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Scientific Reports Jan 2017Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors...
Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient's intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions.
Topics: Aged; Bacteroides; Case-Control Studies; Female; Gastrointestinal Microbiome; Humans; Macular Degeneration; Male; Middle Aged; Ruminococcus
PubMed: 28094305
DOI: 10.1038/srep40826 -
Viruses Mar 2021Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host....
Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host. Environmental conditions can lead to prophage induction; the switching from prophage replication to lytic replication, that results in new bacteriophage progeny and the lysis of the bacterial host. Despite their abundance in the gut, little is known about what could be inducing these prophages. We show that several medications, at concentrations predicted in the gut, lead to prophage induction of bacterial isolates from the human gut. We tested five medication classes (non-steroidal anti-inflammatory, chemotherapy, mild analgesic, cardiac, and antibiotic) for antimicrobial activity against eight prophage-carrying human gut bacterial representative isolates in vitro. Seven out of eight bacteria showed signs of growth inhibition in response to at least one medication. All medications led to growth inhibition of at least one bacterial isolate. Prophage induction was confirmed in half of the treatments showing antimicrobial activity. Unlike antibiotics, host-targeted medications led to a species-specific induction of , , and to a lesser extent . These results show how common medication consumption can lead to phage-mediated effects, which in turn would alter the human gut microbiome through increased prophage induction.
Topics: Bacteria; Bacteriophages; Gastrointestinal Microbiome; Humans; Lysogeny; Pharmaceutical Preparations; Virus Activation
PubMed: 33799646
DOI: 10.3390/v13030455 -
BMC Genomics Dec 2022The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations...
BACKGROUND
The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals.
RESULTS
This study proposed a systematic machine learning framework and applied it to 870 human stool metagenomes across five countries to obtain comprehensive regional shared biomarkers and conduct a personalized modulation analysis. In our pipeline, a heterogeneous ensemble feature selection diagram is first developed to determine an optimal subset of biomarkers through the aggregation of multiple techniques. Subsequently, a deep reinforcement learning method was established to alter the targeted composition to the desired healthy target. In this manner, we can realize personalized modulation by counterfactual inference. Consequently, a total of 42 species were identified as regional shared biomarkers, and they showed good performance in distinguishing obese people from the healthy group (area under curve (AUC) =0.85) when demonstrated on validation datasets. In addition, by pooling all counterfactual explanations, we found that Akkermansia muciniphila, Faecalibacterium prausnitzii, Prevotella copri, Bacteroides dorei, Bacteroides eggerthii, Alistipes finegoldii, Alistipes shahii, Eubacterium sp. _CAG_180, and Roseburia hominis may be potential broad-spectrum targets with consistent modulation in the multi-regional obese population.
CONCLUSIONS
This article shows that based on our proposed machine-learning framework, we can obtain more comprehensive and accurate biomarkers and provide modulation analysis for the obese population. Moreover, our machine-learning framework will also be very useful for other researchers to further obtain biomarkers and perform counterfactual modulation analysis in different diseases.
Topics: Humans; Gastrointestinal Microbiome; Obesity; Feces; Biomarkers; Machine Learning
PubMed: 36564713
DOI: 10.1186/s12864-022-09087-2 -
Scientific Reports Oct 2018Gut microbiota and blood neutrophil-to-lymphocyte ratio (NLR) are associated with systemic inflammation; however, data on the association between gut microbiota and NLR...
Gut microbiota and blood neutrophil-to-lymphocyte ratio (NLR) are associated with systemic inflammation; however, data on the association between gut microbiota and NLR are lacking. We investigated the association between gut microbiota and NLR. A total of 1,309 subjects who had available data on NLR and 16 S rRNA sequencing of gut microbiota were included in this study. They were grouped according to NLR quartile (Q) as follows: lower Q (n = 328, <25% of NLR range), middle 2Q (n = 653, ≥25% to <75%) and upper Q (n = 328, ≥75%). The diversity and composition of the human gut microbiota in the groups were calculated. The phylogenetic diversity of gut microbiota in the lower group was significantly higher than in the middle 2Q group (P = 0.040). The beta-diversity was significantly different among the three groups (P = 0.043), between the lower and middle 2Q groups (P = 0.029), and between the lower and upper groups (P = 0.026). Bacteroides eggerthii showed a positive correlation with NLR (q = 0.015). The diversity and composition of the gut microbiome were different between the NLR groups. Particularly, patients with a lower NLR had a greater diversity of gut microbiota.
Topics: Adult; Biomarkers; Cross-Sectional Studies; Gastrointestinal Microbiome; Humans; Leukocyte Count; Lymphocyte Count; Lymphocytes; Middle Aged; Neutrophils; Public Health Surveillance; Retrospective Studies
PubMed: 30375452
DOI: 10.1038/s41598-018-34398-4 -
International Journal of Molecular... Jun 2021We previously demonstrated that flavonoid metabolites inhibit cancer cell proliferation through both CDK-dependent and -independent mechanisms. The existing evidence...
We previously demonstrated that flavonoid metabolites inhibit cancer cell proliferation through both CDK-dependent and -independent mechanisms. The existing evidence suggests that gut microbiota is capable of flavonoid biotransformation to generate bioactive metabolites including 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA), 3,4,5-trihyroxybenzoic acid (3,4,5-THBA) and 3,4-dihydroxyphenylacetic acid (DOPAC). In this study, we screened 94 human gut bacterial species for their ability to biotransform flavonoid quercetin into different metabolites. We demonstrated that five of these species were able to degrade quercetin including , , , and . Additional studies showed that could generate 2,4,6-THBA and 3,4-DHBA from quercetin while generates DOPAC. In addition to the differences in the metabolites produced, we also observed that the kinetics of quercetin degradation was different between and , suggesting that the pathways of degradation are likely different between these strains. Similar to the antiproliferative effects of 2,4,6-THBA and 3,4-DHBA demonstrated previously, DOPAC also inhibited colony formation ex vivo in the HCT-116 colon cancer cell line. Consistent with this, the bacterial culture supernatant of also inhibited colony formation in this cell line. Thus, as and generate metabolites possessing antiproliferative activity, we suggest that these strains have the potential to be developed into probiotics to improve human gut health.
Topics: 3,4-Dihydroxyphenylacetic Acid; Actinobacteria; Antineoplastic Agents; Bacillus; Bacteria; Bacterial Proteins; Bacteroides; Bromobenzoates; Cell Proliferation; Cell Survival; Clostridiales; Eubacterium; Gallic Acid; Gastrointestinal Microbiome; Gene Expression Profiling; Gene Expression Regulation, Bacterial; HCT116 Cells; Humans; Hydroxybenzoates; Phylogeny; Quercetin; Sequence Analysis, RNA
PubMed: 34208885
DOI: 10.3390/ijms22137045 -
Protein Science : a Publication of the... Oct 2014Crystal structures of three members (BACOVA_00364 from Bacteroides ovatus, BACUNI_03039 from Bacteroides uniformis and BACEGG_00036 from Bacteroides eggerthii) of the...
Crystal structures of three members (BACOVA_00364 from Bacteroides ovatus, BACUNI_03039 from Bacteroides uniformis and BACEGG_00036 from Bacteroides eggerthii) of the Pfam domain of unknown function (DUF4488) were determined to 1.95, 1.66, and 1.81 Å resolutions, respectively. The protein structures adopt an eight-stranded, calycin-like, β-barrel fold and bind an endogenous unknown ligand at one end of the β-barrel. The amino acids interacting with the ligand are not conserved in any other protein of known structure with this particular fold. The size and chemical environment of the bound ligand suggest binding or transport of a small polar molecule(s) as a potential function for these proteins. These are the first structural representatives of a newly defined PF14869 (DUF4488) Pfam family.
Topics: Bacterial Proteins; Bacteroides; Binding Sites; Carbohydrate Metabolism; Crystallography, X-Ray; Models, Molecular; Molecular Sequence Data; Protein Structure, Secondary; Sequence Alignment
PubMed: 25044324
DOI: 10.1002/pro.2522 -
International Journal of Molecular... Dec 2020The determinants that mediate the interactions between microRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this study was to...
BACKGROUND
The determinants that mediate the interactions between microRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this study was to investigate possible interactions between circulating microRNAs and gut microbiota composition in obesity.
METHOD
The sample comprised 78 subjects with obesity (cases, body mass index (BMI): 30-40 kg/m) and 25 eutrophic individuals (controls, BMI ≤ 25 kg/m). The expression of 96 microRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels. Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR correction was used for multiple comparison analyses.
RESULTS
A total of 26 circulating microRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p and miR-21-5p) with and BMI levels was evidenced ( = 0.148, = 0.004). Moreover, these microRNAs regulate genes that participate in metabolism-related pathways, including fatty acid degradation, insulin signaling and glycerolipid metabolism.
CONCLUSIONS
This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating microRNAs in relation to obesity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts.
Topics: Bacteroides; Biomarkers; Body Mass Index; Circulating MicroRNA; Gastrointestinal Microbiome; Humans; MicroRNAs; Obesity; Polymerase Chain Reaction
PubMed: 33327530
DOI: 10.3390/ijms21249509 -
PloS One 2018Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently,...
Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently, researchers have reported that, in mouse experiments, altered gut microbe-dependent T cell differentiation occurred in gut associated lymphoid tissues. Here, we investigated whether gut microbe alteration existed, and if so, the alteration affected peripheral T cell differentiation in patients with RP. In an analysis of gut microbiota, we found increased annotated species numbers in RP patients compared with normal individuals. In the RP gut microbiota, we observed several predominant species, namely Veillonella parvula, Bacteroides eggerthii, Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species of which were reported to associate with propionate production in human intestine. Propionate is a short-chain fatty acid and is suggested to associate with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut associated lymphoid tissues. IL10 gene expressions were moderately higher in freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than those of normal individuals. Six hours after the initiation of the cell culture, regardless of the presence and absence of mitogen stimulation, IL10 gene expressions were significantly lower in RP patients than those in normal individuals. It is well known that PBMC of patients with autoimmune and inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest that, in RP patients, continuous stimulation of intestinal T cells by excessive propionate leads to the spontaneous IL10 production and a subsequent refractory period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon activation may associate with inflammatory cytokine production of PBMC and subsequently relate to chondritis in RP patients.
Topics: Cell Differentiation; Female; Gastrointestinal Microbiome; Humans; Interleukin-10; Male; Middle Aged; Polychondritis, Relapsing; Propionates; T-Lymphocytes
PubMed: 30235279
DOI: 10.1371/journal.pone.0203657 -
Journal of Bacteriology Apr 1983Randomly cloned fragments of DNA from Bacteroides thetaiotaomicron were used as hybridization probes for differentiation of B. thetaiotaomicron from closely related...
Randomly cloned fragments of DNA from Bacteroides thetaiotaomicron were used as hybridization probes for differentiation of B. thetaiotaomicron from closely related Bacteroides species. HindIII digestion fragments of DNA from B. thetaiotaomicron (type strain) were inserted into plasmid pBR322 and labeled with [alpha-32P]dCTP by nick translation. These labeled plasmids were screened for hybridization to HindIII digests of chromosomal DNA from type strains of the following human colonic Bacteroides species: B. thetaiotaomicron, Bacteroides ovatus, reference strain 3452-A (formerly part of B. distasonis), Bacteroides uniformis, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides distasonis, Bacteroides eggerthii, and reference strain B5-21 (formerly B. fragilis subsp. a). Two of the five cloned fragments hybridized only to DNA from B. thetaiotaomicron. Each of these two fragments hybridized to the same DNA restriction fragment in five strains of B. thetaiotaomicron other than the strain from which the DNA was cloned. One of the cloned fragments (pBT2) was further tested for specificity by determining its ability to hybridize to DNA from 65 additional strains of colonic Bacteroides.
Topics: Bacteroides; Cloning, Molecular; DNA, Bacterial; Nucleic Acid Hybridization; Plasmids; Species Specificity
PubMed: 6833179
DOI: 10.1128/jb.154.1.287-293.1983 -
European Journal of Clinical... Mar 2023Accumulating evidence has related the gut microbiota to colorectal cancer (CRC). Fusobacterium nucleatum has repeatedly been linked to colorectal tumorigenesis. The aim...
Accumulating evidence has related the gut microbiota to colorectal cancer (CRC). Fusobacterium nucleatum has repeatedly been linked to colorectal tumorigenesis. The aim of this study was to investigate microbial composition in different sampling sites, in order to profile the microbial dynamics with CRC progression. Further, we characterized the tumor-associated F. nucleatum subspecies. Here, we conducted Illumina Miseq next-generation sequencing of the 16S rRNA V4 region in biopsy samples, to investigate microbiota alterations in cancer patients, patients with adenomatous polyp, and healthy controls in Norway. Further, Fusobacterium positive tumor biopsies were subjected to MinION nanopore sequencing of Fusobacterium-specific amplicons to characterize the Fusobacterium species and subspecies. We found enrichment of oral biofilm-associated bacteria, Fusobacterium, Gemella, Parvimonas, Granulicatella, Leptotrichia, Peptostreptococcus, Campylobacter, Selenomonas, Porphyromonas, and Prevotella in cancer patients compared to adenomatous polyp patients and control patients. Higher abundance of amplicon sequence variants (ASVs) classified as Phascolarctobacterium, Bacteroides vulgatus, Bacteroides plebeius, Bacteroides eggerthii, Tyzzerella, Desulfovibrio, Frisingicoccus, Eubacterium coprostanoligenes group, and Lachnospiraceae were identified in cancer and adenomatous polyp patients compared to healthy controls. F. nucleatum ssp. animalis was the dominating subspecies. F. nucleatum ssp. nucleatum, F. nucleatum ssp. vincentii, Fusobacterium pseudoperiodonticum, Fusobacterium necrophorum, and Fusobacterium gonidiaformans were identified in five samples. Several biofilm-associated bacteria were enriched at multiple sites in cancer patients. Another group of bacteria was enriched in both cancer and polyps, suggesting that they may have a role in polyp development and possibly early stages of CRC.
Topics: Humans; RNA, Ribosomal, 16S; Fusobacterium nucleatum; Bacteria; Carcinogenesis; Gastrointestinal Microbiome; Adenomatous Polyps; Colorectal Neoplasms
PubMed: 36703031
DOI: 10.1007/s10096-023-04551-7