# The study on the identification of cross-boundary microbiome enterotypes between high-altitude and coastal populations and their predictive value

**Authors:** Jiawei Zhang, Jiaxin Deng, Bingfeng He, Han Wang, Dezheng Lin, Juan Li, Qinghua Zhong, Yongcheng Chen, Sen Liao, Junhao Wang, Yuying Wang, Mingli Su, Xuefeng Guo

PMC · DOI: 10.1186/s12866-025-04578-0 · 2026-01-29

## TL;DR

This study found that gut microbiome differences between high-altitude and coastal populations in China may be linked to lower colorectal adenoma risk in high-altitude regions.

## Contribution

The study identifies cross-boundary microbiome enterotypes and their predictive value for colorectal adenoma in geographically distinct populations.

## Key findings

- High-altitude populations show distinct bacterial, fungal, and archaeal enterotypes compared to coastal populations.
- Combining microbial features improves classification accuracy between geographic and disease groups (AUC = 0.84–0.85).
- Specific high-altitude enterotypes correlate with metabolic pathways and may be associated with lower CRA prevalence.

## Abstract

To investigate the differences in gut microbiome composition among multi-center populations from coastal and high-altitude regions of China and their association with colorectal adenoma (CRA).

Metagenomic sequencing was performed on stool samples collected from 295 participants. Diversity, principal component, and linear discriminant analyses were conducted to assess microbial composition and functional differences related to geography and disease status.

In high-altitude populations, bacterial enterotypes were predominantly Prevotella, fungal enterotypes Saccharomyces, and archaeal enterotypes Methanobrevibacter, differing from those in coastal populations. Combining bacterial, fungal, and archaeal features improved classification accuracy between high-altitude and coastal populations (AUC = 0.84) and between high-altitude and coastal adenoma patients (AUC = 0.85). Specific enterotypes were observed to correlate significantly with metabolic pathways in high-altitude populations.

Significant differences in gut microbiome enterotypes exist across geographic populations, with specific enterotypes in high-altitude populations potentially associated with a lower prevalence of CRA. These findings provide new insights into the gut microbiome–geography relationship and support microbiome-based diagnostic and therapeutic strategies.

The online version contains supplementary material available at 10.1186/s12866-025-04578-0.

What is already known on this topic: The gut microbiome plays a crucial role in the progression of adenomas to colorectal cancer, but how different geographic environments impact the gut microbiome remains unclear.

What this study adds: This study reveals significant differences in gut microbiome composition between high-altitude and coastal populations, highlighting potential protective effects in high-altitude areas.

How this study might affect research, practice or policy: Emphasizes the importance of geographic factors in developing personalized prevention and treatment strategies for CRA, underscoring the need for further longitudinal cohort studies to validate these findings and explore underlying mechanisms.

The online version contains supplementary material available at 10.1186/s12866-025-04578-0.

## Linked entities

- **Diseases:** colorectal adenoma (MONDO:0005484), colorectal cancer (MONDO:0005575)
- **Species:** Prevotella (taxon 838), Saccharomyces (taxon 4930), Methanobrevibacter (taxon 2172)

## Full-text entities

- **Genes:** PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** inflammation (MESH:D007249), colon cancer (MESH:D015179), Crohn's disease (MESH:D003424), cardiovascular or pulmonary diseases (MESH:D002318), diabetes (MESH:D003920), gastrointestinal diseases (MESH:D005767), adenoma-carcinoma (MESH:D000230), HAP (MESH:C535833), cancer (MESH:D009369), familial adenomatous polyposis (MESH:D011125), Digestive Diseases (MESH:D004066), severe acute malnutrition (MESH:D000067011), hypoxic (MESH:D002534), obesity (MESH:D009765), bleeding (MESH:D006470), inflammatory bowel disease (MESH:D015212), Adenoma (MESH:D000236), fungal (MESH:D009181), ulcerative colitis (MESH:D003093), colon tumor (MESH:D003110), hypoxia (MESH:D000860), infectious diseases (MESH:D003141)
- **Chemicals:** CP (-), histamine (MESH:D006632), salt (MESH:D012492), oxygen (MESH:D010100), sulfate (MESH:D013431), butyrate (MESH:D002087), methane (MESH:D008697), amino acid (MESH:D000596), heme (MESH:D006418), 2,3-butanediol (MESH:C026978), isoleucine (MESH:D007532), methylphosphonic acid (MESH:C032627), propionate (MESH:D011422), carbohydrate (MESH:D002241), leucine (MESH:D007930), carbon dioxide (MESH:D002245), lactulose (MESH:D007792), acetate (MESH:D000085), sulfite (MESH:D013447), hydrogen (MESH:D006859), SCFA (MESH:D005232), trimethylamine (MESH:C023336)
- **Species:** Faecalibacterium (genus) [taxon 216851], Streptococcus (genus) [taxon 1301], Methanosarcina (genus) [taxon 2207], Escherichia coli (E. coli, species) [taxon 562], Megamonas (genus) [taxon 158846], Thermococcus (genus) [taxon 2263], Hepacivirus P (species) [taxon 2202225], Synchytrium (genus) [taxon 286114], Kluyveromyces (genus) [taxon 4910], Botrytis (genus) [taxon 33196], Bacteroides (genus) [taxon 816], Sulfolobus (genus) [taxon 2284], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Methanosphaera (genus) [taxon 2316], Segatella copri (species) [taxon 165179], Malassezia (genus) [taxon 55193], Halorubrum (genus) [taxon 56688], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Bifidobacterium (genus) [taxon 1678], Homo sapiens (human, species) [taxon 9606], Candida [taxon 1535326], Phocaeicola (genus) [taxon 909656], Alternaria sect. Alternaria (section) [taxon 2499237], Yarrowia (genus) [taxon 4951], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Candidatus Nitrosocosmicus (genus) [taxon 1826864], Pseudocercospora (genus) [taxon 131324], Methanobrevibacter (genus) [taxon 2172], Saccharolobus (genus) [taxon 2100760], Mediterraneibacter (genus) [taxon 2316020], Klebsiella (genus) [taxon 570], Methanothrix (genus) [taxon 2222], Ruminococcus (genus) [taxon 1263], gut metagenome (species) [taxon 749906], Penicillium (genus) [taxon 5073], Parabacteroides (genus) [taxon 375288], Aspergillus (genus) [taxon 5052]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12973879/full.md

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Source: https://tomesphere.com/paper/PMC12973879