Skip to main content
Top
Published in: Inflammation 5/2019

01-10-2019 | Chronic Inflammatory Bowel Disease | ORIGINAL ARTICLE

H.pylori Infection Alleviates Acute and Chronic Colitis with the Expansion of Regulatory B Cells in Mice

Authors: Xia Li, Jiang Tan, Feng Zhang, Qian Xue, Ning Wang, Xu Cong, Jingtong Wang

Published in: Inflammation | Issue 5/2019

Login to get access

Abstract

Epidemiological studies showed that there was an inverse relationship between Helicobacter pylori (H. pylori) infection and the incidence of inflammatory bowel diseases (IBD). Our previous research indicated that the regulatory immune responses induced by H. pylori infection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, mice were infected with H. pylori SS1, and then colitis was induced by 3% dextran sulphate sodium (DSS), to investigate the role of the regulatory B cells in the effects of H. pylori infection on acute and chronic colitis. In acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less, the proinflammatory cytokines mRNA expression downregulated in colonic mucosa, and the percentages of CD19+IL-10+Breg cells were higher in the H. pylori/DSS co-treated groups compared with the DSS-treated groups. Our study suggests that H. pylori infection can alleviate the acute and chronic colitis induced by DSS, and CD19+IL-10+Breg cells may play a critical role in the alleviation of acute and chronic colitis following H. pylori infection.
Literature
1.
go back to reference Cadamuro, A.C., A.F. Rossi, N.M. Maniezzo, and A.E. Silva. 2014. Helicobacter pylori infection: host immune response, implications on gene expression and microRNAs. World Journal of Gastroenterology 20: 1424–1437.CrossRefPubMedPubMedCentral Cadamuro, A.C., A.F. Rossi, N.M. Maniezzo, and A.E. Silva. 2014. Helicobacter pylori infection: host immune response, implications on gene expression and microRNAs. World Journal of Gastroenterology 20: 1424–1437.CrossRefPubMedPubMedCentral
2.
go back to reference Rad, R., L. Brenner, S. Bauer, S. Schwendy, L. Layland, C.P. da Costa, W. Reindl, A. Dossumbekova, M. Friedrich, D. Saur, H. Wagner, R.M. Schmid, and C. Prinz. 2006. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology 131: 525–537.CrossRefPubMed Rad, R., L. Brenner, S. Bauer, S. Schwendy, L. Layland, C.P. da Costa, W. Reindl, A. Dossumbekova, M. Friedrich, D. Saur, H. Wagner, R.M. Schmid, and C. Prinz. 2006. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology 131: 525–537.CrossRefPubMed
3.
go back to reference Kuipers, E.J., and P. Michetti. 2005. Bacteria and mucosal inflammation of the gut: lessons from Helicobacter pylori. Helicobacter 10: 66–70.CrossRefPubMed Kuipers, E.J., and P. Michetti. 2005. Bacteria and mucosal inflammation of the gut: lessons from Helicobacter pylori. Helicobacter 10: 66–70.CrossRefPubMed
4.
go back to reference D'Elios, M.M., and S.J. Czinn. 2014. Immunity, inflammation, and vaccines for Helicobacter pylori. Helicobacter 19 (Suppl 1): 19–26.CrossRefPubMed D'Elios, M.M., and S.J. Czinn. 2014. Immunity, inflammation, and vaccines for Helicobacter pylori. Helicobacter 19 (Suppl 1): 19–26.CrossRefPubMed
5.
go back to reference Lundgren, A., E. Stromberg, A. Sjoling, C. Lindholm, K. Enarsson, A. Edebo, E. Johnsson, E. Suri-Payer, P. Larsson, A. Rudin, A.M. Svennerholm, and B.S. Lundin. 2005. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infection and Immunity 73: 523–531.CrossRefPubMedPubMedCentral Lundgren, A., E. Stromberg, A. Sjoling, C. Lindholm, K. Enarsson, A. Edebo, E. Johnsson, E. Suri-Payer, P. Larsson, A. Rudin, A.M. Svennerholm, and B.S. Lundin. 2005. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infection and Immunity 73: 523–531.CrossRefPubMedPubMedCentral
6.
go back to reference Wei, L., J. Wang, and Y. Liu. 2014. Prior to Foxp3(+) regulatory T-cell induction, interleukin-10-producing B cells expand after Helicobacter pylori infection. Pathogens Disease 72: 45–54.CrossRefPubMed Wei, L., J. Wang, and Y. Liu. 2014. Prior to Foxp3(+) regulatory T-cell induction, interleukin-10-producing B cells expand after Helicobacter pylori infection. Pathogens Disease 72: 45–54.CrossRefPubMed
7.
go back to reference Kao, J.Y., M. Zhang, M.J. Miller, J.C. Mills, B. Wang, M. Liu, K.A. Eaton, W. Zou, B.E. Berndt, T.S. Cole, T. Takeuchi, S.Y. Owyang, and J. Luther. 2010. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology 138: 1046–1054.CrossRefPubMed Kao, J.Y., M. Zhang, M.J. Miller, J.C. Mills, B. Wang, M. Liu, K.A. Eaton, W. Zou, B.E. Berndt, T.S. Cole, T. Takeuchi, S.Y. Owyang, and J. Luther. 2010. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology 138: 1046–1054.CrossRefPubMed
8.
go back to reference Chang, L.L., S.W. Wang, I.C. Wu, F.J. Yu, Y.C. Su, Y.P. Chen, D.C. Wu, C.H. Kuo, and C.H. Hung. 2012. Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients. Applied Microbiology and Biotechnology 96: 211–220.CrossRefPubMedPubMedCentral Chang, L.L., S.W. Wang, I.C. Wu, F.J. Yu, Y.C. Su, Y.P. Chen, D.C. Wu, C.H. Kuo, and C.H. Hung. 2012. Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients. Applied Microbiology and Biotechnology 96: 211–220.CrossRefPubMedPubMedCentral
9.
go back to reference Wu, Xiaowei, Hongzan Ji, Miaofang Yang, Lin Wu, and F. Wang. 2015. Helicobacter pylori infection and inflammatory bowel disease in Asians: a meta analysis. World Journal of Gastroenterology 21: 4750–4756.CrossRefPubMedPubMedCentral Wu, Xiaowei, Hongzan Ji, Miaofang Yang, Lin Wu, and F. Wang. 2015. Helicobacter pylori infection and inflammatory bowel disease in Asians: a meta analysis. World Journal of Gastroenterology 21: 4750–4756.CrossRefPubMedPubMedCentral
10.
go back to reference Luther, J., M. Dave, P.D. Higgins, and J.Y. Kao. 2010. Association between Helicobacter pylori infection and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Inflammatory Bowel Diseases 16: 1077–1084.CrossRefPubMedPubMedCentral Luther, J., M. Dave, P.D. Higgins, and J.Y. Kao. 2010. Association between Helicobacter pylori infection and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Inflammatory Bowel Diseases 16: 1077–1084.CrossRefPubMedPubMedCentral
11.
go back to reference Reibman, J., M. Marmor, J. Filner, M.E. Fernandez-Beros, L. Rogers, G.I. Perez-Perez, and M.J. Blaser. 2008. Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One 3: e4060.CrossRefPubMedPubMedCentral Reibman, J., M. Marmor, J. Filner, M.E. Fernandez-Beros, L. Rogers, G.I. Perez-Perez, and M.J. Blaser. 2008. Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One 3: e4060.CrossRefPubMedPubMedCentral
12.
go back to reference Zevit, Noam, Ran D. Balicer, Herman Avner Cohen, Dorit Karsh, Yaron Niv, and R. Shamir. 2011. Inverse association between Helicobacter pylori and pediatric asthma in a high prevalence population. Helicobacter 17: 30–35.CrossRef Zevit, Noam, Ran D. Balicer, Herman Avner Cohen, Dorit Karsh, Yaron Niv, and R. Shamir. 2011. Inverse association between Helicobacter pylori and pediatric asthma in a high prevalence population. Helicobacter 17: 30–35.CrossRef
13.
go back to reference Herbarth, O., M. Bauer, G.J. Fritz, P. Herbarth, U. Rolle-Kampczyk, P. Krumbiegel, M. Richter, and T. Richter. 2007. Helicobacter pylori colonisation and eczema. Journal of Epidemiology and Community Health 61: 638–640.CrossRefPubMedPubMedCentral Herbarth, O., M. Bauer, G.J. Fritz, P. Herbarth, U. Rolle-Kampczyk, P. Krumbiegel, M. Richter, and T. Richter. 2007. Helicobacter pylori colonisation and eczema. Journal of Epidemiology and Community Health 61: 638–640.CrossRefPubMedPubMedCentral
14.
go back to reference Dieleman, L.A., M.J. Palmen, H. Akol, E. Bloemena, A.S. Pena, S.G.M. Meuwissen, and E.P.V. Rees. 1998. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clinical and Experimental Immunology 114: 385–391.CrossRefPubMedPubMedCentral Dieleman, L.A., M.J. Palmen, H. Akol, E. Bloemena, A.S. Pena, S.G.M. Meuwissen, and E.P.V. Rees. 1998. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clinical and Experimental Immunology 114: 385–391.CrossRefPubMedPubMedCentral
15.
go back to reference Eastaff-Leung, N., N. Mabarrack, A. Barbour, A. Cummins, and S. Barry. 2010. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. Journal of Clinical Immunology 30: 80–89.CrossRefPubMed Eastaff-Leung, N., N. Mabarrack, A. Barbour, A. Cummins, and S. Barry. 2010. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. Journal of Clinical Immunology 30: 80–89.CrossRefPubMed
16.
go back to reference Higgins, P.D., L.A. Johnson, J. Luther, M. Zhang, K.L. Sauder, L.P. Blanco, and J.Y. Kao. 2011. Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine. Inflammatory Bowel Diseases 17: 1398–1408.CrossRefPubMed Higgins, P.D., L.A. Johnson, J. Luther, M. Zhang, K.L. Sauder, L.P. Blanco, and J.Y. Kao. 2011. Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine. Inflammatory Bowel Diseases 17: 1398–1408.CrossRefPubMed
17.
go back to reference Luther, J., S.Y. Owyang, T. Takeuchi, T.S. Cole, M. Zhang, M. Liu, J. Erb-Downward, J.H. Rubenstein, C.C. Chen, A.V. Pierzchala, J.A. Paul, and J.Y. Kao. 2011. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut 60: 1479–1486.CrossRefPubMedPubMedCentral Luther, J., S.Y. Owyang, T. Takeuchi, T.S. Cole, M. Zhang, M. Liu, J. Erb-Downward, J.H. Rubenstein, C.C. Chen, A.V. Pierzchala, J.A. Paul, and J.Y. Kao. 2011. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut 60: 1479–1486.CrossRefPubMedPubMedCentral
18.
go back to reference Gil, J.H., J.W. Seo, M.S. Cho, J.H. Ahn, and H.Y. Sung. 2014. Role of Treg and TH17 cells of the gastric mucosa in children with Helicobacter pylori gastritis. Journal of Pediatric Gastroenterology and Nutrition 58: 245–251.CrossRefPubMed Gil, J.H., J.W. Seo, M.S. Cho, J.H. Ahn, and H.Y. Sung. 2014. Role of Treg and TH17 cells of the gastric mucosa in children with Helicobacter pylori gastritis. Journal of Pediatric Gastroenterology and Nutrition 58: 245–251.CrossRefPubMed
19.
go back to reference Lv, Q., S.M. Qiao, Y. Xia, C. Shi, Y.F. Xia, G.X. Chou, Z.T. Wang, Y. Dai, and Z.F. Wei. 2015. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. International Immunopharmacology 29: 787–797.CrossRefPubMed Lv, Q., S.M. Qiao, Y. Xia, C. Shi, Y.F. Xia, G.X. Chou, Z.T. Wang, Y. Dai, and Z.F. Wei. 2015. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. International Immunopharmacology 29: 787–797.CrossRefPubMed
20.
go back to reference Ansary, M.M., S. Ishihara, A. Oka, R. Kusunoki, N. Oshima, T. Yuki, K. Kawashima, H. Maegawa, N. Kashiwagi, and Y. Kinoshita. 2014. Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function. Inflammatory Bowel Diseases 20: 2308–2320.CrossRefPubMed Ansary, M.M., S. Ishihara, A. Oka, R. Kusunoki, N. Oshima, T. Yuki, K. Kawashima, H. Maegawa, N. Kashiwagi, and Y. Kinoshita. 2014. Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function. Inflammatory Bowel Diseases 20: 2308–2320.CrossRefPubMed
21.
go back to reference Okayasu, Isao, Shigeru Hatakeyama, Masahiro Yamada, Toshifumi Ohkusa, Yoshio Inagaki, and R. Nakaya. 1990. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98: 694–702.CrossRef Okayasu, Isao, Shigeru Hatakeyama, Masahiro Yamada, Toshifumi Ohkusa, Yoshio Inagaki, and R. Nakaya. 1990. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98: 694–702.CrossRef
22.
go back to reference Sonnenberg, A., and R.M. Genta. 2012. Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 35: 469–476.CrossRef Sonnenberg, A., and R.M. Genta. 2012. Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 35: 469–476.CrossRef
23.
go back to reference Yanaba, K., A. Yoshizaki, Y. Asano, T. Kadono, T.F. Tedder, and S. Sato. 2011. IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model. The American Journal of Pathology 178: 735–743.CrossRefPubMedPubMedCentral Yanaba, K., A. Yoshizaki, Y. Asano, T. Kadono, T.F. Tedder, and S. Sato. 2011. IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model. The American Journal of Pathology 178: 735–743.CrossRefPubMedPubMedCentral
24.
go back to reference Oka, A., S. Ishihara, Y. Mishima, Y. Tada, R. Kusunoki, N. Fukuba, T. Yuki, K. Kawashima, S. Matsumoto, and Y. Kinoshita. 2014. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease. Inflammatory Bowel Diseases 20: 315–328.CrossRefPubMed Oka, A., S. Ishihara, Y. Mishima, Y. Tada, R. Kusunoki, N. Fukuba, T. Yuki, K. Kawashima, S. Matsumoto, and Y. Kinoshita. 2014. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease. Inflammatory Bowel Diseases 20: 315–328.CrossRefPubMed
25.
go back to reference Sattler, S., G.S. Ling, D. Xu, L. Hussaarts, A. Romaine, H. Zhao, L. Fossati-Jimack, T. Malik, H.T. Cook, M. Botto, Y.L. Lau, H.H. Smits, F.Y. Liew, and F.P. Huang. 2014. IL-10-producing regulatory B cells induced by IL-33 (Breg (IL-33)) effectively attenuate mucosal inflammatory responses in the gut. Journal of Autoimmunity 50: 107–122.CrossRefPubMedPubMedCentral Sattler, S., G.S. Ling, D. Xu, L. Hussaarts, A. Romaine, H. Zhao, L. Fossati-Jimack, T. Malik, H.T. Cook, M. Botto, Y.L. Lau, H.H. Smits, F.Y. Liew, and F.P. Huang. 2014. IL-10-producing regulatory B cells induced by IL-33 (Breg (IL-33)) effectively attenuate mucosal inflammatory responses in the gut. Journal of Autoimmunity 50: 107–122.CrossRefPubMedPubMedCentral
26.
go back to reference Yanaba, K., J.D. Bouaziz, K.M. Haas, J.C. Poe, M. Fujimoto, and T.F. Tedder. 2008. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28: 639–650.CrossRefPubMed Yanaba, K., J.D. Bouaziz, K.M. Haas, J.C. Poe, M. Fujimoto, and T.F. Tedder. 2008. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28: 639–650.CrossRefPubMed
27.
go back to reference Rosser, E.C., and C. Mauri. 2015. Regulatory B cells: origin, phenotype, and function. Immunity 42: 607–612.CrossRefPubMed Rosser, E.C., and C. Mauri. 2015. Regulatory B cells: origin, phenotype, and function. Immunity 42: 607–612.CrossRefPubMed
28.
go back to reference Lu, F.T., W. Yang, Y.H. Wang, H.D. Ma, W. Tang, J.B. Yang, L. Li, A.A. Ansari, and Z.X. Lian. 2015. Thymic B cells promote thymus-derived regulatory T cell development and proliferation. Journal of Autoimmunity 61: 62–72.CrossRefPubMed Lu, F.T., W. Yang, Y.H. Wang, H.D. Ma, W. Tang, J.B. Yang, L. Li, A.A. Ansari, and Z.X. Lian. 2015. Thymic B cells promote thymus-derived regulatory T cell development and proliferation. Journal of Autoimmunity 61: 62–72.CrossRefPubMed
29.
go back to reference Ding, Y., Y. Liang, B. Deng, A. Qiao, K. Wu, W. Xiao, and W. Gong. 2014. Induction of TGF-beta and IL-10 production in dendritic cells using astilbin to inhibit dextran sulfate sodium-induced colitis. Biochemical and Biophysical Research Communications 446: 529–534.CrossRefPubMed Ding, Y., Y. Liang, B. Deng, A. Qiao, K. Wu, W. Xiao, and W. Gong. 2014. Induction of TGF-beta and IL-10 production in dendritic cells using astilbin to inhibit dextran sulfate sodium-induced colitis. Biochemical and Biophysical Research Communications 446: 529–534.CrossRefPubMed
30.
go back to reference Reyes, J.L., A. Wang, M.R. Fernando, R. Graepel, G. Leung, N. van Rooijen, M. Sigvardsson, and D.M. McKay. 2015. Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages. Journal of Immunology 194: 364–378.CrossRef Reyes, J.L., A. Wang, M.R. Fernando, R. Graepel, G. Leung, N. van Rooijen, M. Sigvardsson, and D.M. McKay. 2015. Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages. Journal of Immunology 194: 364–378.CrossRef
31.
go back to reference Nagai, S., H. Mimuro, T. Yamada, Y. Baba, K. Moro, T. Nochi, H. Kiyono, T. Suzuki, C. Sasakawa, and S. Koyasu. 2007. Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis. Proceedings of the National Academy of Sciences of the United States of America 104: 8971–8976.CrossRefPubMedPubMedCentral Nagai, S., H. Mimuro, T. Yamada, Y. Baba, K. Moro, T. Nochi, H. Kiyono, T. Suzuki, C. Sasakawa, and S. Koyasu. 2007. Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis. Proceedings of the National Academy of Sciences of the United States of America 104: 8971–8976.CrossRefPubMedPubMedCentral
32.
go back to reference Watanabe, N., K. Kiriya, and T. Chiba. 2008. Small intestine Peyer's patches are major induction sites of the Helicobacter-induced host immune responses. Gastroenterology 134: 642–643.CrossRefPubMed Watanabe, N., K. Kiriya, and T. Chiba. 2008. Small intestine Peyer's patches are major induction sites of the Helicobacter-induced host immune responses. Gastroenterology 134: 642–643.CrossRefPubMed
33.
go back to reference Spahn, Thomas W., Hermann Herbst, Paul D. Rennert, Norbert Lugering, Christian Maaser, Mathias Kraft, Adriano Fontana, Howard L. Weiner, Wolfram Domschke, and T. Kucharzik. 2002. Induction of colitis in mice deficient of Peyer’s patches and mesenteric lymph node is associated with increased disease severity and formation of colonic lymphoid patches. The American Journal of Pathology 161: 2273–2282.CrossRefPubMedPubMedCentral Spahn, Thomas W., Hermann Herbst, Paul D. Rennert, Norbert Lugering, Christian Maaser, Mathias Kraft, Adriano Fontana, Howard L. Weiner, Wolfram Domschke, and T. Kucharzik. 2002. Induction of colitis in mice deficient of Peyer’s patches and mesenteric lymph node is associated with increased disease severity and formation of colonic lymphoid patches. The American Journal of Pathology 161: 2273–2282.CrossRefPubMedPubMedCentral
Metadata
Title
H.pylori Infection Alleviates Acute and Chronic Colitis with the Expansion of Regulatory B Cells in Mice
Authors
Xia Li
Jiang Tan
Feng Zhang
Qian Xue
Ning Wang
Xu Cong
Jingtong Wang
Publication date
01-10-2019
Publisher
Springer US
Published in
Inflammation / Issue 5/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-019-01022-0

Other articles of this Issue 5/2019

Inflammation 5/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine