Microbiome insights into pediatric familial adenomatous polyposis
Thomas M Attard1, Seth Septer2, Caitlin E Lawson3
1Department of Gastroenterology, Children's Mercy Hospital, 1MO2.37, 2401 Gilham Road, Kansas City, MO, 64108, USA.
Insights
Familial adenomatous polyposis (FAP) is linked to significant changes in gut microbiome diversity and composition. Specific bacterial markers in stool and tissue may help identify individuals at higher risk for FAP-related polyps.
Area of Science:
- Microbiome research
- Gastrointestinal oncology
- Pediatric genetics
Background:
- Familial adenomatous polyposis (FAP) is characterized by numerous precancerous polyps.
- The tumor microenvironment in FAP is influenced by a dysbiotic microbiome.
- Understanding these microbial shifts is crucial for early detection and management.
Purpose of the Study:
- To comprehensively analyze the stool and tissue microbiome in pediatric FAP subjects.
- To compare the microbiome of FAP patients with unaffected relatives.
- To identify microbial signatures associated with polyp development using machine learning.
Main Methods:
- 16S V4 region amplicon sequencing of stool and tissue samples.
- Machine learning algorithms for microbial data analysis.
- Comparison between FAP patients and healthy cohabiting controls.
Main Results:
- Proteobacteria dominated polyp/non-polyp mucosa, while Firmicutes and Bacteroidetes were predominant in stool/tissue.
- Reduced diversity and altered abundance of specific bacteria (e.g., Faecalibacterium, Bacteroides) were observed in FAP polyps and stool.
- Machine learning identified distinct bacterial markers in stool (e.g., Micrococcus luteus) and tissue (e.g., Blastocatellaceae) differentiating FAP patients.
Conclusions:
- Microbiome alterations, including shifts in specific bacterial taxa and diversity, are associated with FAP.
- Certain bacterial concentrations in stool or polyps could serve as biomarkers for FAP risk stratification.
- These findings support the potential of microbiome analysis as an adjunct to current FAP screening methods.
Background:
Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms.
Results:
Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides in the FAP stool. The alpha- and beta-diversity indices differed significantly within the polyp/non-polyp groups, with a concurrent shift towards lower diversity in polyps. In a limited 3-year longitudinal study, the relative abundance of Proteobacteria and Fusobacteria was higher in polyps compared to non-polyp and stool specimens over time. Through machine learning, we discovered that Archaeon_enrichment_culture_clone_A13, Micrococcus_luteus, and Eubacterium_hallii in stool and PL-11B10, S1-80, and Blastocatellaceae in tissues were significantly different between patients with and without polyps.
Conclusions:
Detection of certain bacterial concentrations within stool or biopsied polyps could serve as adjuncts to current screening modalities to help identify higher-risk patients.
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