Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice
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Abstract Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptin db/db mice for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and reduced glucose output. We also found that CB0313.1 modulated gut microbiota composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes, reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased butyrate-producing bacteria. Changes in gut microbiota following CB0313.1 treatment were associated with enhanced peroxisome proliferator–activated receptor-γ (PPARγ), insulin signaling molecules and mitochondrial function markers. Together, our study suggests that CB0313.1 may act as a beneficial probiotic for the prevention and treatment of hyperglycemia and associated metabolic dysfunction.
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Bacteria belonging to the Clostridia family contribute to the suppression of pathological autoimmunity.
“Bacteria belonging to the Clostridia family contribute to the suppression of pathological autoimmunity (134, 139–143).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [142]
Several microbial factors have been linked to Alzheimer's disease pathogenesis, and a few studies suggested alteration in the commensal microbiota and pathogenic infections as potential causes of Alzheimer's disease.
“Several microbial factors have been linked to the AD pathogenesis (140, 141), and a few studies suggested alteration in the commensal microbiota and pathogenic infections as potential causes of AD (142).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [142]
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An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · see citing works
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762 · see citing works
Self-citationGut metagenome in European women with normal, impaired and diabetic glucose control
Karlsson, F. H., Tremaroli, V., Nookaew, I., Bergström, G., Behre, C. J., Fagerberg, B., Nielsen, J., & Bäckhed, F. (2013) · Nature · doi:10.1038/nature12198 · Cited by 3,115 · see citing works
Tolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., & Gribble, F. M. (2012) · Diabetes · doi:10.2337/db11-1019 · Cited by 2,404 · see citing works
Butyrate improves insulin sensitivity and increases energy expenditure in mice
Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009) · Diabetes · doi:10.2337/db08-1637 · Cited by 2,204 · see citing works
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
MetaHIT consortium, Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., et al. (2015) · Nature · doi:10.1038/nature15766 · Cited by 2,116 · see citing works
Gut microbiome of the Hadza hunter-gatherers
Schnorr, S. L., Candela, M., Rampelli, S., Centanni, M., Consolandi, C., Basaglia, G., Turroni, S., Biagi, E., Peano, C., Severgnini, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms4654 · Cited by 1,317 · see citing works
Revealing the Bacterial Butyrate Synthesis Pathways by Analyzing (Meta)genomic Data
Vital, M., Howe, A. C., & Tiedje, J. M. (2014) · mBio · doi:10.1128/mbio.00889-14 · Cited by 1,189 · see citing works
Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives
Joossens, M., Huys, G., Cnockaert, M., De Preter, V., Verbeke, K., Rutgeerts, P., Vandamme, P., & Vermeire, S. (2011) · Gut · doi:10.1136/gut.2010.223263 · Cited by 1,063 · see citing works
Li, Z., Yang, S., Lin, H., Huang, J., Watkins, P. A., Moser, A. B., Desimone, C., Song, X.-Y., & Diehl, A. M. (2003) · Hepatology · doi:10.1053/jhep.2003.50048 · Cited by 930 · see citing works
The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis
Stilling, R. M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.011 · Cited by 891 · see citing works
Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion
Yadav, H., Lee, J.-H., Lloyd, J., Walter, P., & Rane, S. G. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.452516 · Cited by 709 · see citing works
Roopchand, D. E., Carmody, R. N., Kuhn, P., Moskal, K., Rojas-Silva, P., Turnbaugh, P. J., & Raskin, I. (2015) · Diabetes · doi:10.2337/db14-1916 · Cited by 678 · see citing works
Colberg (2010) · doi:10.2337/dc10-1548 · Cited by 656 · see citing works
Zhang, X., Zhao, Y., Xu, J., Xue, Z., Zhang, M., Pang, X., Zhang, X., & Zhao, L. (2015) · Scientific Reports · doi:10.1038/srep14405 · Cited by 630 · see citing works
Zhang, X., Zhao, Y., Zhang, M., Pang, X., Xu, J., Kang, C., Li, M., Zhang, C., Zhang, Z., Zhang, Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042529 · Cited by 615 · see citing works
Evans, C. C., LePard, K. J., Kwak, J. W., Stancukas, M. C., Laskowski, S., Dougherty, J., Moulton, L., Glawe, A., Wang, Y., Leone, V., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092193 · Cited by 587 · see citing works
Hansen, C. H. F., Krych, Ł., Nielsen, D. S., Vogensen, F. K., Hansen, L. H., Sørensen, S. J., Buschard, K., & Hansen, A. K. (2012) · Diabetologia · doi:10.1007/s00125-012-2564-7 · Cited by 496 · see citing works
Sato, J., Kanazawa, A., Ikeda, F., Yoshihara, T., Goto, H., Abe, H., Komiya, K., Kawaguchi, M., Shimizu, T., Ogihara, T., et al. (2014) · Diabetes Care · doi:10.2337/dc13-2817 · Cited by 438 · see citing works
Standards of Medical Care in Diabetes—2017 : Summary of Revisions
(2016) · Diabetes Care · doi:10.2337/dc17-s003 · Cited by 425 · see citing works
Xu, J. Y., Lian, F., Zhao, L., Zhao, Y., Chen, X., Zhang, X., Guo, Y., Zhang, C., Zhou, Q., Xue, Z., et al. (2014) · The ISME Journal · doi:10.1038/ismej.2014.177 · Cited by 423 · see citing works
Helminth infection promotes colonization resistance via type 2 immunity
Ramanan, D., Bowcutt, R., Lee, S. C., Tang, M. S., Kurtz, Z. D., Ding, Y., Honda, K., Gause, W. C., Blaser, M. J., Bonneau, R., et al. (2016) · Science · doi:10.1126/science.aaf3229 · Cited by 401 · see citing works
Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment
Nobel, Y. R., Cox, L. M., Kirigin, F. F., Bokulich, N. A., Yamanishi, S., Teitler, I., Chung, J., Sohn, J., Barber, C. M., Goldfarb, D. S., et al. (2015) · Nature Communications · doi:10.1038/ncomms8486 · Cited by 374 · see citing works
Endo, H., Niioka, M., Kobayashi, N., Tanaka, M., & Watanabe, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063388 · Cited by 335 · see citing works
Liu, Z., & Habener, J. F. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706105200 · Cited by 323 · see citing works
Haro, C., Montes-Borrego, M., Rangel-Zúñiga, O. A., Alcala-Diaz, J. F., Gómez-Delgado, F., Pérez‐Martínez, P., Delgado‐Lista, J., Quintana‐Navarro, G. M., Tinahones, F. J., Landa, B. B., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3351 · Cited by 302 · see citing works
The SCFA Receptor GPR43 and Energy Metabolism
Kimura, I., Inoue, D., Hirano, K., & Tsujimoto, G. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00085 · Cited by 299 · see citing works
Sun, J., Furio, L., Mecheri, R., van der Does, A. M., Lundeberg, E., Saveanu, L., Chen, Y., van Endert, P., Agerberth, B., & Diana, J. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.013 · Cited by 292 · see citing works
Self-citationAkkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism
Greer, R. L., Dong, X., de Moraes, A. C. F., Zielke, R. A., Fernandes, G. D. R., Peremyslova, E., Vasquez‐Perez, S., Schoenborn, A. A., Gomes, E. P., Pereira, A. C., et al. (2016) · Nature Communications · doi:10.1038/ncomms13329 · Cited by 277 · see citing works
Duan, F. F., Liu, J. H., & March, J. C. (2015) · Diabetes · doi:10.2337/db14-0635 · Cited by 263 · see citing works
Nylund, L., Nermes, M., Isolauri, E., Salminen, S., de Vos, W. M., & Satokari, R. M. (2014) · Allergy · doi:10.1111/all.12549 · Cited by 254 · see citing works
Louis, P., & Flint, H. J. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.02561-06 · Cited by 192 · see citing works
Xie, Z., Hao, H., Tong, C., Cheng, Y., Liu, J., Pang, Y., Si, Y., Guo, Y., Zang, L., Mu, Y., et al. (2015) · Stem Cells · doi:10.1002/stem.2238 · Cited by 178 · see citing works
A gene-targeted approach to investigate the intestinal butyrate-producing bacterialcommunity
Vital, M., Penton, C. R., Wang, Q., Young, V. B., Antonopoulos, D., Sogin, M. L., Morrison, H. G., Raffals, L. H., Chang, E. B., Huffnagle, G. B., et al. (2013) · Microbiome · doi:10.1186/2049-2618-1-8 · Cited by 163 · see citing works
Targeted mutagenesis of the Clostridium acetobutylicum acetone–butanol–ethanol fermentation pathway
Cooksley, C. M., Zhang, Y., Wang, H., Redl, S., Winzer, K., & Minton, N. P. (2012) · Metabolic Engineering · doi:10.1016/j.ymben.2012.09.001 · Cited by 148 · see citing works
Sun, J., Wang, F., Ling, Z., Yu, X., Chen, W., Li, H., Jin, J., Pang, M., Zhang, H., Yu, J., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.042 · Cited by 147 · see citing works
Self-citationLabbé, A., Ganopolsky, J. G., Martoni, C., Prakash, S., & Jones, M. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115175 · Cited by 144 · see citing works
Ali, A., Velasquez, M. T., Hansen, C. T., Mohamed, A. I., & Bhathena, S. J. (2004) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2004.04.005 · Cited by 128 · see citing works
Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway
Wang, X., He, G., Peng, Y., Zhong, W., Wang, Y., & Zhang, B. (2015) · Scientific Reports · doi:10.1038/srep12676 · Cited by 127 · see citing works
Liu, H., Rocha, C. S., Dandekar, S., & Wan, Y. Y. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.09.022 · Cited by 118 · see citing works
Exercise-related hypoglycemia in diabetes mellitus
Younk, L. M., Mikeladze, M., Tate, D., & Davis, S. N. (2011) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.10.78 · Cited by 114 · see citing works
Kim, S. W., Hooker, J. M., Otto, N., Win, K., Muench, L., Shea, C., Carter, P., King, P., Reid, A. E., Volkow, N. D., et al. (2013) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2013.06.007 · Cited by 104 · see citing works
Nabeshima, A., Yamada, S., Guo, X., Tanimoto, A., Wang, K., Shimajiri, S., Kimura, S., Tasaki, T., Noguchi, H., Kitada, S., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4946 · Cited by 104 · see citing works
Udayappan, S. D., Hartstra, A. V., Dallinga‐Thie, G. M., & Nieuwdorp, M. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12293 · Cited by 101 · see citing works
GLP1-derived nonapeptide GLP1(28–36)amide protects pancreatic β-cells from glucolipotoxicity
Liu, Z., Stanojevic, V., Brindamour, L. J., & Habener, J. F. (2012) · Journal of Endocrinology · doi:10.1530/joe-11-0328 · Cited by 83 · see citing works
Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro
Johnson, L., Walton, G., Psichas, A., Frost, G. S., Gibson, G., & Barraclough, T. G. (2015) · Nutrients · doi:10.3390/nu7064480 · Cited by 67 · see citing works
Therapeutic effects of Clostridium butyricum on experimental colitis induced by oxazolone in rats
Zhang, H., Ding, T. T., Zhao, J., Yang, X., Zhang, H., Zhang, J.-J., & Cui, Y. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1821 · Cited by 56 · see citing works
Self-citationInfluence of whole-wheat consumption on fecal microbial community structure of obese diabetic mice
García-Mazcorro, J. F., Ivanov, I. V., Mills, D. A., & Noratto, G. D. (2016) · PeerJ · doi:10.7717/peerj.1702 · Cited by 49 · see citing works
Exendin-4 upregulates the expression of Wnt-4, a novel regulator of pancreatic β-cell proliferation
Heller, C., Kühn, M. C., Mülders-Opgenoorth, B., Schott, M., Willenberg, H. S., Scherbaum, W. A., & Schinner, S. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00144.2011 · Cited by 32 · see citing works
Frost, G. S., Cai, Z., Raven, M., Otway, D. T., Mushtaq, R., & Johnston, J. D. (2014) · Nutrition and Diabetes · doi:10.1038/nutd.2014.25 · Cited by 30 · see citing works
COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways
Boutant, M., Ramos, O. H. P., Tourrel‐Cuzin, C., Movassat, J., Ilias, A., Vallois, D., Planchais, J., Pégorier, J. P., Schuit, F. C., PETIT, P. X., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030847 · Cited by 28 · see citing works
Bhatta, A., Sangani, R., Kolhe, R., Toque, H., Cain, M., Wong, A., Howie, N., Shinde, R. S., Elsalanty, M., Yao, L., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.12.005 · Cited by 26 · see citing works
Jiang, H., Tong, Y.-X., Yan, D., Jia, S., Östenson, C., & Chen, Z. (2015) · Scientific Reports · doi:10.1038/srep15599 · Cited by 23 · see citing works
Cueno, M. E., Kamio, N., Seki, K., et al. (2015) · Cell Stress and Chaperones · doi:10.1007/s12192-015-0584-1 · Cited by 20 · see citing works
Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites
Liu, D.-Q. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i25.4053 · Cited by 13 · see citing works
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The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
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- Authors
- Jia, L., Li, D., Feng, N., Shamoon, M., Sun, Z., Ding, L., Zhang, H., Chen, W., Sun, J., & Chen, Y. Q.
- Affiliations
- Jiangnan University (CN)
- University of Bremen (DE)
- Corresponding author
- Sun, Jia
- Chen, Yong Q
- Venue
- Scientific Reports
- Published
- 2017-08-01
- Volume
- 7
- Issue
- 1
- Pages
- 7046-7046
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5539151
- OpenAlex
- W2739074006
- Cited by
- 179
- References
- 55
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 21 · 2023: 29 · 2022: 27 · 2021: 26 · 2020: 22 · 2019: 15 · 2018: 6
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- National Natural Science Foundation of China (31570915, 31471128, 2017YFD0400200, 2017-02, 91642114, 31400779)
- Government of Jiangsu Province
- State Key Laboratory of Food Science and Technology
- Fundamental Research Funds for the Central Universities
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- type 2 diabetes, butyrate-producing bacteria, probiotics, gut microbiota, hyperglycemia, glucose tolerance, insulin secretion, glucagon-like peptide-1, Firmicutes/Bacteroidetes ratio, Allobaculum, PPARγ, insulin signaling, mitochondrial function, hepatic glucose production, serum lipids, inflammation
- MeSH terms
- Administration, Oral, Animals, Biological Therapy, Butyrates, Diabetes Mellitus, Type 2, Disease Models, Animal, Mice, Inbred C57BL, Treatment Outcome, Probiotics, Gastrointestinal Tract, Clostridium butyricum
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