Sohyun Jeong, Yi‑Tyng Liao, Min‑Hsuan Tsai, Yao‑Kuang Wang, I‑Chen Wu, Chung‑Jung Liu, Ming‑Shun Wu, Tze‑Sian Chan, Ming‑Yao Chen, Ping‑Jen Hu, Wei‑Yu Kao, Hsiang‑Chin Liu, Ming‑Ju Tsai, Cheng‑Yuan Liu, Chun‑Chao Chang, Deng‑Chyang Wu, and Yi‑Hsiang Hsu
Background Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a noninvasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. Results A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was subgrouped into intestinal metaplasia (n=15) and non intestinal metaplasia (n=18); the gastric cancer group, early stage (stages 1 and 2, n=13) and late stage (stages 3 and 4, n=19) cancer. No signifcant diferences in alpha and beta diversities were detected among the patient groups. However, in a twogroup univariate comparison, higher Fusobacteria abundance was identifed in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q=0.041 in LEfSe). Age and sex adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful fea‑ tures; Bacteria_caccae was the most contributing species toward gastric cancer and latestage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifdobacterium_longum signifcantly contributed to chronic gastritis (beta:1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMIadjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUTPWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. Conclusion Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer [ABSTRACT FROM AUTHOR]