Tongue Coating Bacteria as a Potential Stable Biomarker for Gastric Cancer Independent of Lifestyle

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ORIGINAL ARTICLE

Tongue Coating Bacteria as a Potential Stable Biomarker for Gastric Cancer Independent of Lifestyle Shuo Xu1 · Chunjie Xiang1 · Juan Wu1 · Yuhao Teng2 · Zhenfeng Wu3 · Ruiping Wang2 · Bin Lu4 · Zhen Zhan1 · Huangan Wu5,7 · Junfeng Zhang1,6  Received: 5 March 2020 / Accepted: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Background  Gastric cancer (GC) is one of the most common cancers, and the noninvasive diagnostic methods for monitoring GC are still lacking. Growing evidence shows that human microbiota has potential value for identifying digestive diseases. Aims  The present study aimed to explore the association of the tongue coating microbiota with the serum metabolic features and inflammatory cytokines in GC patients and seek a potential, noninvasive biomarker for diagnosing GC. Methods  The tongue coating microbiota was profiled by 16S rRNA and 18S rRNA genes sequencing technology in the original population with 181 GC patients and 112 healthy controls (HCs). Propensity score matching method was used to eliminate potential confounders including age, gender, and six lifestyle factors and a matching population with 66 GC patients and 66 HCs generated. Serum metabolomics profiling was performed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in the matching population. Random forest model was constructed for the diagnosis of GC. Results  Linear discriminant analysis effect size (LEfSe) revealed that the differential bacterial taxa between GC patients and HCs in the matching population were similar to that in the original population, while the differential fungal taxa between GC patients and HCs dramatically changed before and after PSM. By random forest analysis, the combination of six bacterial genera (Peptostreptococcus, Peptococcus, Porphyromonas, Megamonas, Rothia, and Fusobacterium) was the optimal predictive model to distinguish GC patients from HCs effectively, with an area under the curve (AUC) value of 0.85. The model was verified with a high predictive potential (AUC = 0.76 to 0.96). In the matching population, eighteen specific HCsenriched bacterial genera (Porphyromonas, Parvimonas, etc.) had negative correlations with lysophospholipids metabolites, and three of them had also negative correlations with serum IL-17α. Conclusions  The alteration of tongue coating microbiota had a possible linkage with the inflammations and metabolome, and the tongue coating bacteria could be a potential noninvasive biomarker for diagnosing GC, which might be independent of lifestyle. Keywords  Gastric cancer · Tongue coating · Bacteria · Fungi · Biomarker · Lifestyle Abbreviations GC Gastric cancer HCs Healthy controls AUC​ Area under the curve Shuo Xu and Chunjie Xiang have contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1062​0-020-06637​-0) contains supplementary material, which is available to authorize