1887

Abstract

is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of . We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed genomes were divided into three major phylogenetic clusters. Pan–core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are (tetracycline-resistance gene, present in 75 strains) and (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of . This study provides new insights for understanding the genomic features and health relevance of , and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.

Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award No. 2022YFA1304103)
    • Principle Award Recipient: ChangLiu
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-07-24
2024-05-20
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References

  1. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T et al. Enterotypes of the human gut microbiome. Nature 2011; 473:174–180 [View Article] [PubMed]
    [Google Scholar]
  2. Tauzin AS, Pereira MR, Van Vliet LD, Colin P-Y, Laville E et al. Investigating host-microbiome interactions by droplet based microfluidics. Microbiome 2020; 8:141 [View Article] [PubMed]
    [Google Scholar]
  3. Liu C, Du M-X, Abuduaini R, Yu H-Y, Li D-H et al. Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank. Microbiome 2021; 9:119 [View Article] [PubMed]
    [Google Scholar]
  4. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59–65 [View Article] [PubMed]
    [Google Scholar]
  5. Sagheddu V, Patrone V, Miragoli F, Puglisi E, Morelli L. Infant early gut colonization by Lachnospiraceae: high frequency of Ruminococcus gnavus. Front Pediatr 2016; 4:57 [View Article] [PubMed]
    [Google Scholar]
  6. Nilsen M, Saunders CM, Angell IL, Arntzen , Carlsen KCL et al. Butyrate levels in the transition from an infant- to an adult-like gut microbiota correlate with bacterial networks associated with Eubacterium rectale and Ruminococcus gnavus. Genes 2020; 11:1245 [View Article] [PubMed]
    [Google Scholar]
  7. Abdugheni R, Wang W, Wang Y, Du M, Liu F et al. Metabolite profiling of human‐originated Lachnospiraceae at the strain level. iMeta 2022; 1:e58 [View Article]
    [Google Scholar]
  8. Moore WEC, Johnson JL, Holdeman LV. Emendation of Bacteroidaceae and Butyrivibrio and descriptions of Desulfomonas gen. nov. and ten new species in the genera Desulfomonas, Butyrivibrio, Eubacterium, Clostridium, and Ruminococcus. Int J Syst Bacteriol 1976; 26:238–252 [View Article]
    [Google Scholar]
  9. Graziani F, Pujol A, Nicoletti C, Dou S, Maresca M et al. Ruminococcus gnavus E1 modulates mucin expression and intestinal glycosylation. J Appl Microbiol 2016; 120:1403–1417 [View Article] [PubMed]
    [Google Scholar]
  10. Crost EH, Le Gall G, Laverde-Gomez JA, Mukhopadhya I, Flint HJ et al. Mechanistic insights into the cross-feeding of Ruminococcus gnavus and Ruminococcus bromii on host and dietary carbohydrates. Front Microbiol 2018; 9:2558 [View Article] [PubMed]
    [Google Scholar]
  11. Wu H, Rebello O, Crost EH, Owen CD, Walpole S et al. Fucosidases from the human gut symbiont Ruminococcus gnavus. Cell Mol Life Sci 2021; 78:675–693 [View Article] [PubMed]
    [Google Scholar]
  12. Taglialegna A. Commensal bacteria fight colorectal cancer. Nat Rev Microbiol 2023; 21:276 [View Article] [PubMed]
    [Google Scholar]
  13. Wu L, Yan Q, Chen F, Cao C, Wang S. Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway. Biomed Pharmacother 2021; 135:111187 [View Article] [PubMed]
    [Google Scholar]
  14. Ahn J-R, Lee S-H, Kim B, Nam MH, Ahn YK et al. Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice. Pediatr Allergy Immunol 2022; 33:e13678 [View Article] [PubMed]
    [Google Scholar]
  15. Titécat M, Wallet F, Vieillard M-H, Courcol RJ, Loïez C. Ruminococcus gnavus: an unusual pathogen in septic arthritis. Anaerobe 2014; 30:159–160 [View Article] [PubMed]
    [Google Scholar]
  16. Hansen SGK, Skov MN, Justesen US. Two cases of Ruminococcus gnavus bacteremia associated with diverticulitis. J Clin Microbiol 2013; 51:1334–1336 [View Article] [PubMed]
    [Google Scholar]
  17. Kim YJ, Kang HY, Han Y, Lee MS, Lee HJ. A bloodstream infection by Ruminococcus gnavus in a patient with a gall bladder perforation. Anaerobe 2017; 47:129–131 [View Article] [PubMed]
    [Google Scholar]
  18. Lozano CP, Wilkens LR, Shvetsov YB, Maskarinec G, Park S-Y et al. Associations of the dietary inflammatory index with total adiposity and ectopic fat through the gut microbiota, LPS, and C-reactive protein in the multiethnic cohort-adiposity phenotype study. Am J Clin Nutr 2022; 115:1344–1356 [View Article] [PubMed]
    [Google Scholar]
  19. Hall AB, Yassour M, Sauk J, Garner A, Jiang X et al. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med 2017; 9:103 [View Article] [PubMed]
    [Google Scholar]
  20. Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci 2019; 116:12672–12677 [View Article] [PubMed]
    [Google Scholar]
  21. Mineharu Y, Nakamura Y, Sato N, Kamata T, Oichi Y et al. Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease. Sci Rep 2022; 12:20244 [View Article] [PubMed]
    [Google Scholar]
  22. Zhai L, Huang C, Ning Z, Zhang Y, Zhuang M et al. Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. Cell Host Microbe 2023; 31:33–44 [View Article] [PubMed]
    [Google Scholar]
  23. Palmas V, Pisanu S, Madau V, Casula E, Deledda A et al. Gut microbiota markers associated with obesity and overweight in Italian adults. Sci Rep 2021; 11:5532 [View Article] [PubMed]
    [Google Scholar]
  24. Abdugheni R, Wang Y-J, Li D-H, Du M-X, Liu C et al. Pararoseburia lenta gen. nov., sp. nov. isolated from human faeces. Int J Syst Evol Microbiol 2022; 72:005371 [View Article] [PubMed]
    [Google Scholar]
  25. Abdugheni R, Li D-H, Wang Y-J, Du M-X, Zhou N et al. Acidaminococcus homini s sp. nov., Amedibacillus hominis sp. nov., Lientehia hominis gen. nov. sp. nov., Merdimmobilis hominis gen. nov. sp. nov., and Paraeggerthella hominis sp. nov., isolated from human faeces. Int J Syst Evol Microbiol 2023; 73:005648 [View Article]
    [Google Scholar]
  26. Parks DH, Imelfort M, Skennerton CT, Hugenholtz P, Tyson GW. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res 2015; 25:1043–1055 [View Article] [PubMed]
    [Google Scholar]
  27. Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2006; 35:D5–D12 [View Article] [PubMed]
    [Google Scholar]
  28. Pritchard L, Glover RH, Humphris S, Elphinstone JG, Toth IK. Genomics and taxonomy in diagnostics for food security: soft-rotting enterobacterial plant pathogens. Anal Methods 2016; 8:12–24 [View Article]
    [Google Scholar]
  29. Richter M, Rosselló-Móra R. Shifting the genomic gold standard for the prokaryotic species definition. Proc Natl Acad Sci 2009; 106:19126–19131 [View Article] [PubMed]
    [Google Scholar]
  30. Kolde R, Kolde MR. Package ‘Pheatmap'. R package 2018; 1:10
    [Google Scholar]
  31. Wickham H. ggplot2: Elegant Graphics for Data Analysis, 2nd edn. Dordrecht, Heidelberg, London, New York: Springer; 2009
  32. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  33. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  34. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article] [PubMed]
    [Google Scholar]
  35. Gupta SK, Padmanabhan BR, Diene SM, Lopez-Rojas R, Kempf M et al. ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes. Antimicrob Agents Chemother 2014; 58:212–220 [View Article] [PubMed]
    [Google Scholar]
  36. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article] [PubMed]
    [Google Scholar]
  37. Chen L, Zheng D, Liu B, Yang J, Jin Q. VFDB 2016: hierarchical and refined dataset for big data analysis – 10 years on. Nucleic Acids Res 2016; 44:D694–D697 [View Article] [PubMed]
    [Google Scholar]
  38. Bonin N, Doster E, Worley H, Pinnell LJ, Bravo JE et al. MEGARes and AMR++, v3.0: an updated comprehensive database of antimicrobial resistance determinants and an improved software pipeline for classification using high-throughput sequencing. Nucleic Acids Res 2023; 51:D744–D752 [View Article] [PubMed]
    [Google Scholar]
  39. Kim M, Oh HS, Park SC, Chun J. Towards a taxonomic coherence between average nucleotide identity and 16S rRNA gene sequence similarity for species demarcation of prokaryotes. Int J Syst Evol Microbiol 2014; 64:346–351 [View Article] [PubMed]
    [Google Scholar]
  40. Meier-Kolthoff JP, Carbasse JS, Peinado-Olarte RL, Göker M. TYGS and LPSN: a database tandem for fast and reliable genome-based classification and nomenclature of prokaryotes. Nucleic Acids Res 2022; 50:D801–D807 [View Article] [PubMed]
    [Google Scholar]
  41. Ammor MS, Flórez AB, Alvarez-Martín P, Margolles A, Mayo B. Analysis of tetracycline resistance tet(W) genes and their flanking sequences in intestinal Bifidobacterium species. J Antimicrob Chemother 2008; 62:688–693 [View Article] [PubMed]
    [Google Scholar]
  42. Baron U, Bujard H. Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. Methods Enzymol 2000; 327:401–421 [View Article] [PubMed]
    [Google Scholar]
  43. Wang N, Hang X, Zhang M, Liu X, Yang H. Analysis of newly detected tetracycline resistance genes and their flanking sequences in human intestinal bifidobacteria. Sci Rep 2017; 7:6267 [View Article] [PubMed]
    [Google Scholar]
  44. Gravey F, Galopin S, Grall N, Auzou M, Andremont A et al. Lincosamide resistance mediated by lnu(C) (L phenotype) in a Streptococcus anginosus clinical isolate. J Antimicrob Chemother 2013; 68:2464–2467 [View Article] [PubMed]
    [Google Scholar]
  45. Horaud T, Le Bouguenec C, Pepper K. Molecular genetics of resistance to macrolides, lincosamides and streptogramin B (MLS) in streptococci. J Antimicrob Chemother 1985; 16:111–135 [View Article] [PubMed]
    [Google Scholar]
  46. Schroeder MR, Stephens DS. Macrolide resistance in Streptococcus pneumoniae. Front Cell Infect Microbiol 2016; 6:98 [View Article]
    [Google Scholar]
  47. Henke MT, Brown EM, Cassilly CD, Vlamakis H, Xavier RJ et al. Capsular polysaccharide correlates with immune response to the human gut microbe Ruminococcus gnavus. Proc Natl Acad Sci 2021; 118:e2007595118 [View Article] [PubMed]
    [Google Scholar]
  48. Liu B, Zheng D, Zhou S, Chen L, Yang J. VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Res 2022; 50:D912–D917 [View Article] [PubMed]
    [Google Scholar]
  49. Smith CJ, Rollins LA, Parker AC. Nucleotide sequence determination and genetic analysis of the Bacteroides plasmid, pBI143. Plasmid 1995; 34:211–222 [View Article] [PubMed]
    [Google Scholar]
  50. Moritz EM, Hergenrother PJ. Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci. Proc Natl Acad Sci 2007; 104:311–316 [View Article] [PubMed]
    [Google Scholar]
  51. Gren C, Spiegelhauer MR, Rotbain EC, Ehmsen BK, Kampmann P et al. Ruminococcus gnavus bacteraemia in a patient with multiple haematological malignancies. Access Microbiol 2019; 1:e000048 [View Article] [PubMed]
    [Google Scholar]
  52. Vacca M, Celano G, Calabrese FM, Portincasa P, Gobbetti M et al. The controversial role of human gut Lachnospiraceae. Microorganisms 2020; 8:573 [View Article] [PubMed]
    [Google Scholar]
  53. Crost EH, Tailford LE, Monestier M, Swarbreck D, Henrissat B et al. The mucin-degradation strategy of Ruminococcus gnavus: the importance of intramolecular trans-sialidases. Gut Microbes 2016; 7:302–312 [View Article] [PubMed]
    [Google Scholar]
  54. Han S, Lu Y, Xie J, Fei Y, Zheng G et al. Probiotic gastrointestinal transit and colonization after oral administration: a long journey. Front Cell Infect Microbiol 2021; 11:609722 [View Article] [PubMed]
    [Google Scholar]
  55. Lee SM, Donaldson GP, Mikulski Z, Boyajian S, Ley K et al. Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 2013; 501:426–429 [View Article] [PubMed]
    [Google Scholar]
  56. Castro-Córdova P, Pizarro-Guajardo M, Romero-Rodríguez A. Editorial: Mechanism of colonization and persistence of gut commensal microbiota and pathogens. Front Cell Infect Microbiol 2023; 13:1176453 [View Article] [PubMed]
    [Google Scholar]
  57. Hossain KS, Amarasena S, Mayengbam S. B vitamins and their roles in gut health. Microorganisms 2022; 10:1168 [View Article] [PubMed]
    [Google Scholar]
  58. Voland L, Le Roy T, Debédat J, Clément K. Gut microbiota and vitamin status in persons with obesity: a key interplay. Obes Rev 2022; 23:e13377 [View Article] [PubMed]
    [Google Scholar]
  59. George SE, Devereux R, James J, Wan Y, Diamond GL et al. Dietary lead modulates the mouse intestinal microbiome: subacute exposure to lead acetate and lead contaminated soil. Ecotoxicol Environ Saf 2023; 249:114430 [View Article] [PubMed]
    [Google Scholar]
  60. Cervera-Tison M, Tailford LE, Fuell C, Bruel L, Sulzenbacher G et al. Functional analysis of family GH36 α-galactosidases from Ruminococcus gnavus E1: insights into the metabolism of a plant oligosaccharide by a human gut symbiont. Appl Environ Microbiol 2012; 78:7720–7732 [View Article] [PubMed]
    [Google Scholar]
  61. Lee J-Y, Arai H, Nakamura Y, Fukiya S, Wada M et al. Contribution of the 7β-hydroxysteroid dehydrogenase from Ruminococcus gnavus N53 to ursodeoxycholic acid formation in the human colon. J Lipid Res 2013; 54:3062–3069 [View Article] [PubMed]
    [Google Scholar]
  62. Zhang Z, Zhang Q, Wang T, Xu N, Lu T et al. Assessment of global health risk of antibiotic resistance genes. Nat Commun 2022; 13:1553 [View Article] [PubMed]
    [Google Scholar]
  63. Diallo M, Simons AD, van der Wal H, Collas F, Houweling-Tan B et al. L-Rhamnose metabolism in Clostridium beijerinckii strain DSM 6423. Appl Environ Microbiol 2019; 85:e02656-18 [View Article] [PubMed]
    [Google Scholar]
  64. Kim J-S, Lee KC, Suh MK, Han K-I, Eom MK et al. Mediterraneibacter butyricigenes sp. nov., a butyrate-producing bacterium isolated from human faeces. J Microbiol 2019; 57:38–44 [View Article] [PubMed]
    [Google Scholar]
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