Influence of Helicobacter pylori infection in gut microbiota related to nutrition status

• Project/Area Number: 18K07938
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical University (2019-2021); Shiga University of Medical Science (2018)
• Principal Investigator: Sugimoto Mitsushige 東京医科大学, 医学部, 教授 (80397398)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 栄養障害 / 腸内細菌 / グレリン / H. pylori / 除菌治療 / 血液透析 / 脳腸相関 / Helicobacter pylori / Dysbiosis / レプチン / 透析 / dysbiosis / 摂食ペプチドホルモン / 栄養状態

Outline of Final Research Achievements

n patients receiving chronic hemodialysis with protein-energy wasting, status of Helicobacter pylori infection significantly correlates with feeding-related peptide levels (i.e., ghrelin and leptin) and nutritional indicators depending on the gastric environment. In addition, the intervention of H. pylori eradication therapy regulates serum ghrelin levels and this change improves nutritional status in in patients receiving hemodialysis. Therefore, it is considered that H. pylori infection could be a new therapeutic target as a regulator of the nutritional environment in patients with malnutrition.
In this study, we showed that the profile of gut microbiota is clearly different between obese patients and undernourished patients. This observation suggested that H. pylori-related dysbiosis of the gut microbiota increase the risk of developing cardiometabolic disorders and disorders of nutritional environment.

Academic Significance and Societal Importance of the Research Achievements

低栄養状態は高齢者、悪性疾患、神経性無食欲症例などの予後規定因子であるが、本邦における高齢化の進行に伴い低栄養者の割合が増加している。そのため低栄養者の予後の改善には栄養状態に影響を及ぼす因子を解析し、適切な対策を練ることが非常に重要と考えられる。
本検討においてH. pylori菌感染が摂食ペプチド値や腸内細菌のプロファイルに関与することで個々の栄養状態に影響を及ぼすことが明らかとなり、今後この栄養改善効果が実際に予後の改善に直接に繋がるか否かについて動物モデルや臨床的研究で証明することが必要と考えられる。

Research Products

• [Journal Article] Efficacy of high-vision transnasal endoscopy using texture and colour enhancement imaging and narrow-band imaging to evaluate gastritis: a randomized controlled trial (2022)
  • Author(s): Sugimoto M, Kawai Y, Morino Y, Hamada M, Iwata E, Niikura R, Nagata N, Koyama Y, Fukuzawa M, Itoi T, Kawai T
  • Journal Title: Annals of Medicine Volume: 54 Issue: 1 Pages: 1004-1013
  • DOI: 10.1080/07853890.2022.2063372
  • Peer Reviewed / Open Access
• [Journal Article] Association between dyspeptic symptoms and endoscopic findings based on the Kyoto classification of gastritis in Japanese male (2022)
  • Author(s): Takahashi K、Sugimoto M、Kawai Y、Hamada M、Iwata E、Niikura R、Nagata N、Fukuzawa M、Itoi T、Ohtsubo T、Kawai T
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 70 Issue: 1 Pages: 79-85
  • DOI: 10.3164/jcbn.21-79
  • NAID: 130008139102
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on anti­thrombotic therapy: newly developed bleeding prediction application software, SAMURAI model (2022)
  • Author(s): Hakoda A, Takeuchi T, Kojima Y, Fujiwara Y, Naito Y, Fukuda S, Koike T, Sugimoto M, Hamada K, Kobara H, Yoshida N, Inaba T, Nagahara A, Koizumi E, Murakami K, Furuta T, Ogasawara N, Isomoto H, Shibagaki K, Kataoka H, Suzuki H, Higuchi K
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 70 Issue: 2 Pages: 189-196
  • DOI: 10.3164/jcbn.21-136
  • NAID: 130008165944
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Linked color imaging effectively detects the endoscopic atrophic border in transnasal endoscopy (2022)
  • Author(s): Kawai Y, Sugimoto M, Hamada M, Iwata E, Niikiura R, Nagata N, Fukuzawa M, Itoi T, Kawai T
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: -
  • NAID: 130008150361
  • Peer Reviewed
• [Journal Article] Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study (2022)
  • Author(s): Kagawa Y, Fukuzawa M, Sugimoto M, Madarame A, Yamaguchi H, Uchida K, Morise T, Koyama Y, Sugimoto A, Yamauchi Y, Kono S, Naito S, Yamamoto K, Kishimoto Y, Inuyama M, Kawai T, Itoi T
  • Journal Title: Surgical Endoscopy Volume: - Issue: 10 Pages: 7240-7249
  • DOI: 10.1007/s00464-022-09096-y
  • Peer Reviewed / Open Access
• [Journal Article] The degree of mucosal atrophy is associated with post‐endoscopic submucosal dissection bleeding in early gastric cancer (2022)
  • Author(s): Hayashi Y, Hatta W, Tsuji Y, Yoshio T, Kakushima N, Hoteya S, Doyama H, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Sugimoto M, Fujishiro M, Masamune A, Takehara T
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 5 Pages: 870-877
  • DOI: 10.1111/jgh.15793
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of a third-generation high-vision ultrathin endoscope for evaluating gastric atrophy and intestinal metaplasia in Helicobacter pylori-eradicated patients (2022)
  • Author(s): Uematsu J, Sugimoto M, Hamada M, Iwata E, Niikura R, Nagata N, Fukuzawa M, Itoi T, Kawai T
  • Journal Title: Journal Clinical Medicine Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Risk Factors for Bleeding After Endoscopic Submucosal Dissection for Gastric Cancer in Elderly Patients Older Than 80 Years in Japan (2021)
  • Author(s): Sugimoto M, Hatta W, Tsuji Y, Yoshio T, Yabuuchi Y, Hoteya S, Doyama H, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Hayashi Y, Murata M, Fujishiro M, Masamune A, Kawai T
  • Journal Title: Clinical and Translational Gastroenterology Volume: 12 Issue: 9 Pages: e00404-e00404
  • DOI: 10.14309/ctg.0000000000000404
  • NAID: 120007172343
  • Peer Reviewed / Open Access
• [Journal Article] Co-treatment with endoscopic laryngopharyngeal surgery and endoscopic submucosal dissection (2021)
  • Author(s): Yamaguchi H、Sato H、Tsukahara K、Kagawa Y、Okamoto I、Shimizu A、Nagata N、Fukuzawa M、Sugimoto M、Kawai T、Itoi T
  • Journal Title: Auris Nasus Larynx Volume: 48 Issue: 3 Pages: 457-463
  • DOI: 10.1016/j.anl.2020.10.003
  • Peer Reviewed
• [Journal Article] Rebleeding in patients with delayed bleeding after endoscopic submucosal dissection for early gastric cancer (2021)
  • Author(s): Hashimoto M, Hatta W, Tsuji Y, Yoshio T, Yabuuci Y, Hoteya S, Doyama H, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Hayashi Y, Sugimoto M, Fujishiro M, Masamune A, Ohira H
  • Journal Title: Digestive Endoscopy Volume: 33 Issue: 7 Pages: 1120-1130
  • DOI: 10.1111/den.13943
  • Peer Reviewed
• [Journal Article] Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan (2021)
  • Author(s): Shiroma S, Hatta W, Tsuji Y, Yoshio T, Yabuuci Y, Hoteya S, Tsuji S, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Hayashi Y, Sugimoto M, Fujishiro M, Masamune A, Fujisaki J
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 36 Issue: 10 Pages: 2769-2777
  • DOI: 10.1111/jgh.15536
  • Peer Reviewed
• [Journal Article] Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis (2021)
  • Author(s): Morino Y、Sugimoto M、Nagata N、Niikiura R、Iwata E、Hamada M、Kawai Y、Fujimiya T、Takeuchi H、Unezaki S、Kawai T
  • Journal Title: Frontiers in Pharmacology Volume: 12
  • DOI: 10.3389/fphar.2021.759249
  • Peer Reviewed / Open Access
• [Journal Article] Long‐term improvement in constipation‐related symptoms after Helicobacter pylori eradication therapy (2021)
  • Author(s): Murata M、Sugimoto M、Miyamoto S、Kawai T
  • Journal Title: Helicobacter Volume: 27 Issue: 1
  • DOI: 10.1111/hel.12863
  • Peer Reviewed / Open Access
• [Journal Article] Influence of hospital volume on bleeding after endoscopic submucosal dissection for early gastric cancer in Japan: a multicenter propensity score-matched analysis (2021)
  • Author(s): Yabuuchi Y, Hatta W, Tsuji Y, Yoshio T, Kakushima N, Hoteya S, Doyama H, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Hayashi Y, Sugimoto M, Fujishiro M, Masamune A, Ono H
  • Journal Title: Surgical Endoscopy Volume: - Issue: 6 Pages: 4004-4013
  • DOI: 10.1007/s00464-021-08721-6
  • Peer Reviewed / Open Access
• [Journal Article] Treatment strategies for reducing early and late recurrence of colonic diverticular bleeding based on stigmata of recent hemorrhage: a large multicenter study (2021)
  • Author(s): Suguro GM, Nagata N, Kobayashi K, Yamauchi A, Yamada A, Omori J, Ikeya T, Aoyama T, Tominaga N, Sato Y, Kishino T, Ishii N, Sawada T, Murata M, Takao A, Mizukami K, Kinjo K, Fujimori S, Uotani T, Fujita M, Sato H, Suzuki S, Narasaka T, Uemura N, Itawa E, Sugimoto M, Fukuzawa M, Kawai T, Kaise M, Itoi T
  • Journal Title: Gastrointestinal Endoscopy Volume: - Issue: 6 Pages: 1210-1222
  • DOI: 10.1016/j.gie.2021.12.023
  • Peer Reviewed / Open Access
• [Journal Article] Risk of reflux-related symptoms and reflux esophagitis after Helicobacter pylori eradication treatment in the Japanese population (2021)
  • Author(s): Sugimoto M, Murata T, Iwata E, Nagata N, Itoi T, Kawai T
  • Journal Title: J Clin Med Volume: 10 Issue: 7 Pages: 1334-1334
  • DOI: 10.3390/jcm10071434
  • Peer Reviewed / Open Access
• [Journal Article] Cumulative evidence for reducing recurrence of colonic diverticular bleeding using endoscopic clipping versus band ligation: Systematic review and meta-analysis. (2020)
  • Author(s): Nagata N, Niikura R, Ishii N, Kaise M, Omata F, Tominaga N, Kitagawa T, Ikeya T, Kobayashi K, Furumoto Y, Narasaka T, Iwata E, Sugimoto M, Itoi T, Uemura N, Kawai T.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: Epub Issue: 7 Pages: 1738-1743
  • DOI: 10.1111/jgh.15370
  • Peer Reviewed / Open Access
• [Journal Article] Effect of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotype on the outcome of vonoprazan-containing Helicobacter pylori eradication therapy (2020)
  • Author(s): Sugimoto M, Hira D, Murata T, Kawai T, Terada T
  • Journal Title: Antibiotics Volume: 9 Issue: 10 Pages: 645-645
  • DOI: 10.3390/antibiotics9100645
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic reflux esophagitis and reflux-related symptoms after Helicobacter pylori eradication therapy: Meta-analysis (2020)
  • Author(s): Sugimoto M, Murata T, Mizuno H, Iwata E, Nagata N, Itoi T, Kawai T
  • Journal Title: J Clin Med Volume: 9 Issue: 9 Pages: 3007-3007
  • DOI: 10.3390/jcm9093007
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles (2020)
  • Author(s): Murata M, Sugimoto M
  • Journal Title: Eur J Clin Pharmacol Volume: 76 Issue: 9 Pages: 1253-1261
  • DOI: 10.1007/s00228-020-02917-w
  • Peer Reviewed / Open Access
• [Journal Article] Differences in efficacy and safety of lubiprostone used for idiopathic vs. opioid-induced constipation: Meta-analysis of East Asian and Western Populations (2020)
  • Author(s): Sugimoto M, Murata T, Mizuno H
  • Journal Title: J Clin Biochem Nutr Volume: 66 Issue: 15 Pages: 184-192
  • DOI: 10.3748/wjg.v26.i15.1820
  • NAID: 130007839284
  • Peer Reviewed / Open Access
• [Journal Article] Randomised clinical trial: a cross-over study of acid inhibition by vonoprazan 10/20 mg once daily versus rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study) (2020)
  • Author(s): Takeuchi T, Furuta T, Fujiwara Y, Sugimoto M, Kasugai K, Kusano M, Okada H, Suzuk T, Higuchi T, Kagami T, Uotani T, Yamade M, Sawada A, Tanaka F, Harada S, Ota K, Kojima Y, Murata M, Tamura Y, Funaki Y, Kawamura O, Okamoto Y, Fujimoto K, Higuchi K
  • Journal Title: Aliment Pharmacol Ther Volume: ５１ Issue: 5 Pages: 534-543
  • DOI: 10.1111/apt.15641
  • Peer Reviewed
• [Journal Article] Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population: Meta-analysis (2020)
  • Author(s): Sugimoto M, Murata T, Yamaoka Y
  • Journal Title: World J Gastroenterol Volume: 26 Pages: 1820-1840
  • Peer Reviewed
• [Journal Article] Clarithromycin versus metronidazole in first-line Helicobacter pylori triple eradication therapy based on resistance to antimicrobial agents: meta-analysis (2020)
  • Author(s): Murata M, Sugimoto M, Mizuni H, Kanno T, Sato K
  • Journal Title: J Clin Med Volume: 9 Issue: 2 Pages: 543-543
  • DOI: 10.3390/jcm9020543
  • Peer Reviewed
• [Journal Article] Histological analysis of fundic gland polyps enlarged by proton pump inhibitors (2019)
  • Author(s): Fukuda M, Ishigaki H, Sugimoto M, Mukaisho K, Matsubara A, Ishida H, Moritani S, Itoh Y, Sugihara H, Andoh A, Ogasawara K, Murakami K, Kushima R
  • Journal Title: Histopathology Volume: 75 Issue: 4 Pages: 537-545
  • DOI: 10.1111/his.13902
  • Peer Reviewed
• [Journal Article] Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan (2019)
  • Author(s): Sugimoto Mitsushige、Yamaoka Yoshio
  • Journal Title: Frontiers in Pharmacology Volume: 9 Pages: 1560-1560
  • DOI: 10.3389/fphar.2018.01560
  • Peer Reviewed / Open Access
• [Journal Article] Eradication therapy for <i>Helicobacter pylori</i> infection improves nutrition status in Japanese hemodialysis patients: a pilot study (2019)
  • Author(s): Ichikawa H, Sugimoto M, Sakao Y, Sahara S, Ohashi N, Sano K, Tadokoro S, Azekura H, Shimomura A, Yamashita F, Sugiyama D, Fukuta K, Furuta T, Kato A, Sugimoto K, Yasuda H
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 64 Issue: 1 Pages: 91-95
  • DOI: 10.3164/jcbn.18-61
  • NAID: 130007542264
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Gender Differences in Plasma Ghrelin Levels in Hemodialysis Patients (2018)
  • Author(s): Sakao Yukitoshi、Ohashi Naro、Sugimoto Mitsushige、Ichikawa Hitomi、Sahara Shu、Tsuji Takayuki、Kato Akihiko、Fujigaki Yoshihide、Sugimoto Ken、Furuta Takahisa、Yasuda Hideo
  • Journal Title: Therapeutic Apheresis and Dialysis Volume: 23 Issue: 1 Pages: 65-72
  • DOI: 10.1111/1744-9987.12764
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Successful Helicobacter pylori eradication therapy improves symptoms of chronic constipation (2018)
  • Author(s): Murata M, Sugimoto M, Otsuka T, Nishida A, Inatomi O, Bamba S, Andoh A
  • Journal Title: Helicobacter Volume: - Issue: 6
  • DOI: 10.1111/hel.12543
  • Peer Reviewed
• [Presentation] 85歳以上の超高齢者に対する 早期胃癌ESD後出血のリスク因子の検討: 多施設共同研究 (2021)
  • Author(s): 杉本光繁
  • Organizer: JDDW 2021
• [Presentation] H. pylori除菌治療後の逆流性食道炎 発症リスクの検討: メタアナリシス (2021)
  • Author(s): 杉本光繁
  • Organizer: 第27回日本ヘリコバクター学会学術集会
• [Presentation] 酸分泌抑制より考えた三次除菌治療の現状と耐性菌との関係性 (2021)
  • Author(s): 杉本光繁、大塚武人、村田雅樹、永田尚義、河合隆
  • Organizer: 第26回日本ヘリコバクター学会 学術集会
• [Presentation] ボノプラザンを使用したH. pylori除菌治療におけるCYP2C19とCYP3A4/5遺伝子多型の影響 (2020)
  • Author(s): 杉本光繁
  • Organizer: 第41回日本臨床薬理学会学術総会
• [Presentation] H pylori除菌治療後GERDと酸逆流関連症状発現のリスクの検討 (2020)
  • Author(s): 杉本光繁
  • Organizer: 2020年度日本消化器関連学会
• [Presentation] P-CABを第一選択としたGERD診療の功罪 (2020)
  • Author(s): 杉本光繁
  • Organizer: 第16回 日本消化管学会学術集会
  • Invited
• [Presentation] Genetic and bacterial factors for outcome of vonoprazan-containing Helicobacter pylori eradication therapy in Japanese (2019)
  • Author(s): Mitsushige Sugimoto, Masaki Murata, Taketo Otsuka, Atsushi Nishida, Osamu Inatomi, Shigeki Bamba, Akira Andoh
  • Organizer: DDW 2019
  • Int'l Joint Research
• [Presentation] 早期胃癌に対する内視鏡的粘膜下層剥離術後の人工潰瘍治癒におけるCYP2C19遺伝子多型の影響 (2019)
  • Author(s): 杉本 光繁 、伴 宏充
  • Organizer: 第40回 日本臨床薬理学会学術集会
• [Presentation] Eradication therapy for Helicobacter pylori improves nutrition status depended on severity of gastric mucosal atrophy and plasma ghrelin level in Japanese hemodialysis patients (2018)
  • Author(s): Sugimoto M, Otsuka T, Murata M, Ichikawa H, Sahara S, Andoh A
  • Organizer: American Collage of Gastroenterology
  • Int'l Joint Research