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| {{Uncurated}}
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| =1. Classification=
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| ==a. Higher order taxa==
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| Bacteria; Bacillota; Clostridia; Eubacteriale; Oscillospiraceae; Subdoligranulum
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| =2. Description and significance=
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| Subdoligranulum didolesgii, a Gram-negative anaerobic bacterium is a human gut bacterium that was recently studied in the context of rheumatoid arthritis (RA), a chronic autoimmune condition impacting millions globally [2][3][4]. Named after the Cherokee word for arthritis or rheumatism, S. didolesgii is of interest in the development of RA-related autoimmunity [5]. Emerging evidence suggests that RA may initiate in mucosal tissues, potentially due to infectious agents or immune reactions to antigens, including those produced by S. didolesgii[5][6]. Previously, studies had shown that Subdoligranulum species? are associated with health benefits such as improved metabolic markers and gut integrity, making them a potential target for therapeutic interventions in metabolic disorders [7][8]. However, new research indicates that S.didolesgii can influence the immune system and inflammatory responses [2][9][10].
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| =3. Genome structure=
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| The genome of Subdoligranulum sp. Isolate_7 sample (which was later coined S. didolesgii) is 1.7 billion DNA base pairs [11][2] and has a GC content of the genus Subdoligranulum is known 1.7 billion DNA base pairs [11][2] and has a GC content of the genus Subdoligranulum is known [12].
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| S. didolesgii is one of the unclassified species from the genus Subdoligranulum, which is known to be a genus of firmicute in the family Oscillospiraceae [1]. However, S. didolesgii it is also closely linked to both the Ruminococcaceae and Lachnospiraceae families. It suggests a potential resemblance in genome structure to taxa from either family. S. didolesgii’s similarilty to the Ruminococcacae and Lachnospiraceae may be due to their engagement in lateral gene transfer or infection by bacteriophages which leads to the expression of distinct proteins and gain of functions that could lead to host immunomodulation [2].
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| =4. Cell structure=
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| S. didolesgii is a non-spore-forming and Gram-negative staining bacterium [7]. Species in the genus Subdoligranulum tend to exhibit the shape of coccoid-droplet and are highly pleomorphic, along with being non-motile [12]. However, it is uncertain whether S.didolesgii also has the cocci-shaped cell. Since experiments on S.didolesgii species are still ongoing, additional aspects of its the cell structure are yet to be determined.
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| =5. Metabolic processes=
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| Subdoligranulum can hydrolyse esculin but not starch. As a strictly anaerobic organism, S. didolesgii produces butyric and lactic acids with limited acetic and succinct acids as the major end products of glucose metabolism [7][12]. According to the AN-MicroLogTM system, S.didolesgii can utilize a wide range of carbohydrate substrates, which includes N-acetyl-dglucosamine, N-acetyl-d-mannosamine, amygdalin, arbutin, d-cellobiose, dextrin, d-fructose, etc [12]. The API Rapid ID 32A kit does detect activities of α-galactosidase, β-galactosidase, βglucosidase, β-glucuronidase, arginine arylamidase, leucine arylamidase and histidine arylamidase, but only weak or negative activity for α-glucosidase [12]. According to the API ZYM test system, S. variabile has similar positive reactions for α-galactosidase, β-galactosidase,β-glucosidase, β-glucuronidase, but a weak reaction for α-glucosidase [12].
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| =6. Ecology=
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| Currently S. didolesgi (Subdoligranulum didolesgii)i has only been found in the intestines of those with and at-risk of RA, but are not found in healthy patients [13]. It is unclear whether S.didolesgii is a commensal organism or a pathobiont and how it interacts with the rest of the microbial community inside of a host [2]. Furthermore, there is a positive association between the prevalence of Subdoligranulum and microbial diversity as well as high-density lipoprotein (HDL) cholesterol levels in humans, while a negative correlation was observed between Subdoligranulum abundance and factors such as body fat mass, adipocyte size, insulin resistance,levels of leptin, insulin, C-reactive protein (CRP), and interleukin-6 (IL-6) [7]
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| =7. Pathology=
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| S. didolegsii (Subdoligranulum didolesgii) bacteria activate specialized immune cells called T-cells in people with RA. While there is no known pathology yet, studies indicate that S.didolesgii could allow antibodies to bypass intestinal walls and spread to joints [2]. The hypothesis proposed by the researchers who identified this previously unknown bacterial species is that Subdoligranulum facilitates the stimulation of mature isolated lymphoid follicles (ILFs) [2]. The linkage between ILF hyperplasia and IgA dysfunction has been found [14]. The risk of autoimmune disease, such as RA, is claimed to be higher with deficient IgA [15][16]. Molecular mimicry between bacterial and host proteins, microbial stimulation of immune pathways, and alterations in metabolite production all provide plausible mechanisms through which S.didolesgii might contribute to RA-related autoimmunity [2][17].
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| =8. Current Research=
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| S. didolesgii (Subdoligranulum didolesgii) is being studied for future therapeutic options given its involvement and association with RA development [2]. Recent studies have found that pulmonary issues can be part of RA and may involve problems like pleuritis, pleural effusion, interstitial lung disease, and rheumatoid nodules [17]. The treatment for these lung nodules isn't clear-cut, and it depends on the individual case, but one potential treatment proposal includes targeting S.didolesgii in patients’ intestines on the premise that the mucosal immune response in the gut will respond to S. didolesgii and trigger a systemic immune response throughout the whole body [2].
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| In 2022, the Melanoma Bridge Congress, held in Naples, Italy, discussed the most recent developments in melanoma research, placing particular emphasis on key topics essential for melanoma prevention, diagnosis, and therapy [18]. In the era of immune checkpoint inhibitors (ICIs), there's a growing focus on what happens after treatment. However, these treatments can also bring about long-lasting side effects, like immune-related adverse events (irAEs), which are side effects caused by the immune system becoming overly active. The pathophysiology of irAEs involves the development of autoimmunity, including the activation of self-reacting T cells and the production of pre-existing auto-reactive antibodies, such as in cases of autoantibodies targeting S. didolesgii-activated T cells seen in RA [18]. More research is needed to understand and manage complications with ICIs, including the risk factors associated with the immune system to determine viability of this treatment using S.didolesgii.
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| =9. References=
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| 1. U.S. National Library of Medicine. (n.d.). Taxonomy browser (Subdoligranulum). National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=292632
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| 2. Chriswell, M. E., Lefferts, A. R., Clay, M. R., Hsu, A. R., Seifert, J., Feser, M. L., ... & Kuhn, K. A. (2022). Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science translational medicine, 14(668). DOI: 10.1126/scitranslmed.abn5166
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| 3. Meehan, C. J., & Beiko, R. G. (2014). A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria, Genome Biology and Evolution, 6(3):703–713. https://doi.org/10.1093/gbe/evu050
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| 4. La Reau, A. J., Meier-Kolthoff, J. P., Suen G. (2016). Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. Microbial Genomics, 2(12):1-13. doi: 10.1099/mgen.0.000099.
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| 5. Holers, V. M., Demoruelle, M. K., Kuhn, K. A., Buckner, J. H., Robinson, W. H., Okamoto, Y., Norris, J. M., & Deane, K. D. (2018). Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nature Reviews Rheumatology, 14(9):542–557. https://doi.org/10.1038/s41584-018-0070-0
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| 6. Kinslow, J. D., Blum, L. K., Deane, K. D., Demoruelle, M. K., Okamoto, Y., Parish, M. C., Kongpachith, S., Lahey, L. J., Norris, J. M., Robinson, W. H., Holers, V. M. (2016). Elevated IgA plasmablast levels in subjects at risk of developing rheumatoid arthritis. Arthritis Rheumatology, 68(10):2372-83. DOI: 10.1002/art.39771
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| 7. Van Hul M., LeRoy T., Prifti E., Dao, M. C., Paquot, A., Zucker, J. D., … & Cani, P. D. (2022). From correlation to causality: the case of Subdoligranulum. Gut Microbes, 12(1):1-13. doi: 10.1080/19490976.2020.1849998
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| 8. Dao, M. C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E. O., Kayser, B. D., Levenez, F., Chilloux, J., Hoyles, L., MICRO-Obes Consortium, Dumas M. E., Rizkala, S. W., Doré, J., Cani, P. D., & Clément, K. (2016). Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut, 65(3):426-436. DOI: 10.1136/gutjnl-2014-308778
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| 9. Bajaj, J. S., Hylemon, P. B., Ridlon, J. M., Heuman, D. M., Daita, K., White, M. B., Monteith, P., Noble, N. A., Sikaroodi, M., & Gillevet, P. M. (2012). Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology, 303(6):G675-G685. https://doi.org/10.1152/ajpgi.00152.2012
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| 10. Koh, J. H., Lee, E. H., Cha, K. H., Pan, C. H., Kim, D., & Kim, W. U. (2023). Factors associated with the composition of the gut microbiome in patients with established rheumatoid arthritis and its value for predicting treatment responses. Arthritis Research and Therapy, 25(32). https://doi.org/10.1186/s13075-023-03013-x
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| 11. U.S. National Library of Medicine. (n.d.). Paired-end raw read of Subdoligranulum isolate 7 - Sra - NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/sra/SRX13578027
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| 12. Holmstrøm, K., Collins, M. D., Møller, T., Falsen, E., & Lawson, P. A. (2004). Subdoligranulum variabile gen. nov., sp. nov. from human feces. Anaerobe, 10(3):197-203.
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| 13. U.S. Department of Health and Human Services. (2002). Newly discovered species of gut bacteria may cause some cases of rheumatoid arthritis. National Institute of Allergy and Infectious Diseases.
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| 14. Bastlein, C., Burlefinger, R., Holzberg, E., Voeth, C., Garbrecht, M., & Ottenjann, R. (1988). Common variable immunodeficiency syndrome and nodular lymphoid hyperplasia in the small intestine. Endoscopy, 20(5):272–275.
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| 15. Goshen, E., Livne, A., Krupp, M., Hammarstrom, L., Dighiero, G., Slor, H., & Shoenfeld, Y. (1989). Antinuclear and related autoantibodies in sera of healthy subjects with IgA deficiency. Journal of Autoimmunity, 2(1):51–60.
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| 16. Koskinen S. (1996). Long-term follow-up of health in blood donors with primary selective IgA deficiency. Journal of Clinical Immunology, 16(3):165–170.
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| 17. Bektyrganova, S., Kozhakhmet, D., Kim, A., Baigenzhin, A., Togizbayev, G., Doszhan, A., Krivoruchkо, N., Pak, A., Peradze, M., & Sarsengaliyev, T. (2023). A case report of extra‐articular manifestation of rheumatoid arthritis: Rheumatoid nodules in lungs. International Journal of Rheumatic Diseases. DOI: 10.1111/1756-185X.14904
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| 18. Ascierto, P. A., Agarwala, S. S., Warner, A. B., Ernstoff, M. S., Fox, B. A., Gajewski, T. F., Galon, J., Garbe, C., Gastman, B. R., … & Thurin, M. (2023). Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st–3rd, 2022—Naples, Italy). Journal of Translational Medicine, 21(508). https://doi.org/10.1186/s12967-023-04325-x
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