Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls

doi:10.1007/s12029-023-00925-4

. 2024 Mar;55(1):207-218.

doi: 10.1007/s12029-023-00925-4. Epub 2023 Jun 13.

Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls

S B Rifkin^{1

2}, M A Sze³, K Tuck⁴, E Koeppe^{4

5}, E M Stoffel^{4

5}, P D Schloss³

Affiliations

¹ Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA. srifkin@med.umich.edu.
² Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA. srifkin@med.umich.edu.
³ Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴ Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵ Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.

PMID: 37310549
DOI: 10.1007/s12029-023-00925-4

Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls

S B Rifkin et al. J Gastrointest Cancer. 2024 Mar.

. 2024 Mar;55(1):207-218.

doi: 10.1007/s12029-023-00925-4. Epub 2023 Jun 13.

Authors

S B Rifkin^{1

2}, M A Sze³, K Tuck⁴, E Koeppe^{4

5}, E M Stoffel^{4

5}, P D Schloss³

Affiliations

¹ Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA. srifkin@med.umich.edu.
² Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA. srifkin@med.umich.edu.
³ Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴ Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵ Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.

PMID: 37310549
DOI: 10.1007/s12029-023-00925-4

Abstract

Background: While Lynch syndrome (LS) is a highly penetrant colorectal cancer (CRC) syndrome, there is considerable variation in penetrance; few studies have investigated the association between microbiome and CRC risk in LS. We analyzed the microbiome composition among individuals with LS with and without personal history of colorectal neoplasia (CRN) and non-LS controls.

Methods: We sequenced the V4 region of the 16S rRNA gene from the stool of 46 individuals with LS and 53 individuals without LS. We characterized within community and in between community microbiome variation, compared taxon abundance, and built machine learning models to investigate the differences in microbiome.

Results: There was no difference within or between community variations among LS groups, but there was a statistically significant difference in both within and between community variation comparing LS to non-LS. Streptococcus and Actinomyces were differentially enriched in LS-CRC compared to LS-without CRN. There were numerous differences in taxa abundance comparing LS to non-LS; notably, Veillonella was enriched and Faecalibacterium and Romboutsia were depleted in LS. Finally, machine learning models classifying LS from non-LS controls and LS-CRC from LS-without CRN performed moderately well.

Conclusions: Differences in microbiome composition between LS and non-LS may suggest a microbiome pattern unique to LS formed by underlying differences in epithelial biology and immunology. We found specific taxa differences among LS groups, which may be due to underlying anatomy. Larger prospective studies following for CRN diagnosis and microbiome composition changes are needed to determine if microbiome composition contributes to CRN development in patients with LS.

Keywords: Colorectal cancer (CRC); Colorectal neoplasia (CRN); DNA mismatch repair (MMR); Lynch syndrome (LS); Microbiome.

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References

1. Møller P, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464–72. https://doi.org/10.1136/gutjnl-2015-309675 . - DOI - PubMed
1. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575–82. https://doi.org/10.1038/nrmicro2819 . - DOI - PubMed
1. Wu S, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22. https://doi.org/10.1038/nm.2015 . - DOI - PubMed - PMC
1. Dejea CM, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359(6375):592–7. https://doi.org/10.1126/science.aah3648 . - DOI - PubMed - PMC
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[1] Møller P, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464–72. https://doi.org/10.1136/gutjnl-2015-309675 . - DOI - PubMed

[2] Møller P, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464–72. https://doi.org/10.1136/gutjnl-2015-309675 . - DOI - PubMed

[3] Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575–82. https://doi.org/10.1038/nrmicro2819 . - DOI - PubMed

[4] Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575–82. https://doi.org/10.1038/nrmicro2819 . - DOI - PubMed

[5] Wu S, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22. https://doi.org/10.1038/nm.2015 . - DOI - PubMed - PMC

[6] Wu S, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22. https://doi.org/10.1038/nm.2015 . - DOI - PubMed - PMC

[7] Dejea CM, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359(6375):592–7. https://doi.org/10.1126/science.aah3648 . - DOI - PubMed - PMC

[8] Dejea CM, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359(6375):592–7. https://doi.org/10.1126/science.aah3648 . - DOI - PubMed - PMC

[9] Arthur JC, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338(6103):120–3. https://doi.org/10.1126/science.1224820 . - DOI - PubMed - PMC

[10] Arthur JC, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338(6103):120–3. https://doi.org/10.1126/science.1224820 . - DOI - PubMed - PMC

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Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls

Affiliations

Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls

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