Gastric Microbiota Could Be a Key Biomarker for Gastric Cancer

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Gastric Microbiota Could Be a Key Biomarker for Gastric Cancer

Gastric cancer (GC) is one of the most common and deadly cancers worldwide, affecting millions of people each year. While factors like Helicobacter pylori infection, diet, and genetics are well-known risk factors, emerging research suggests that an abnormal gastric microbiota—the community of bacteria living in the stomach—plays a critical role in GC development. A 2020 study from researchers at Nanjing Medical University and Suzhou PrecisionGene Biotechnology Co. Ltd. explores how these bacteria could serve as diagnostic biomarkers for GC, offering a new tool to detect the disease earlier.

The Study: Linking Gastric Bacteria to Cancer

The research included 60 patients from the First Affiliated Hospital of Nanjing Medical University (2017–2018): 17 with chronic gastritis (CG), 13 with intestinal metaplasia (IM, a pre-cancerous condition), and 30 with GC. All participants provided written informed consent, and the study was approved by the hospital’s ethics committee.

To analyze the gastric microbiota, the team sequenced the V3-V4 region of 16S rRNA—a standard method to identify bacterial species—in tissue samples from the stomach. They used tools like QIIME (Quantitative Insights Into Microbial Ecology) to process data and LEfSe (Linear Discriminant Analysis Effect Size) to find bacteria with significant abundance differences between groups. For diagnostic modeling, they used leave-one-out cross-validation (LOOCV), a rigorous technique where each sample is tested individually using a model trained on almost all other samples.

Key Results: A Unique “Microbial Signature” for GC

The team found clear differences in the gastric microbiota between GC and non-GC (CG/IM) patients:

  1. Higher Bacterial Diversity in GC: GC patients had significantly more diverse stomach bacteria (measured by the Chao Index and Shannon Index) than those with CG or IM. This means their stomachs had more types of bacteria, and those bacteria were more evenly distributed—an indicator of “dysbiosis” (imbalance) linked to disease.

  2. Distinct Microbial Composition: A principal coordinates analysis (PCoA) plot showed that GC patients’ microbiota was significantly different from non-GC patients. This “signature” could help distinguish GC from less severe conditions.

  3. Diagnostic Biomarkers: LEfSe analysis identified 21 bacterial taxa (operational taxonomic units, OTUs) more common in GC and 6 more common in non-GC. The team built a LOOCV model using 19 of these OTUs (including Barnesiellaceae, Bacteroides uniformis, and Prevotella copri). The model performed well: it had an 89.3% area under the curve (AUC), meaning it could distinguish GC from non-GC with high accuracy. Sensitivity (ability to detect GC) was 83.3%, and specificity (ability to rule out GC) was 90%.

How These Bacteria May Drive GC

To understand why these bacteria matter, the team used KEGG (a database of biological pathways) to predict microbial functions. They found:

  • Increased Metabolic Activity: 29 pathways were more active in GC samples, mostly related to metabolism—like primary/secondary bile acid biosynthesis, sphingolipid metabolism, and drug metabolism. Bile acids are particularly notable: previous studies link bile acid receptors (e.g., TGR5) to gastric cancer cell growth and worse survival.
  • Reduced Protective Pathways: Pathways for folate biosynthesis (vitamin B9, critical for cell health) and gastric acid secretion were less active in GC. Lower folate and stomach acid may create an environment where cancer cells thrive.

Why This Matters for Diagnosis

Previous studies used tools like LEfSe (to find GC-associated species) or SparCC (to analyze bacterial correlations) to build diagnostic models. The LOOCV approach here has key advantages:

  • It tests every sample individually, avoiding grouping bias.
  • It uses almost all data for training, reducing error.
  • It’s reproducible (no random factors).

While LOOCV is more computationally intensive, it’s highly reliable—making it a strong candidate for future clinical use.

Limitations and Next Steps

The study’s small sample size (60 patients) means the biomarker set needs validation in larger, more diverse groups. However, the results are promising: gastric microbiota could one day complement existing tests (like endoscopy or blood markers) to detect GC earlier, when treatment is most effective. The team also plans to study which bacteria drive these metabolic changes—for example, how increased bile acid production from certain species promotes cancer.

Final Takeaway

Gastric cancer is often diagnosed late, but our stomach bacteria may hold the key to early detection. This study adds to growing evidence that the gastric microbiota is a critical player in GC development—and that specific bacterial species could serve as life-saving biomarkers. As research expands, we may soon see microbiome-based tests that help catch GC before it’s too late.

Yi-Ni Dang, Yu Dong, Yan-Zhao Mu, Jin Yan, Min Lu, Yong-Liang Zhu, and Guo-Xin Zhang conducted this research. The team included researchers from the First Affiliated Hospital of Nanjing Medical University, Nanjing First Hospital, Suzhou PrecisionGene Biotechnology Co. Ltd., and PrecisionGene, Inc. The study was published in the Chinese Medical Journal in 2020.

doi.org/10.1097/CM9.0000000000001081

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