Background: Although infection with Helicobacter pylori and subsequent atrophic gastritis modulate the gastric conditions, their relationship with the gut microbiota in ­Japanese population has not been clearly characterized. Methods: A cohort of 1,123 subjects who participated in a health survey was studied. Infection of H. pylori was defined by both serum antibody and stool antigen test. The presence and severity of atrophic gastritis were defined by serum levels of pepsinogens. The relative abundance of each bacterial species in fecal samples was calculated by using 16S ribosomal RNA amplification, and the composition ratios of bacterial taxa were evaluated using propensity score matching. Results: The abundance of 3 orders, 4 families, and 4 genera was significantly higher in H. pylori-infected subjects than in noninfected subjects (false discovery rate [FDR] <0.05). In H. pylori-infected subjects with severe atrophic gastritis, the abundance of the class Bacilli, order Lactobacillales, family Streptococcaceae, and genus Streptococcus was significantly higher than that in H. pylori-infected subjects without atrophic gastritis (FDR < 0.05). Conclusions: A significant increase in the relative abundance of several taxa was observed in gut microbiota of Japanese subjects with H. pylori infection. Among the subjects with severe atrophic gastritis, the increase in the genus Streptococcus is a remarkable characteristic.

1.
Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, et al. Evolution of mammals and their gut microbes. Science. 2008 Jun; 320(5883): 1647–51.
2.
Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011 Jun; 474(7351): 327–36.
3.
Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC, et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology. 2015 Oct; 149(4): 883–5.e9.
4.
Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016 May; 65(5): 740–8.
5.
Jackson MA, Goodrich JK, Maxan ME, Freedberg DE, Abrams JA, Poole AC, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016 May; 65(5): 749–56.
6.
Otsuka T, Sugimoto M, Inoue R, Ohno M, Ban H, Nishida A, et al. Influence of potassium-competitive acid blocker on the gut microbiome of Helicobacter pylori-negative healthy individuals. Gut. 2017 Sep; 66(9): 1723–5.
7.
Takagi T, Naito Y, Inoue R, Kashiwagi S, Uchiyama K, Mizushima K, et al. The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study. J Clin Biochem Nutr. 2018 Jan; 62(1): 100–5.
8.
Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006 Jul; 19(3): 449–90.
9.
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001 Sep; 345(11): 784–9.
10.
Iino C, Shimoyama T, Chinda D, Arai T, Chiba D, Nakaji S, et al. Infection of Helicobacter pylori and atrophic gastritis influence Lactobacillus in gut microbiota in a Japanese population. Front Immunol. 2018 Apr; 9: 712.
11.
Bühling A, Radun D, Müller WA, Malfertheiner P. Influence of anti-Helicobacter triple-therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora. Aliment Pharmacol Ther. 2001 Sep; 15(9): 1445–52.
12.
Hsu PI, Pan CY, Kao JY, Tsay FW, Peng NJ, Kao SS, et al.; Taiwan Acid-related Disease (TARD) Study Group. Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria. Helicobacter. 2018 Aug; 23(4):e12498.
13.
Yanagi H, Tsuda A, Matsushima M, Takahashi S, Ozawa G, Koga Y, 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 Gastroenterol. 2017 Nov; 4(1):e000182.
14.
Nishijima S, Suda W, Oshima K, Kim SW, Hirose Y, Morita H, et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res. 2016 Apr; 23(2): 125–33.
15.
Kawai T, Kawakami K, Kudo T, Ogiahara S, Handa Y, Moriyasu F. A new serum antibody test kit (E plate) for evaluation of Helicobacter pylori eradication. Intern Med. 2002 Oct; 41(10): 780–3.
16.
Sato M, Shimoyama T, Takahashi R, Kajiyama H, Sano Y, Sakaedani N, et al. Characterization and usefulness of stool antigen tests using a monoclonal antibody to Helicobacter pylori catalase. J Gastroenterol Hepatol. 2012 Apr; 27(suppl 3): 23–8.
17.
Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 2006; 9(4): 245–53.
18.
Urita Y, Hike K, Torii N, Kikuchi Y, Kanda E, Sasajima M, et al. Serum pepsinogens as a predicator of the topography of intestinal metaplasia in patients with atrophic gastritis. Dig Dis Sci. 2004 May; 49(5): 795–801.
19.
Kishikawa H, Nishida J, Ichikawa H, Kaida S, Takarabe S, Matsukubo T, et al. Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status. Helicobacter. 2011 Dec; 16(6): 427–33.
20.
Takahashi S, Tomita J, Nishioka K, Hisada T, Nishijima M. Development of a prokaryotic universal primer for simultaneous analysis of Bacteria and Archaea using next-generation sequencing. PLoS One. 2014 Aug; 9(8):e105592.
21.
Hisada T, Endoh K, Kuriki K. Inter- and intra-individual variations in seasonal and daily stabilities of the human gut microbiota in Japanese. Arch Microbiol. 2015 Sep; 197(7): 919–34.
22.
Giannella RA, Broitman SA, Zamcheck N. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro. Gut. 1972 Apr; 13(4): 251–6.
23.
Gao JJ, Zhang Y, Gerhard M, Mejias-Luque R, Zhang L, Vieth M, et al. Association between gut microbiota and Helicobacter pylori-related gastric lesions in a high-risk population of gastric cancer. Front Cell Infect Microbiol. 2018 Jun; 8: 202.
24.
Takagi T, Naito Y, Inoue R, Kashiwagi S, Uchiyama K, Mizushima K, et al. Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects. J Gastroenterol. 2019 Jan; 54(1): 53–63.
25.
Schulz C, Schütte K, Koch N, Vilchez-Vargas R, Wos-Oxley ML, Oxley AP, et al. The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection. Gut. 2018 Feb; 67(2): 216–25.
26.
Rodríguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015 Feb; 26: 26050.
27.
Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 2016 May; 16(1): 90.
28.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec; 444(7122): 1022–3.
29.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec; 444(7122): 1027–31.
30.
Menni C, Jackson MA, Pallister T, Steves CJ, Spector TD, Valdes AM. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. Int J Obes. 2017 Jul; 41(7): 1099–105.
31.
Borgo F, Garbossa S, Riva A, Severgnini M, Luigiano C, Benetti A, et al. Body mass index and sex affect diverse microbial niches within the Gut. Front Microbiol. 2018 Feb; 9: 213.
32.
Iijima K, Koike T, Abe Y, Shimosegawa T. Cutoff serum pepsinogen values for predicting gastric acid secretion status. Tohoku J Exp Med. 2014 Apr; 232(4): 293–300.
You do not currently have access to this content.