either CO or air insufflation during colonoscopy. Neither the participants nor the staff involved in the follow-up knew which gas was used. Minor complications were assessed using symptom scores. Fecal samples were collected at eight time-points for microbiome analysis by full-length 16S rRNA gene amplicon analysis.
RESULTS
Baseline characteristics were similar in both groups. The recovery of minor complications after colonoscopy was faster in the CO group (the day of the colonoscopy) than in the air group (the day after the colonoscopy). There was no significant reduction in alpha diversity (species richness) of the first stool after colonoscopy in the CO group (115.0 ± 32.81 vs. 97.4 ± 42.31, = 0.28) compared with the air group (123.8 ± 37.25 vs. 84.8 ± 31.67, = 0.04). However, there were no differences in beta diversity between the groups. Linear discriminant analysis effect size (LEfSe) analysis indicated that anaerobic probiotics such as , and were more abundant in the CO group than in the air group within 14 days after colonoscopy. On the contrary, the content of , and was higher in the air group.
CONCLUSIONS
CO is beneficial to gut microbiota homeostasis during colonoscopy in healthy subjects. The effects in patients with different diseases need to be further studied.
PubMed: 36142931
DOI: 10.3390/jcm11185281 -
Microbes and Infection Mar 2022Gut microbiota is believed to play a crucial role in obesity. However, the consistent findings among published studies regarding microbiome-obesity interaction are...
Gut microbiota is believed to play a crucial role in obesity. However, the consistent findings among published studies regarding microbiome-obesity interaction are relatively rare, and one of the underlying causes could be the limited sample size of cohort studies. In order to identify gut microbiota changes between normal-weight individuals and obese individuals, fecal samples along with phenotype information from 2262 Chinese individuals were collected and analyzed. Compared with normal-weight individuals, the obese individuals exhibit lower diversity of species and higher diversity of metabolic pathways. In addition, various machine learning models were employed to quantify the relationship between obesity status and Body mass index (BMI) values, of which support vector machine model achieves best performance with 0.716 classification accuracy and 0.485 R score. In addition to two well-established obesity-associated species, three species that have potential to be obesity-related biomarkers, including Bacteroides caccae, Odoribacter splanchnicus and Roseburia hominis were identified. Further analyses of functional pathways also reveal some enriched pathways in obese individuals. Collectively, our data demonstrates tight relationship between obesity and gut microbiota in a large-scale Chinese population. These findings may provide potential targets for the prevention and treatment of obesity.
Topics: Body Mass Index; Feces; Gastrointestinal Microbiome; Humans; Machine Learning; Obesity
PubMed: 34678464
DOI: 10.1016/j.micinf.2021.104892 -
Nature Communications May 2016Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely...
Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.
Topics: Aerobiosis; Anaerobiosis; Bacteria; Caco-2 Cells; Coculture Techniques; Gastrointestinal Microbiome; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Metabolomics; MicroRNAs; Microfluidics; Models, Biological; Reproducibility of Results
PubMed: 27168102
DOI: 10.1038/ncomms11535 -
Scientific Reports Feb 2016Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we...
Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.
Topics: Adult; Aged; Area Under Curve; Bacteria; Bacteroides; Bifidobacterium pseudocatenulatum; Biomarkers; Butyrates; Case-Control Studies; Cohort Studies; Faecalibacterium prausnitzii; Feces; Female; Gastrointestinal Microbiome; Gout; Humans; Intestinal Mucosa; Male; Middle Aged; Polymerase Chain Reaction; Principal Component Analysis; RNA, Ribosomal, 16S; ROC Curve; Sequence Analysis, DNA; Uric Acid
PubMed: 26852926
DOI: 10.1038/srep20602 -
Journal of Neuroinflammation May 2024The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion,...
BACKGROUND
The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls.
METHODS
The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied.
RESULTS
Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IV biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test).
CONCLUSION
In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.
Topics: Humans; HLA-B27 Antigen; Female; Male; Gastrointestinal Microbiome; Middle Aged; Uveitis, Anterior; Adult; Case-Control Studies; Aged
PubMed: 38715051
DOI: 10.1186/s12974-024-03109-4 -
Scientific Reports Sep 2018Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be...
Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.
Topics: Adult; Algorithms; Arthritis, Rheumatoid; Bacteria; Cytokines; Discriminant Analysis; Humans; Microbiota; Nucleic Acids; Osteoarthritis; Principal Component Analysis; Synovial Fluid; Synovial Membrane
PubMed: 30250232
DOI: 10.1038/s41598-018-32675-w -
Infection and Immunity Oct 2001Commensal enteric bacteria are a required pathogenic factor in inflammatory bowel disease (IBD), but the identity of the pertinent bacterial species is unresolved. Using...
Commensal enteric bacteria are a required pathogenic factor in inflammatory bowel disease (IBD), but the identity of the pertinent bacterial species is unresolved. Using an IBD-associated pANCA monoclonal antibody, a 100-kDa protein was recently characterized from an IBD clinical isolate of Bacteroides caccae (p2Lc3). In this study, consensus oligonucleotides were designed from 100-kDa peptides and used to identify a single-copy gene from the p2Lc3 genome. Sequence analysis of the genomic clone revealed a 2,844-bp (948 amino acid) open reading frame encoding features typical of the TonB-linked outer membrane protein family. This gene, termed ompW, was detected by Southern analysis only in B. caccae and was absent in other species of Bacteroides and gram-negative coliforms. The closest homologues of OmpW included the outer membrane proteins SusC of Bacteroides thetaiotaomicron and RagA of Porphyromonas gingivalis. Recombinant OmpW protein was immunoreactive with the monoclonal antibody, and serum anti-OmpW immunoglobulin A levels were elevated in a Crohn's disease patient subset. These findings suggest that OmpW may be a target of the IBD-associated immune response and reveal its structural relationship to a bacterial virulence factor of P. gingivalis and periodontal disease.
Topics: Amino Acid Sequence; Antibodies, Bacterial; Antibodies, Monoclonal; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacteroides; Cloning, Molecular; Crohn Disease; Genes, Bacterial; Humans; Immunoglobulin Fab Fragments; Membrane Proteins; Molecular Sequence Data; Recombinant Fusion Proteins; Sequence Analysis, DNA; Sequence Homology, Amino Acid
PubMed: 11553542
DOI: 10.1128/IAI.69.10.6044-6054.2001 -
Frontiers in Microbiology 2018Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in...
Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, and to the microbiota of obese adolescents, and , Rikenellaceae, , Barnesiellaceae, and to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.
PubMed: 29922272
DOI: 10.3389/fmicb.2018.01210 -
Frontiers in Molecular Neuroscience 2024Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term...
INTRODUCTION
Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences.
METHODS
Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB.
RESULTS
A remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed . spp., spp., spp., and Ordoribacter spp. were significantly different. Functionally, the genus contributed the highest percentage of RNA sequences in control FMBs followed by the genus as the second highest contributor. In the TBI FMB, the genus contributed the most RNA followed by the genus. and were distinct in the top 10 contributing genera in the TBI FMB while and were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance ( < 0.05, -test) or were detected in >80% of the samples in only one of the cohorts (binary distinction).
DISCUSSION
Functional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.
PubMed: 38544523
DOI: 10.3389/fnmol.2024.1341808