Gastric Microbiota in stomach precancerous conditions. A cooperative Muenchen-Padova Study

Background: Gastric microbiota (GMi) plays a significant role in metabolome shaping and it is also potentially involved in gastric oncogenesis.1,2 This international prospective cohort study investigates bacterial communities in stomachs with clinically, histologically, and serologically profiled precancerous conditions. Aims & Methods: The aim of the study was to evaluate whether a certain GMi composition could be related to a specific gastric pathological condition, in order to investigate its oncogenic potential. 112 biopsies from oxyntic and antral mucosa (healthy stomachs [HS] 36; Hp+ Gastritis (G): 21 atrophic [AG] and 22 non-atrophic [NAG]; Autoimmune G. [AIG] 33) were endoscopically obtained from 53 subjects (GE= 27; IT= 26). Serology was tested by Gastropanel. Histology assessment applied validated criteria, as the OLGA-staging system. GMi-communities were profiled by gastric biopsies 16S rRNA sequencing, calculating bacterial genus abundances across the tested conditions. - (Faith PD, Observed Features, Shannon Entropy) and - (PCoA) diversity were valued. The correlation of GMi with clinicopathological variables was tested by Spearman-test. P<0.05 was considered significant. Results: Multivariate testing revealed significant correlation only for diagnostic categories (p=.0001) in the study of the correlation between GMi-profile (all biopsy samples) and sex, age, country (GE vs IT), alcohol intake, smoking habit, PPI assumption, samples compartment (antrum vs corpus), and diagnostic category. HS samples featured the highest -diversity and, compared to each category, -diversity was sensibly higher, with elective abundance of Solobacterium, and Eubacterium Sulci genera (p<.05). In oxyntic and antral mucosa of NAG and AG samples, Helicobacter genus harmed the microbial community, leading to extremely low -diversity and is significantly -diverse from HS. Opposite to Hp+, AIG-GMi featured the microbial community similar to HS, with a prevalence of genus Granulicatella, Pauljensenia, Rothia, Parvimonas, and Veillonella (p<.05). This finding was further supported by the clustering of AIG and HS on the same side of the PCoA graph. By applying Spearman test, GMi profile showed significant correlation with patients’ clinicopathological profile: - Normal histology positively correlated with Solobacterium and Eubacterium and inversely with inflammatory score (polymorphs and lymphocytes) and with G17 and Pg2 (p<.05) - Hp+ NAG and AG positively correlated with inflammatory score (p<.05), with Pg1, Pg2 and Pg1/Pg2, and inversely correlated with APCA values (p<.05) - In oxyntic AIG samples, pseudopyloric atrophy positively correlated with Gemella, Granulicatella, and Veillonella, while Leptotrichia and Rothia with IM atrophy (p<.05) - Gemella, Granulicatella, Haemophilus parainfluenzae, Pauljensenia, Rothia and Veillonella positively correlated with APCA (p<.05), and inversely correlated with Pg1 (as marker of oxyntic atrophy). Conclusion: This study explored microbiota composition in gastric precancerous conditions. The present study provides evidence of clinico-biological correlation between GMi and precancerous atrophy and inflammation. The present results significantly link microbes others than Hp as promoters of the gastric inflammation and, ultimately, in gastric oncogenesis. The overlaps of GMi composition between HS and AIG may provide a biological rationale for the lower cancer risk of AIG compared to Hp+ atrophic patients.3 These results support the potential use of GMi profiling as add-on information in ranking the cancer risk in patients harboring gastric precancerous conditions.