Novel Microbiome Signatures for Non-invasive Diagnosis of Adenoma Recurrence After Colonoscopic Polypectomy

Jessie Qiaoyi Liang; Yao Zeng; Grace Kwok; Chun Pan Cheung; Bing Yee Suen; Jessica Y. L. Ching; Ka Fai To; Jun Yu; Francis K. L. Chan; Siew Chien Ng


Aliment Pharmacol Ther. 2022;55(7):847-855. 

In This Article

Abstract and Introduction


Background: We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer.

Aim: To evaluate whether these markers are useful in detecting adenoma recurrence after polypectomy.

Methods: Subjects were enrolled in a polyp surveillance study from 2009 to 2019. Stool samples were collected before bowel preparation of index colonoscopy (baseline) and surveillance colonoscopy (follow-up). Fusobacterium nucleatum (Fn), Lachnoclostridium marker (m3), Clostridium hathewayi (Ch) and Bacteroides clarus were quantified in baseline and follow-up samples by quantitative polymerase chain reaction (qPCR) to correlate with adenoma recurrence. Recurrence was defined as new adenomas detected >6 months after polypectomy. Faecal immunochemical test (FIT) was performed for comparison.

Results: A total of 161 baseline and 104 follow-up samples were analysed. Among patients with adenoma recurrence, Fn and m3 increased (both P < 0.05) while Ch were unchanged in follow-up versus baseline samples. Among patients without recurrence, Fn and m3 were unchanged while Ch decreased (P < 0.05) in follow-up versus baseline samples. Logistic regression that included changes of m3, Fn and Ch at follow-up compared with baseline achieved an area under receiver operating characteristic curve (AUROC) of 0.95 (95%CI: 0.84–0.99) with 90.0% sensitivity and 87.0% specificity for detecting recurrent adenoma. Combination of m3, Fn and Ch at follow-up sample achieved AUROC of 0.74 (95%CI: 0.65–0.82) with 81.3% sensitivity and 55.4% specificity for detecting recurrent adenoma. FIT showed limited sensitivity (8.3%) in detecting recurrent adenomas.

Conclusion: Our combinations of faecal microbiome gene markers can be potentially useful non-invasive tools for detecting adenoma recurrence.


Colorectal cancer (CRC) is one of the most common cancers worldwide.[1] Most CRCs begin as adenomas. Adenomatous polyps can be detected in 20%-40% of patients undergoing screening colonoscopy, and their occurrence is associated with an increased risk of CRC. Although endoscopic removal of colorectal adenomas significantly reduces the risk of CRC, regular surveillance examination is needed as risk of recurrence after polypectomy ranges from 37% to 60%.[2] Recently, non-invasive biomarkers for CRC including stool and plasma tumour DNA have been approved by the U.S. Food and Drug Administration (FDA).[3,4] However, these DNA tests have low diagnostic accuracy for precancerous lesions, especially non-advanced adenomas, because genetic or epigenetic changes in cancerous cells are rarely present in small precancerous lesions.

Altered gut microbiota composition has been implicated in the initiation and progression of adenomas and CRC.[5–9] A direct causative role of gut microbiota for CRC development was demonstrated in germ-free animal models.[10] Specific bacterial pathogens, such as Fusobacterium nucleatum (Fn)[11–13] and Peptostreptococcus anaerobius,[14] have been proposed to promote colorectal tumorigenesis. We previously reported that certain bacterial gene markers in stool were useful as non-invasive tests for adenomas and CRC.[6,15–17] Using probe-based duplex quantitative polymerase chain reaction (qPCR) assays, we have identified a panel of bacterial gene markers of Fn, Lachnoclostridium sp. (m3), Clostridium/Hungatella hathewayi (Ch) and Bacteroides clarus (Bc) for the detection of adenoma and CRC.[15,16]Fn and Ch were found to be enriched in stool of patients with CRC.[15]m3 is enriched in both adenoma and CRC, whereas Bc is enriched in normal subjects.[15,16] Our previous findings indicated that these bacterial gene markers could also detect both advanced and non-advanced adenomas.[16] We hypothesised that these bacterial gene markers would be effective in detecting recurrent adenomas. In this study, we evaluated the diagnostic accuracy of Fn, m3, Ch and Bc for adenoma recurrence following colonoscopic polypectomy.