Structure of the Mucosal and Stool Microbiome in Lynch Syndrome

Yan, Yan; Drew, David A.; Markowitz, Arnold J.; Lloyd-Price, Jason; Abu-Ali, Galeb; Nguyen, Long H.; Tran, Christina; Chung, Daniel C.; Gilpin, Katherine K.; Meixell, Dana; Parziale, M; Schuck, Madeline M.; Patel, Zalak; Richter, James M.; Kelsey, Peter B.; Garrett, Wendy S.; Chan, Andrew T.; Stadler, Zsofia K.; Huttenhower, Curtis

doi:10.1016/j.chom.2020.03.005

Cited by 48 publications

(62 citation statements)

References 85 publications

(76 reference statements)

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“…A colectomy can change the overall microbiome structure. Nonetheless, baseline differences in mucosal and fecal community function were concordant with previously observed changes in later-stage CRC and weakly predictive of interval adenoma development [ 27 ]. Moreover, LS patients with CRC had fecal microbial communities similar to those from LS patients with gynecological tumors [ 28 ].…”

Section: Introductionsupporting

confidence: 85%

Oral and Fecal Microbiota in Lynch Syndrome

Ferrarese

Zuppardo

Puzzono

et al. 2020

JCM

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Background: The role of microbiota in Lynch syndrome (LS) is still under debate. We compared oral and fecal microbiota of LS saliva and stool samples with normal healthy controls (NHC). Methods: Total DNA was purified from feces and saliva to amplify the V3–V4 region of the 16s rRNA gene. Sequences with a high-quality score and length >250 bp were used for taxonomic analysis with QIIME software. Results: Compared to NHC, LS fecal samples demonstrated a statistically significant increase of Bacteroidetes and Proteobacteria and a significant decrease of Firmicutes at the phylum level and of Ruminococcaceae at the family level. Moreover, LS oral samples exhibited a statistically significant increase of Veillonellaceae and Leptotrichiaceae and a statistically significant decrease of Pasteurellaceae. A beta-diversity index allowed differentiation of the two groups. Conclusions: A peculiar microbial signature is associated with LS, similar to that of sporadic colorectal cancer and Crohn’s disease. These data suggest a possible role of proinflammatory bacteria in tumor development in a condition of genetic predisposition, such as LS.

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Section: Introductionsupporting

confidence: 85%

Oral and Fecal Microbiota in Lynch Syndrome

Ferrarese

Zuppardo

Puzzono

et al. 2020

JCM

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“…In a recent study, the colonic biopsy and fecal microbiotas of patients with LS and their relationship with the development of colonic pre-neoplastic lesions was investigated [ 119 ]. Microbiota associated with patients’ adenomas were assessed at baseline and after 1 to 2 years of follow-up, finding that commensal bacteria with pathobiont-like behavior, broadly influencing whole-gut ecology and metabolism, were the ones associated with adenomas and/or disease progression.…”

Section: Microbial Biomarkers In Sporadic and Hereditary Crcmentioning

confidence: 99%

“…Microbiota associated with patients’ adenomas were assessed at baseline and after 1 to 2 years of follow-up, finding that commensal bacteria with pathobiont-like behavior, broadly influencing whole-gut ecology and metabolism, were the ones associated with adenomas and/or disease progression. However, the authors detected some abundant species (prevalence >90%) in stool samples of LS patients, such as Eubacterium rectale , Bacteroides uniformis , and Faecalibacterium prausnitzii [ 119 ].…”

Section: Microbial Biomarkers In Sporadic and Hereditary Crcmentioning

confidence: 99%

“…Clinical factors that are specific to LS patients, such as medications used, surgery type and gene mutations, are significantly associated with individual taxonomic members of the mucosal and/or stool communities [ 119 ] ( Table 3 ).…”

Section: Microbial Biomarkers In Sporadic and Hereditary Crcmentioning

confidence: 99%

“…Yan et al reported individual microbes associated with Lynch-relevant clinical factors, with members of the Clostridiaceae family being significantly depleted in the stool microbiota of individuals with adenomas, while Lachnospiraceae and Ruminococcaceae significantly enriched [ 119 ]. Biopsy samples were enriched in Methanobrevibacter , while Desulfovibrio was enriched in both stool and biopsy samples [ 119 ]. Among the LS related clinical factors the authors investigated, the potential effects of specific mismatch repair genes ( MLH1, MSH2, MSH6, PMS2 ) on the microbiota was described.…”

Section: Microbial Biomarkers In Sporadic and Hereditary Crcmentioning

confidence: 99%

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Gut Microbial Signatures in Sporadic and Hereditary Colorectal Cancer

Mori

Pasca

2021

IJMS

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Colorectal cancer (CRC) is the fourth most common cause of cancer-related death and the third most common cancer in the world. Depending on the origin of the mutation, colorectal carcinomas are classified as sporadic or hereditary. Cancers derived from mutations appearing during life, affecting individual cells and their descendants, are called sporadic and account for almost 95% of the CRCs. Less than 5% of CRC cases result from constitutional mutations conferring a very high risk of developing cancer. Screening for hereditary-related cancers is offered to individuals at risk for hereditary CRC, who have either not undergone genetic evaluation or have uncertain genetic test results. In this review, we briefly summarize the main findings on the correlation between sporadic CRC and the gut microbiota, and we specifically focus on the few evidences about the role that gut microorganisms have on the development of CRC hereditary syndromes. The characterization of a gut microbiota associated with an increased risk of developing CRC could have a profound impact for prevention purposes. We also discuss the potential role of the gut microbiota as therapeutic treatment.

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Alterations in the oral and gut microbiome of colorectal cancer patients and association with host clinical factors

Wang

Zhang

Qian

et al. 2021

Intl Journal of Cancer

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Previous studies have suggested that gut microbiota plays a critical role in colorectal cancer (CRC). Although preliminary comparisons of the oral and gut microbiota between CRC and healthy control (HC) patients have been made, the association between microbiome abundance and host clinical factors has not been fully illustrated, especially oral health conditions. Matching samples of unstimulated saliva, cancer tissues or biopsies and stools were collected from 30 CRC and 30 HC patients from Shanghai Jiao Tong University affiliated Renji Hospital for 16S rRNA sequencing analysis. The diversity in salivary and mucosal microbiome, but not stool microbiome of CRC group, was significantly different from that of HC, as demonstrated by the Principal Component Analysis. Logistic regression analysis revealed that older age and higher oral hygiene index (OHI) were independent risk factors for CRC, with odds ratios and 95% confidence intervals of 1.159 (1.045‐1.284) and 4.398 (1.328‐14.567), respectively. Salivary Firmicutes to Bacteroides ratio in CRC was significantly higher than that in the HC group (P < .001), while the mucosal ratio was slightly decreased in CRC (P < .05). Salivary Rothia and Streptococcus levels were positively correlated with OHI, while Alloprevotella, Fusobacterium, Peptostreptoccus and Prevotella genera levels were negatively associated with OHI. NetShift analysis revealed that salivary Peptococcus, Centipeda and mucosal Subdoligranulum genus might act as key drivers during the process of carcinogenesis. In conclusion, the current study provides insights into the potential influence of host clinical factors on oral and gut microbiome composition and can be a guide for future studies.

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Structure of the Mucosal and Stool Microbiome in Lynch Syndrome

Abstract: Highlights d Gut microbial changes in Lynch adenoma resemble later stage CRC with smaller effect d Colectomy with CRC history represented the largest effect on the Lynch microbiome d Feces metatranscriptome weakly predicted future preneoplastic adenoma development

Cited by 48 publications

References 85 publications

Oral and Fecal Microbiota in Lynch Syndrome

Oral and Fecal Microbiota in Lynch Syndrome

Gut Microbial Signatures in Sporadic and Hereditary Colorectal Cancer

Alterations in the oral and gut microbiome of colorectal cancer patients and association with host clinical factors

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