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Gut Microbes Nov 2020Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of... (Review)
Review
Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of potentially beneficial microbes to have been recognized are members of the genus , who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of spp. in the gut, have been linked with various human disease states. This review provides an overview of species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.
Topics: Animals; Dysbiosis; Eubacterium; Feces; Gastrointestinal Microbiome; Humans; Phylogeny
PubMed: 32835590
DOI: 10.1080/19490976.2020.1802866 -
Cell Host & Microbe Aug 2022Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role...
Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale. Transfer of E. rectale-deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.
Topics: Animals; Butyrates; Eubacterium; Humans; Inflammation; Mice; Myeloid Differentiation Factor 88; NF-kappa B; Toll-Like Receptor 4
PubMed: 35952646
DOI: 10.1016/j.chom.2022.07.003 -
Nature Communications Jun 2023Large temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on...
Large temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on sarcopenia, a senile disease characterized by loss of muscle mass and function. Here, we demonstrate that higher diurnal temperature range in humans has a positive correlation with the prevalence of sarcopenia. Fluctuated temperature exposure (10-25 °C) accelerates muscle atrophy and dampens exercise performance in mid-aged male mice. Interestingly, fluctuated temperature alters the microbiota composition with increased levels of Parabacteroides_distasonis, Duncaniella_dubosii and decreased levels of Candidatus_Amulumruptor, Roseburia, Eubacterium. Transplantation of fluctuated temperature-shaped microbiota replays the adverse effects on muscle function. Mechanically, we find that altered microbiota increases circulating aminoadipic acid, a lysine degradation product. Aminoadipic acid damages mitochondrial function through inhibiting mitophagy in vitro. And Eubacterium supplementation alleviates muscle atrophy and dysfunction induced by fluctuated temperature. Our results uncover the detrimental impact of fluctuated temperature on muscle function and provide a new clue for gut-muscle axis.
Topics: Humans; Male; Animals; Mice; Middle Aged; Gastrointestinal Microbiome; Sarcopenia; Temperature; Muscular Atrophy; Microbiota; Eubacterium
PubMed: 37311782
DOI: 10.1038/s41467-023-39171-4 -
RNA (New York, N.Y.) Feb 2018Group II introns and non-LTR retrotransposons encode a phylogenetically related family of highly processive reverse transcriptases (RTs) that are essential for mobility...
Group II introns and non-LTR retrotransposons encode a phylogenetically related family of highly processive reverse transcriptases (RTs) that are essential for mobility and persistence of these retroelements. Recent crystallographic studies on members of this RT family have revealed that they are structurally distinct from the retroviral RTs that are typically used in biotechnology. However, quantitative, structure-guided analysis of processivity, efficiency, and accuracy of this alternate RT family has been lacking. Here, we characterize the processivity of a group II intron maturase RT from (), for which high-resolution structural information is available. We find that the maturase RT (MarathonRT) efficiently copies transcripts at least 10 kb in length and displays superior intrinsic RT processivity compared to commercial enzymes such as Superscript IV (SSIV). The elevated processivity of MarathonRT is at least partly mediated by a loop structure in the finger subdomain that acts as a steric guard (the α-loop). Additionally, we find that a positively charged secondary RNA binding site on the surface of the RT diminishes the primer utilization efficiency of the enzyme, and that reengineering of this surface enhances capabilities of the MarathonRT. Finally, using single-molecule sequencing, we show that the error frequency of MarathonRT is comparable to that of other high-performance RTs, such as SSIV, which were tested in parallel. Our results provide a structural framework for understanding the enhanced processivity of retroelement RTs, and they demonstrate the potential for engineering a powerful new generation of RT tools for application in biotechnology and research.
Topics: DNA, Complementary; Eubacterium; Genome, Viral; Hepacivirus; Introns; RNA-Directed DNA Polymerase
PubMed: 29109157
DOI: 10.1261/rna.063479.117 -
Frontiers in Endocrinology 2023Recent studies have indicated a potential correlation between intestinal bacteria and primary ovarian insufficiency (POI). However, the causal relationship between the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have indicated a potential correlation between intestinal bacteria and primary ovarian insufficiency (POI). However, the causal relationship between the gut microbiota (GM) and POI remains unclear.
METHODS
A bidirectional two-sample Mendelian randomization (MR) study was conducted to investigate the relationship between the GM and POI. Data on the GM were based on the MiBioGen consortium's summary statistics from the most comprehensive genome-wide association study meta-analysis to date (n=13,266), and POI data were obtained from the R8 release of the FinnGen consortium, containing a total of 424 cases and 181,796 controls. A variety of analytical methods, including inverse variance weighting, maximum likelihood, MR-Egger, weighted median, and constrained maximum likelihood and model averaging and Bayesian information criterion, were utilized to explore the connection between the GM and POI. The Cochran's Q statistics were used to evaluate the heterogeneity of instrumental variables. The MR-Egger and MR-pleiotropy residual sum and outlier (PRESSO) methods were used to identify the horizontal pleiotropy of instrumental variables. The MR Steiger test was used to evaluate the strength of causal relationships. A reverse MR study was performed to investigate the causal relationship between POI and the targeted GMs which were indicated to have a causal relationship with POI in the forward MR evaluation.
RESULTS
The inverse variance weighted analysis indicated that Eubacterium (hallii group) (odds ratio [OR]=0.49, 95% confidence interval [CI]: 0.26-0.9, P=0.022) and Eubacterium (ventriosum group) (OR=0.51, 95% CI: 0.27-0.97, P=0.04) had protective effects on POI, and Intestinibacter (OR=1.82, 95% CI: 1.04-3.2, P=0.037) and Terrisporobacter (OR=2.47, 95% CI: 1.14-5.36, P=0.022) had detrimental effects on POI. Results of the reverse MR analysis indicated that POI had no significant influence on the four GMs. No significant heterogeneity or horizontal pleiotropy was observed in the performance of the instrumental variables.
CONCLUSION
This bidirectional two-sample MR study revealed a causal link between Eubacterium (hallii group), Eubacterium (ventriosum group), Intestinibacter, and Terrisporobacter and POI. Additional clinical trials are needed to gain a clearer understanding of the beneficial or detrimental effects of the GMs on POI and their mechanisms of action.
Topics: Female; Humans; Gastrointestinal Microbiome; Bayes Theorem; Genome-Wide Association Study; Mendelian Randomization Analysis; Primary Ovarian Insufficiency
PubMed: 37424857
DOI: 10.3389/fendo.2023.1183219 -
Frontiers in Cellular and Infection... 2021Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and...
Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of pre-FMT was positively correlated with high GSRS scores, whereas a decrease in abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).
Topics: Autism Spectrum Disorder; Autistic Disorder; Child; Eubacterium; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans
PubMed: 34737978
DOI: 10.3389/fcimb.2021.759435 -
Cell Host & Microbe Apr 2008We have investigated the interrelationship between diet, gut microbial ecology, and energy balance using a mouse model of obesity produced by consumption of a prototypic... (Comparative Study)
Comparative Study
We have investigated the interrelationship between diet, gut microbial ecology, and energy balance using a mouse model of obesity produced by consumption of a prototypic Western diet. Diet-induced obesity (DIO) produced a bloom in a single uncultured clade within the Mollicutes class of the Firmicutes, which was diminished by subsequent dietary manipulations that limit weight gain. Microbiota transplantation from mice with DIO to lean germ-free recipients promoted greater fat deposition than transplants from lean donors. Metagenomic and biochemical analysis of the gut microbiome together with sequencing and metabolic reconstructions of a related human gut-associated Mollicute (Eubacterium dolichum) revealed features that may provide a competitive advantage to members of the bloom in the Western diet nutrient milieu, including import and processing of simple sugars. Our study illustrates how combining comparative metagenomics with gnotobiotic mouse models and specific dietary manipulations can disclose the niches of previously uncharacterized members of the gut microbiota.
Topics: Animals; Bacteria; Carbohydrate Metabolism; Carbohydrates; Cecum; Diet; Disease Models, Animal; Energy Metabolism; Eubacterium; Fats; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular Sequence Data; Obesity; RNA, Bacterial; RNA, Ribosomal, 16S; Specific Pathogen-Free Organisms; Tenericutes
PubMed: 18407065
DOI: 10.1016/j.chom.2008.02.015 -
Nutrients Sep 2023Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut...
BACKGROUND
Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors.
METHODS
In this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality.
RESULTS
Our study found that family , genus , genus , genus , genus , genus , genus , and genus were related to bladder cancer; genus , genus , genus , genus , and genus were related to prostate cancer; class , class , family , genus , genus , genus , genus , genus , and genus were related to renal cell cancer; family , family , genus , genus , and genus were related to renal pelvis cancer; family , genus , and genus were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable.
CONCLUSIONS
Our study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.
Topics: Male; Humans; Gastrointestinal Microbiome; Testicular Neoplasms; Mendelian Randomization Analysis; Urologic Neoplasms; Kidney Neoplasms; Clostridiaceae; Lactobacillales; Bacteroidetes; Genome-Wide Association Study
PubMed: 37764869
DOI: 10.3390/nu15184086 -
Microbial Cell Factories Jan 2024The genus Eubacterium is quite diverse and includes several acetogenic strains capable of fermenting C1-substrates into valuable products. Especially, Eubacterium...
BACKGROUND
The genus Eubacterium is quite diverse and includes several acetogenic strains capable of fermenting C1-substrates into valuable products. Especially, Eubacterium limosum and closely related strains attract attention not only for their capability to ferment C1 gases and liquids, but also due to their ability to produce butyrate. Apart from its well-elucidated metabolism, E. limosum is also genetically accessible, which makes it an interesting candidate to be an industrial biocatalyst.
RESULTS
In this study, we examined genomic, phylogenetic, and physiologic features of E. limosum and the closest related species E. callanderi as well as E. maltosivorans. We sequenced the genomes of the six Eubacterium strains 'FD' (DSM 3662), 'Marburg' (DSM 3468), '2A' (DSM 2593), '11A' (DSM 2594), 'G14' (DSM 107592), and '32' (DSM 20517) and subsequently compared these with previously available genomes of the E. limosum type strain (DSM 20543) as well as the strains 'B2', 'KIST612', 'YI' (DSM 105863), and 'SA11'. This comparison revealed a close relationship between all eleven Eubacterium strains, forming three distinct clades: E. limosum, E. callanderi, and E. maltosivorans. Moreover, we identified the gene clusters responsible for methanol utilization as well as genes mediating chain elongation in all analyzed strains. Subsequent growth experiments revealed that strains of all three clades can convert methanol and produce acetate, butyrate, and hexanoate via reverse β-oxidation. Additionally, we used a harmonized electroporation protocol and successfully transformed eight of these Eubacterium strains to enable recombinant plasmid-based expression of the gene encoding the fluorescence-activating and absorption shifting tag (FAST). Engineered Eubacterium strains were verified regarding their FAST-mediated fluorescence at a single-cell level using a flow cytometry approach. Eventually, strains 'FD' (DSM 3662), '2A' (DSM 2593), '11A' (DSM 2594), and '32' (DSM 20517) were genetically engineered for the first time.
CONCLUSION
Strains of E. limosum, E. callanderi, and E. maltosivorans are outstanding candidates as biocatalysts for anaerobic C1-substrate conversion into valuable biocommodities. A large variety of strains is genetically accessible using a harmonized electroporation protocol, and FAST can serve as a reliable fluorescent reporter protein to characterize genetically engineered cells. In total eleven strains have been assigned to distinct clades, providing a clear and updated classification. Thus, the description of respective Eubacterium species has been emended, improved, aligned, and is requested to be implemented in respective databases.
Topics: Eubacterium; Metabolic Engineering; Methanol; Phylogeny; Butyrates
PubMed: 38233843
DOI: 10.1186/s12934-024-02301-8 -
Microbiology Spectrum Dec 2022The gut microbiota (GM) is associated with colorectal cancer (CRC) development. However, studies demonstrating the role of GM in CRC are limited to metagenomic analyses....
The gut microbiota (GM) is associated with colorectal cancer (CRC) development. However, studies demonstrating the role of GM in CRC are limited to metagenomic analyses. These studies lack direct evidence proving that the candidate strains are involved in CRC, and isolated probiotics for bacteriotherapy. Therefore, to identify novel GM with anti-CRC activity, we previously isolated gut bacteria from the feces of healthy individuals, screened the isolated GM's anti-CRC activity, and discovered that cell-free supernatants of GM isolates demonstrated antiproliferative activity against CRC cells. Here, our study identified one of them as Eubacterium callanderi and chose it for further study because the genus has been suggested to contribute to various aspects of gut health; however, the functions are unknown. First, we confirmed that cell-free supernatant (EcCFS) exerted antiproliferative activity-by inducing apoptosis and cell cycle arrest-that was dose-dependent and specific to cancer cell lines. Next, we discovered that EcCFS active molecules were heat stable and protease insensitive. High-performance liquid chromatography analysis revealed that EcCFS contained high butyrate concentrations possessing anticancer activity. Additionally, gas chromatography-mass spectrometry analysis of the aqueous phase of ethyl acetate-extracted EcCFS and an antiproliferation assay of the aqueous phase and 4-aminobutanoic acid (GABA) suggested that GABA is a possible anti-CRC agent. Finally, in the CT26 allograft mouse model, oral administration and EcCFS peri-tumoral injection inhibited tumor growth . Therefore, our study reveals that has an anti-CRC effect and suggests that it may be a potential candidate for developing probiotics to control CRC. The gut microbiota has been reported to be involved in colorectal cancer, as suggested by metagenomic analysis. However, metagenomic analysis has limitations, such as bias in the analysis and the absence of bacterial resources for follow-up studies. Therefore, we attempted to discover gut microorganisms that are related to colorectal cancer using the culturomics method. In this study, we discovered that Eubacterium callanderi possesses anti-colorectal cancer activity and , suggesting that could be used in bacteriotherapy for colorectal cancer treatment.
Topics: Animals; Mice; Gastrointestinal Microbiome; Eubacterium; Colorectal Neoplasms; Bacteria
PubMed: 36448791
DOI: 10.1128/spectrum.02531-22