R. gnavus

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(Ruminococcus gnavus imaging via microscope). Image credit: Name or Publication.

Classification

Bacteria (Domain); Bacillota (Phylum); Clostridia (Class); Eubacteriales (Order); Lachnospiraceae (Family); Mediterraneibacter (Genus)

Species

Ruminococcus gnavus Edits: Note: The National Center for Biotechnology Information indicates with brackets [] that this species may need to be reclassified into a new genus: Mediterraneibacter (1) (2). Note: named “gnavus” for its high fermentation activity levels (3). EDIT: Introduction Discovered in 1974, Ruminococcus gnavus is an anaerobic bacterium found in the human gut of healthy individuals (4). R. gnavus has also been linked to disease, as an overabundance of R. gnavus in the gut is associated with the exacerbation of symptoms of Crohn’s disease such as abdominal pain and diarrhea (5). Emerging research also suggests extraintestinal effects caused by the bacterium, such as the onset and progression of mental health disorders (6). Less is known about which specific strains are correlated to disease, and a causal relationship has yet to be established (4). Description and Significance Ruminococcus gnavus is a Gram-positive obligate anaerobe bacterium discovered first in the human gastrointestinal tract. Despite its name it is actually a part of the genus Mediterraneibacter, although retaining its Ruminococcus name for study purposes. R.gnavus is considered a part of the normal human gut microbiome in children and adults. It has been suggested that it has a role in priming the gut microbiota in association with standard weight gain velocity in infants. Ruminococcus gnavus is one of few micorbiota bacterium that persists at a consistent level from infancy to throughout adulthood. Studies have shown that R.gnavus is a key biomarker of health and diseases with certain immune/metabolic properties, making it an important bacterium to understand. Genome Structure Ruminococcus gnavus contains circular chromosomes containing 77 RNA coding genes, 3345 protein coding genes, and 3549191 nucleotides. R.gnavus was found to have a mean genome size of 3.46±0.34 Mbp, with a mean G+C conctent of 42.73±0.33 mol%. R.gnavus' pan-core genome analysis revealed a predicted 28,072 genes, with the core genes making up 3.74% (1051) of that. The function of the majority of its core genes are not known. Edits: Strain ATCC 29149 of R. gnavus was used for initial classification of this species into the Ruminococcus genus. The genome of strain ATCC 29149 consists of 43% G:C, which is similar to that of other species within the genus Ruminococcus (3). The genome size of strain ATCC 29149 was 3.62 Mb (megabases) (2). There are 3744 genes within its genome (2). A number of the genes in its genome are involved in translation (144), transcription (252), and replication (257) (2). Specific to protein-coding, R. gnavus has genes encoding for capsular polysaccharide biosynthesis protein Cps4J and PapX protein (7). Additionally, 282 genes are associated with carbohydrate transport, which offers insight into R. gnavus’s role in carbohydrate metabolism (7). The same strain (ATCC 29149) was used to reclassify R. gnavus to the Mediterraneibacter genus (2). Cell Structure, Metabolism and Life Cycle Ruminococcus are coccoid shaped and have not been found to produce spores (2). They can be motile or nonmotile and possess one to three flagella (3). Visually, the cells are elongated with ends that taper off. The typical dimensions of the cell are 0.9 to 1.1 picometers by 1.1 to 1.4 picometers (3). R. gnavus is also Gram-positive (5). R. gnavus was initially classified into the Ruminococcus genus due to its high levels of growth on fermentable carbohydrates. The microbe is now considered to be anaerobic, experimentally demonstrating little tolerance to oxygen after exposure (8). R. gnavus uses fermentation to produce energy, acetate, and formate (4). Other metabolites of R. gnavus include ethanol and lactate. The R. gnavus strain ATCC 29149 breaks down mucin glycan, a carbohydrate component of the mucus lining of the gut, along with glycans that come from dietary sources (4). Studies have also shown that R. gnavus can use substances produced by Ruminococcus bromii, such as glucose and malto-oligosaccharides, as food and energy sources (9). Secondary metabolites of R. gnavus, including tryptophan decarboxylase, have also been identified in mice models (4). Ecology and Pathogenesis There are a multitude of studies that show a large positive association between Crohn's disease and Ruminococcus gnavus populations. R. gnavus populations skyrocket during flare ups in Crohn's disease patients. R. gnavus produces an inflammatory glucorhamnan polysaccharide that triggers the production of inflammatory cytokines. Patients experiencing Crohn's disease and an increase in R. gnavus experience symptoms such as abdominal pain, diarrhea, and bloody stool. Patients experiencing extreme symptoms may face inflammation of the eyes, skin, and spine. In order to survive and thrive within the human gut, R.gnavus evolved mechanisms to adapt to their environment. These are labeled "microbial colonization factors". Ruminococcus gnavus produce antimicrobial peptides called bacteriocins to inhibit the growth of other potential competitors. It has also evolved to produce a range of carbohydrate-active enzymes, allowing them to metabolize complex carbohydrates. Edits: R. gnavus is a human commensal bacteria (10). A variety of strains are present in the epithelial lining of the gut and respond to environmental changes such as shifts in the microbial population within the gut. Metabolites of R. gnavus modulate gut motility, which affects the passage of products through the gastrointestinal tract (10). R. gnavus has strain-specific methods of producing bacteriocins to kill competing bacteria in the gut and an ability to process complex and dietary carbohydrates (4). Penicillin, meropenem, tetracycline, metronidazole and clindamycin are antibiotics that can work against R. gnavus, as demonstrated in vivo (11). R. gnavus has positive and negative associations with human diseases, both intestinally and extraintestinally. These diseases range from inflammatory bowel disease to neurological diseases (4). R. gnavus blooms as symptoms of Crohn’s disease worsen. Inflammatory cytokines produced by R. gnavus may contribute to this relationship (5). Furthermore, R. gnavus may increase oxidative stress, which is often present in patients with inflammatory bowel disease (12). EDIT: Current Research Role in Human Gastrointestinal Disease The current body of research on R. gnavus demonstrates a correlational relationship between R. gnavus and certain diseases like inflammatory bowel disease and Crohn’s disease. Increased levels of R. gnavus were observed alongside adherent and invasive Escherichia coli in patients with Crohn’s disease (13). Additionally, patients with ulcerative colitis that relapsed after fecal microbiota transplantation have a significantly higher amount of R. gnavus in their gut microbiome when compared to patients that stayed in remission (14). Notably, it is unclear whether or not R. gnavus plays a causal role in the development of gastrointestinal diseases like inflammatory bowel disease and Crohn's disease, or if the bacteria benefits from the microbial landscape that is curated by such diseases. Therapeutic Potential While R. gnavus’s negative effects on the gut microbiome are not well-defined, researchers have also begun to investigate the potential for R. gnavus to play a therapeutic role in certain diseases. Primarily, research in this category seeks to further contextualize R. gnavus’s inflammatory effects and polysaccharide production (15). R. gnavus can, too, stimulate T-lymphocyte responses like an antigen by binding directly to immunoglobulin A. Through such mechanisms, R. gnavus can be leveraged to promote health rather than disease in vivo (15). The therapeutic potential of R. gnavus is thought to, also, extend beyond the gut and into the brain through neuroactive secondary metabolites of R. gnavus. Tryptamine, a product of R. gnavus secondary metabolism, assists in the release of serotonin in the brain (4). Thus, an increase of R. gnavus may positively influence serotonin production (6). Serotonin is implicated in several psychiatric and neurological conditions, rendering its metabolism an important area for research on R. gnavus (6). Important to note is that there is no prospective research on R. gnavus that makes use of humans. References Abdugheni, R., Liu, C., Liu, F.-L., Zhou, N., Jiang, C.-Y., Liu, Y., Li, L., Li, W.-J., & Liu, S.-J. (2023, July 24). Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus Gnavus. microbiologyresearch.org. https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.001071 Crost, E. H., Coletto, E., Bell, A., & Juge, N. (2023). Ruminococcus gnavus: Friend or foe for human health. FEMS Microbiology Reviews, 47(2). https://doi.org/10.1093/femsre/fuad014 Henke, M. T., Kenny, D. J., Cassilly, C. D., Vlamakis, H., Xavier, R. J., & Clardy, J. (2019, June 25). ruminococcus gnavus, a member of the human gut microbiome associated with crohn’s disease, produces an inflammatory polysaccharide. Proceedings of the National Academy of Sciences of the United States of America. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601261/ Kegg Genome: Ruminococcus Gnavus. (2020). https://www.genome.jp/kegg-bin/show_organism?org=T06719 Togo, A. H., Diop, A., Bittar, F., Maraninchi, M., Valero, R., Armstrong, N., Dubourg, G., Labas, N., Richez, M., Delerce, J., Levasseur, A., Fournier, P., Raoult, D., & Million, M. (2018). Description of mediterraneibacter massiliensis, gen. nov., sp. nov., a new genus isolated from the gut microbiota of an obese patient and reclassification of ruminococcus faecis, ruminococcus lactaris, ruminococcus torques, ruminococcus gnavus and clostridium glycyrrhizinilyticum as mediterraneibacter faecis comb. nov., mediterraneibacter lactaris comb. nov., mediterraneibacter torques comb. nov., mediterraneibacter gnavus comb. nov. and mediterraneibacter glycyrrhizinilyticus comb. nov. Antonie Van Leeuwenhoek, 111(11), 2107-2128. https://doi.org/10.1007/s10482-018-1104-y Reference Edits (1) Schoch, C. L., Ciufo, S., Domrachev, M., Hotton, C. L., Kannan, S., Khovanskaya, R., Leipe, D., Mcveigh, R., O’Neill, K., Robbertse, B. Sharma, S., Soussov, V., Sullivan, J. P., Sun, L. Turner, S., & Karsch-Mizrachi, I. (2020). NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database (Oxford): baaa062. https://doi.org/10.1093/database/baaa062 (2) Togo, A. H., Diop, A., Bittar, F., Maraninchi, M., Valero, R., Armstrong, N., Dubourg, G., Labas, N., Richez, M., Delerce, J., Levasseur, A., Fournier, P., Raoult, D., & Million, M. (2018). Description of mediterraneibacter massiliensis, gen. nov., sp. nov., a new genus isolated from the gut microbiota of an obese patient and reclassification of ruminococcus faecis, ruminococcus lactaris, ruminococcus torques, ruminococcus gnavus and clostridium glycyrrhizinilyticum as mediterraneibacter faecis comb. nov., mediterraneibacter lactaris comb. nov., mediterraneibacter torques comb. nov., mediterraneibacter gnavus comb. nov. and mediterraneibacter glycyrrhizinilyticus comb. nov. Antonie Van Leeuwenhoek, 111(11), 2107-2128. https://doi.org/10.1007/s10482-018-1104-y (3) Moore, W. E, Johnson, J. L., & Holdeman, L. V. (1976). Emendation of Bacteroidaceae and butyrivibrio and descriptions of Desulfomonas gen. nov. and ten new species in the genera Desulfomonas, Butyrivibrio, Eubacterium, Clostridium, and ruminococcus. International Journal of Systematic Bacteriology, 26(2), 238–252. https://doi.org/10.1099/00207713-26-2-238 (4) Crost, E. H., Coletto, E., Bell, A., & Juge, N. (2023). Ruminococcus gnavus: friend or foe for human health. FEMS Microbiol Rev, 47(2). https://doi.org/10.1093/femsre/fuad014 (5) Henke, M. T., Kenny, D. J., Cassilly, C. D., Vlamakis, H., Xavier, R. J., & Clardy, J. (2019). Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A, 116(26),12672-12677. https://doi.org/10.1073/pnas.1904099116 (6) Coletto, E., Latousakis, D., Pontifex, M. G., Crost, E. H., Vaux, L., Perez Santamarina, E., Goldson, A., Brion, A., Hajihosseini, M. K., Vauzour, D., Savva, G. M., & Juge, N. (2022). The role of the mucin-glycan foraging Ruminococcus gnavus in the communication between the gut and the brain. Gut microbes, 14(1), 2073784. https://doi.org/10.1080/19490976.2022.2073784 (7) Abdugheni, R., Liu, C., Liu, F.L., Zhou, N., Jiang, C.Y., Liu, Y., Li, L., Li, W.J., Liu, S.J. (2023). Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus gnavus. Microb Genom, 9(7), mgen001071. https://doi.org/10.1099/mgen.0.001071 (8) Zhai, L., Huang, C., Ning, Z., Zhang Y., Zhuang, M., Yang, W., Wang, X., Wang, J., Zhang, L., Xiao, H., Zhao, L., Asthana, P., Lam, Y. Y., Willis Chow, C. F., Huang, J., Yuan, S., Chan, K. M., Yuan, C., Lau, J. Y., Wong, H. L. X., & Bian, Z. (2023). Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. Cell Host & Microbe, 31(1), 33-44.e5. https://doi.org/10.1016/j.chom.2022.11.006 (9) Crost E. H., Le Gall, G., Laverde-Gomez, J. A., Mukhopadhya, I., Flint, H. J., & Juge, N. (2018). Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates. Front Microbiol, 9, 2558. https://doi.org/10.3389/fmicb.2018.02558 (10) Arevalo, P., VanInsberghe, D., Elsherbini, J., Gore, J., & Polz, M. F. (2019). A Reverse Ecology Approach Based on a Biological Definition of Microbial Populations. Cell, 178(4), 820–834.e14. https://doi.org/10.1016/j.cell.2019.06.033 (11) Gren, C., Spiegelhauer, M. R., Rotbain, E. C., Ehmsen, B. K., Kampmann, P., & Andersen, L. P. (2019) Ruminococcus gnavus bacteraemia in a patient with multiple haematological malignancies. Access Microbiology, 1(8). https://doi.org/10.1099/acmi.0.000048 (12) Hall, A. B., Yassour, M., Sauk, J., Garner, A., Jiang, X., Arthur, T., Lagoudas, G. K., Vatanen, T., Fornelos, N., Wilson, R., Bertha, M., Cohen, M., Garber, J., Khalili, H., Gevers, D., Ananthakrishnan, A. N., Kugathasan, S., Lander, E. S., Blainey, P., Vlamakis, H., Xavier, R. J., & Huttenhower, C. (2017). A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med, 9, 103. https://doi.org/10.1186/s13073-017-0490-5 (13) Buisson, A., Sokol, H., Hammoudi, N., Nancey, S., Treton, X., Nachury, M., Fumery, M., Hébuterne, X., Rodrigues, M., Hugot, J. P., Boschetti, G., Stefanescu, C., Wils, P., Seksik, P., Le Bourhis, L., Bezault, M., Sauvanet, P., Pereira, B., Allez, M., … & Barnich, N. (2023). Role of adherent and invasive Escherichia coli in Crohn's disease: lessons from the postoperative recurrence model. Gut, 72(1), 39–48. https://doi.org/10.1136/gutjnl-2021-325971 (14) ​​Fuentes, S., Rossen, N. G., van der Spek, M. J., Hartman, J. H., Huuskonen, L., Korpela, K., Salojärvi, J., Aalvink, S., de Vos, W. M., D'Haens, G. R., Zoetendal, E. G., & Ponsioen, C. Y. (2017). Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. ISME J, 11(8), 1877-1889. https://doi.org/10.1038/ismej.2017.44 (15) Henke, M. T., Brown, E. M., Cassilly, C. D., Vlamakis, H., Xavier, R. J., & Clardy, J. (2021). Capsular polysaccharide correlates with immune response to the human gut microbe Ruminococcus gnavus. Proc Natl Acad Sci U S A, 118(20), e2007595118. https://doi.org/10.1073/pnas.2007595118\ Author Page authored by Chris Blackwell, student of Prof. Bradley Tolar at UNC Wilmington. Page edited by Olivia Gibson, Olivia Swearingen Ludolph, Samantha Booth, Francesca DiBernardo, Jamie Khans, students of Professor Bhatnager at Boston University.