Gut microbiome meta-analysis reveals dysbiosis is independent of body mass index in predicting risk of obesity-associated CRC
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Abstract
OBJECTIVE: Obesity is a risk factor for colorectal cancer (CRC), accounting for more than 14% of CRC incidence. Microbial dysbiosis and chronic inflammation are common characteristics in both obesity and CRC. Human and murine studies, together, demonstrate the significant impact of the microbiome in governing energy metabolism and CRC development; yet, little is understood about the contribution of the microbiome to development of obesity-associated CRC as compared to individuals who are not obese. DESIGN: In this study, we conducted a meta-analysis using five publicly available stool and tissue-based 16S rRNA and whole genome sequencing (WGS) data sets of CRC microbiome studies. High-resolution analysis was employed for 16S rRNA data, which allowed us to achieve species-level information to compare with WGS. RESULTS: Characterisation of the confounders between studies, 16S rRNA variable region and sequencing method did not reveal any significant effect on alpha diversity in CRC prediction. Both 16S rRNA and WGS were equally variable in their ability to predict CRC. Results from diversity analysis confirmed lower diversity in obese individuals without CRC; however, no universal differences were found in diversity between obese and non-obese individuals with CRC. When examining taxonomic differences, the probability of being classified as CRC did not change significantly in obese individuals for all taxa tested. However, random forest classification was able to distinguish CRC and non-CRC stool when body mass index was added to the model. CONCLUSION: Overall, microbial dysbiosis was not a significant factor in explaining the higher risk of colon cancer among individuals with obesity.
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The meta-analysis could not establish that these taxa contributed to colorectal cancer development because the included studies were cross-sectional.
“it could not establish that these taxa contributed to development of CRC, due to the cross-sectional design of the included studies”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [109]
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- Authors
- Greathouse, K. L., White, J. R., Padgett, R. N., Perrotta, B. G., Jenkins, G. D., Chia, N., & Chen, J.
- Affiliations
- Baylor University (US)
- Resphera Biosciences (US)
- Mayo Clinic (US)
- Corresponding author
- Greathouse, K Leigh
- ORCID
- Venue
- BMJ Open Gastroenterology
- Publisher
- BMJ
- Published
- 2019-02
- Volume
- 6
- Issue
- 1
- Pages
- e000247
- ISSN
- 2054-4774 (ISSN-L)
- PMC
- PMC6398873
- OpenAlex
- W2953358317
- Cited by
- 35
- References
- 72
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 8 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open Gastroenterology (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Cancer Institute (R01CA179243)
- Baylor University (Summer Research Sabbatical)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- gut microbiota, colorectal cancer, obesity, dysbiosis, body mass index, alpha diversity, cancer risk prediction, stool microbiome, 16S rRNA, whole genome sequencing, random forest classification, energy metabolism, chronic inflammation
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