Gut microbiota BMJ Changes in the gut microbiota gastroenterology composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy Hidetaka Yanagi, Ayumi Tsuda, Masashi Matsushima, Shunsuke Takahashi Genki Ozawa, Yasuhiro Koga, Atsushi Takagi To cite: Yanagi H, Tsuda A, ABSTRACT Matsushima M. et al bjective To investigate the influence of antimicrobials on Summary box 3o9N9=N8 omposition and the plasma level using Helicobacter pylori-infected patients who What is already known about this subject? underwent eradication thera Gut microbiota plays a fundamental role in the elicobacter pylori-infected Design Twenty H pylori-infected patients(mean age 68.3 pathophysiology of obesity atients with eradication therapy. BM Open Gastro years old) who underwent eradication therapy participated Ghrelin is associated with obesity after the 2017: 4: e000182 do: 10.1136/ in the study. For the therapy, patients had 1 week of eradication of Helicobacter pylori megas-2017-000182 triple therapy consisting of amoxicillin, clarithromycin What are the new findings? and proton-pump inhibitors Stool and blood samples p Alteration in the gut microbiota may affect the 8gNz3 Received 9 october 2017 were obtained before(S1), immediately after(S2) and/ ccepted 8 November 2017 or 3 months after(S3)the therapies. The concentrations of ghrelin and leptin in the blood were assayed using How might it impact on clinical practice in the学 an ELISA. The V3-V4 region of the 16s rRNa gene was foreseeable future? amplified using bacterial DNA from the stool, and about Both the gut microbiota profiling and plasma 50000 high-quality amplicons per sample were grouped ghrelin level might be used as an earliest nto operational taxonomic units for bacteriological biomarker to foresee the insulin resistance or significantly greater at S3 than S1(P<0.01). This increase in the b F ratio between S3 and S1 was found in 15 out tested, route of administration, duration of of 20 patients. a significant decrease in the concentration follor follow-up and so on. However, in the eradi- of active ghrelin(P=0.003)in the plasma was observed cation therapy of Helicobacter pylori, the first- g etween $3 and s1. There was a statistically significant line therapy has been widely used, which correlation between the rate of patients whose B: F ratio consists of oral administration of clarithro- Check for updates increased and that of patients whose active ghrelin level epartment of Genera decreased between S3 and S1 according to Fisher's exact .ycin, amoxicillin and a proton-pump inhib- Q robability test(P=0.03) itor twice a day for 7 days. Therefore, it will 4 Medicine, Tokai University School of medicine. Isehara Conclusions Changes in the gut microbiota, such as the B: F ratio after treatment with antimicrobials, might cause to use H. pylorHinfected patients with erad- a change in the plasma ghrelin level, as the direct and ication therapy as subjects in the study of 8 Gastroenterology, Tokai earliest target of antimicrobials would be the microbiota the effect of antimicrobials on indigenous University School of Medicine, rather than the hormone-secreting system. bacteria in human hara, Japa It was reported that Technical Department, body mass index significantly increased l year Techno Suruga Laboratory Co Ltd, Shizuoka, Japan INTRODUCTION ter the eradication of H. pylori when exam- Laboratory for Infectious Although antimicrobials have definite effects d in 579 Japanese patients. Ghrelin Diseases, Tokai University on particular pathogenic bacteria, the effect a multifunctional hormone that facilitates School of medicine. isehata Japan community and metabolism has recently been ghrelin is predominantly synthesised and explored. Many of those studies performed secreted by the gastric mucosa, the obesity y Dr Yasuhiro Koga so far are characterised by significant hetero- associated with eradication of H. pylori yasuhiro@isicc. u-tokai ac ip geneity with respect to type of antimicrobials has been attributed to an increase in the Yanagi H, et al. BMJ Open Gastro 2017: 4: e000182 doi 10. 1136/bmjgast-2017-000187Yanagi H, et al. BMJ Open Gastro 2017;4:e000182. doi:10.1136/bmjgast-2017-000182 1 Changes in the gut microbiota composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy Hidetaka Yanagi,1 Ayumi Tsuda,1 Masashi Matsushima,2 Shunsuke Takahashi,3 Genki Ozawa,3 Yasuhiro Koga,4 Atsushi Takagi1 To cite: Yanagi H, Tsuda A, Matsushima M, et al. Changes in the gut microbiota composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy. BMJ Open Gastro 2017;4:e000182. doi:10.1136/ bmjgast-2017-000182 Received 9 October 2017 Accepted 8 November 2017 1 Department of General Medicine, Tokai University School of Medicine, Isehara, Japan 2 Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan 3 Technical Department, TechnoSuruga Laboratory Co. Ltd, Shizuoka, Japan 4 Laboratory for Infectious Diseases, Tokai University School of Medicine, Isehata, Japan Correspondence to Dr Yasuhiro Koga; yasuhiro@is.icc.u-tokai.ac.jp Gut microbiota Abstract Objective To investigate the influence of antimicrobials on both the gut microbiota structure and the plasma ghrelin level using Helicobacter pylori-infected patients who underwent eradication therapy. Design Twenty H. pylori-infected patients (mean age 68.3 years old) who underwent eradication therapy participated in the study. For the therapy, patients had 1week of triple therapy consisting of amoxicillin, clarithromycin and proton-pump inhibitors. Stool and blood samples were obtained before (S1), immediately after (S2) and/ or 3 months after (S3) the therapies. The concentrations of ghrelin and leptin in the blood were assayed using an ELISA. The V3-V4 region of the 16S rRNA gene was amplified using bacterial DNA from the stool, and about 50 000 high-quality amplicons per sample were grouped into operational taxonomic units for bacteriological analyses. Results The Bacteroidetes:Firmicutes (B:F) ratio was significantly greater at S3 than S1 (P<0.01). This increase in the B:F ratio between S3 and S1 was found in 15 out of 20 patients. A significant decrease in the concentration of active ghrelin (P=0.003) in the plasma was observed between S3 and S1. There was a statistically significant correlation between the rate of patients whose B:F ratio increased and that of patients whose active ghrelin level decreased between S3 and S1 according to Fisher’s exact probability test (P=0.03). Conclusions Changes in the gut microbiota, such as the B:F ratio after treatment with antimicrobials, might cause a change in the plasma ghrelin level, as the direct and earliest target of antimicrobials would be the microbiota rather than the hormone-secreting system. Introduction Although antimicrobials have definite effects on particular pathogenic bacteria, the effect of antimicrobials on the gut microbial community and metabolism has recently been explored. Many of those studies performed so far are characterised by significant hetero￾geneity with respect to type of antimicrobials tested, route of administration, duration of follow-up and so on. However, in the eradi￾cation therapy of Helicobacter pylori, the first￾line therapy has been widely used, which consists of oral administration of clarithro￾mycin, amoxicillin and a proton-pump inhib￾itor twice a day for 7 days.1 Therefore, it will be free from the problem of heterogeneity to use H. pylori-infected patients with erad￾ication therapy as subjects in the study of the effect of antimicrobials on indigenous bacteria in human. It was reported that the body weight and body mass index significantly increased 1year after the eradication of H. pylori when exam￾ined in 579 Japanese patients.2 Ghrelin is a multifunctional hormone that facilitates fat storage and regulates body weight.3 As ghrelin is predominantly synthesised and secreted by the gastric mucosa, the obesity associated with eradication of H. pylori has been attributed to an increase in the Summary box What is already known about this subject? ► Gut microbiota plays a fundamental role in the pathophysiology of obesity. ► Ghrelin is associated with obesity after the eradication of Helicobacter pylori. What are the new findings? ► Alteration in the gut microbiota may affect the plasma ghrelin level. How might it impact on clinical practice in the foreseeable future? ► Both the gut microbiota profiling and plasma ghrelin level might be used as an earliest biomarker to foresee the insulin resistance or obesity. copyright. on 4 July 2018 by guest. 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