A novel faecalLachnoclostridiummarker for the non-invasive diagnosis of colorectal adenoma and cancer

Abstract

ObjectiveThere is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.DesignThis study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.ResultsMetagenomic analysis identified ‘m3’ from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal m3 may perform better than Fn in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) m3=0.675 vs Fn=0.620, p=0.09), while Fn performed better in diagnosing CRC (AUROCs Fn=0.862 vs m3=0.741, p<0.0001). At 78.5% specificity, m3 and Fn showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), m3 performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by m3 (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of m3 for advanced adenoma to 56.8%. The combination of m3 with Fn, Ch, Bacteroides clarus and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%).ConclusionThis study identifies a novel bacterial marker m3 for the non-invasive diagnosis of colorectal adenoma.

Dynamics of Dark Fermentation Microbial Communities in the Light of Lactate and Butyrate Production

“…Paraclostridium strain CR4 was isolated from sugar cane bagasse involved in hydrogen and butyric acid production [52]. Other genera were found in and were isolated from human intestine microbiome [53][54][55][56].…”

“…Interestingly, studies on the microbiomes from the patients with autism spectrum disorder revealed an increased number of Terrisporobacter, Lachnoclostridium [55]. Lachnoclostridium was identi ed as a novel bacterial marker for the non-invasive diagnosis of colorectal adenoma [56]. It was also found that most of the gut butyrate-producing bacteria were signi cantly decreased in patients with non-small-cell lung cancer compared to healthy adults [57].…”

Alteration of the abundance of <em>Parvimonas&nbsp;micra</em> in the gut along the adenoma‑carcinoma sequence

“…For the qPCR method, the abundance (A) of P. micra in a sample was calculated as the ΔCq relative to the total bacterial DNA in the sample, and the relative abundance was calculated as ln (A × 10 9 +1). For 16S rRNA sequencing data, the A of an OTU in a sample was calculated as the ratio of the sequence count of the OTU relative to the total number of sequences in the sample, and the relative abundance of the OTU was determined as ln (A × 10 6 +1) ( 38 ). Differentially abundant OTUs were selected with the Wilcoxon rank-sum test for the comparison of healthy subjects with the CRC or CRA group ( 39 ).…”

Non-Invasive Colorectal Cancer Screening: An Overview

“…The use of F. nucleatum together with FIT may improve the detection accuracy for advanced colorectal neoplasia [79]. A most recent report indicated that the combination of F. nucleatum, Clostridium hathewayi, Lachnoclostridium sp., Bacteroides clarus, and FIT presented a high detection accuracy, with a specificity of 81.2% and sensitivity of 93.8% [80].…”