Background: Functional dyspepsia (FD) is associated with poor health-related quality of life. Recent evidence suggests that the main pathogenesis suspect is the gut mucosa-associated microbiota (MAM). However, little is known about the MAM in FD subjects. The aim of this study was to clarify the relationship between upper gastrointestinal symptoms in FD and the characteristics of the gastrointestinal MAM. Summary: Five mucosa samples from the upper gut (intraoral, mid-esophagus, gastric body, gastric antrum, and descending portion of the duodenum) were collected with a brush under endoscopic examination from FD and healthy control subjects. MAM profiles of each sample were analyzed by 16S-rRNA ­V3-V4 gene sequences. Questionnaire was used to assess gastrointestinal symptoms in FD. Between FD and healthy control subjects, although the comparison of MAM α-diversity showed no significant differences, the structure of MAM (β-diversity) was clearly different. Only the phylum Firmicutes was increased in FD compared to healthy control subjects in all sites of the upper gut. At the genus level, Streptococcus was significantly increased in all sites in the upper gut in FD. The relative abundance of Streptococcus was positively correlated with upper gastrointestinal symptoms in each upper gut group. Furthermore, the relative abundance of OTU 90 was positively correlated with upper gastrointestinal symptoms in all sites in the upper gut in FD. Key Messages:Streptococcus is a bacterium strongly correlated with upper gastrointestinal symptoms in FD.

1.
Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal Disorders. Gastroenterology. 2016 May;150(6):1380–92.
2.
Tack J, Pokrotnieks J, Urbonas G, Banciu C, Yakusevich V, Bunganic I, et al. Long-term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)-results from the European phase 3 open-label safety trial. Neurogastroenterol Motil. 2018 Jun;30(6):e13284.
3.
Jung HK, Talley NJ. Role of the duodenum in the pathogenesis of functional dyspepsia: A paradigm shift. J Neurogastroenterol Motil. 2018 Jul;24(3):345–54.
4.
Stanghellini V, Ghidini C, Maccarini MR, Paparo GF, Corinaldesi R, Barbara L. Fasting and postprandial gastrointestinal motility in ulcer and non-ulcer dyspepsia. Gut. 1992 Feb;33(2):184–90.
5.
Thumshirn M, Camilleri M, Saslow SB, Williams DE, Burton DD, Hanson RB. Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function. Gut. 1999 Jan;44(1):55–64.
6.
Stanghellini V, Tosetti C, Paternico A, Barbara G, Morselli-Labate AM, Monetti N, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996 Apr;110(4):1036–42.
7.
Talley NJ, Walker MM, Aro P, Ronkainen J, Storskrubb T, Hindley LA, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol Hepatol. 2007 Oct;5(10):1175–83.
8.
Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita ÅV, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014 Feb;63(2):262–71.
9.
Zhong L, Shanahan ER, Raj A, Koloski NA, Fletcher L, Morrison M, et al. Dyspepsia and the microbiome: time to focus on the small intestine. Gut. 2017 Jun;66(6):1168–9.
10.
Andoh A. Physiological Role of Gut Microbiota for Maintaining Human Health. Digestion. 2016;93(3):176–81.
11.
Quigley EM. Gut microbiome as a clinical tool in gastrointestinal disease management: are we there yet? Nat Rev Gastroenterol Hepatol. 2017 May;14(5):315–20.
12.
Ringel Y, Maharshak N, Ringel-Kulka T, Wolber EA, Sartor RB, Carroll IM. High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes. 2015;6(3):173–81.
13.
Nishino K, Nishida A, Inoue R, Kawada Y, Ohno M, Sakai S, et al. Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease. J Gastroenterol. 2018 Jan;53(1):95–106.
14.
Kashiwagi S, Naito Y, Inoue R, Takagi T, Nakano T, Inada Y, et al. Mucosa-associated microbiota in the gastrointestinal tract of healthy Japanese subjects. Digestion. 2019, Epub ahead of print.
15.
Inoue R, Sakaue Y, Sawai C, Sawai T, Ozeki M, Romero-Pérez GA, et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders. Biosci Biotechnol Biochem. 2016 Dec;80(12):2450–8.
16.
Furuta K, Ishihara S, Sato S, Miyake T, Ishimura N, Koshino K, et al. [Development and verification of the Izumo Scale, new questionnaire for quality of life assessment of patients with gastrointestinal symptoms]. Nihon Shokakibyo Gakkai Zasshi. 2009 Oct;106(10):1478–87.
17.
Kinoshita Y, Chiba T.; FUTURE Study Group. Characteristics of Japanese patients with chronic gastritis and comparison with functional dyspepsia defined by ROME III criteria: based on the large-scale survey, FUTURE study. Intern Med. 2011;50(20):2269–76.
18.
Shimura S, Ishimura N, Mikami H, Okimoto E, Uno G, Tamagawa Y, et al. Small intestinal bacterial overgrowth in patients with refractory functional gastrointestinal disorders. J Neurogastroenterol Motil. 2016 Jan;22(1):60–8.
19.
Parks DH, Tyson GW, Hugenholtz P, Beiko RG. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics. 2014 Nov;30(21):3123–4.
20.
Nakae H, Tsuda A, Matsuoka T, Mine T, Koga Y. Gastric microbiota in the functional dyspepsia patients treated with probiotic yogurt. BMJ Open Gastroenterol. 2016 Sep;3(1):e000109.
21.
Marcial G, Villena J, Faller G, Hensel A, de Valdéz GF. Exopolysaccharide-producing Streptococcus thermophilus CRL1190 reduces the inflammatory response caused by Helicobacter pylori. Benef Microbes. 2017 May;8(3):451–61.
22.
Kawamura Y, Hou XG, Todome Y, Sultana F, Hirose K, Shu SE, et al. Streptococcus peroris sp. nov. and Streptococcus infantis sp. nov., new members of the Streptococcus mitis group, isolated from human clinical specimens. Int J Syst Bacteriol. 1998 Jul;48(Pt 3):921–7.
23.
Sultana F, Kawamura Y, Hou XG, Shu SE, Ezaki T. Determination of 23S rRNA sequences from members of the genus Streptococcus and characterization of genetically distinct organisms previously identified as members of the Streptococcus anginosus group. FEMS Microbiol Lett. 1998 Jan;158(2):223–30.
24.
Sabharwal A, Liao YC, Lin HH, Haase EM, Scannapieco FA. Draft genome sequences of 18 oral streptococcus strains that encode amylase-binding proteins. Genome Announc. 2015 May;3(3):e00510-15.
25.
Ciric L, Brouwer MS, Mullany P, Roberts AP. Minocycline resistance in an oral Streptococcus infantis isolate is encoded by tet(S) on a novel small, low copy number plasmid. FEMS Microbiol Lett. 2014 Apr;353(2):106–15.
26.
İriboz E, Arıcan Öztürk B, Kolukırık M, Karacan I, Sazak Öveçoğlu H. Detection of the unknown components of the oral microflora of teeth with periapical radiolucencies in a Turkish population using next-generation sequencing techniques. Int Endod J. 2018 Dec;51(12):1349–57.
27.
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.
28.
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.
29.
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.
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