We fed stool samples from patients with CRC and heathy individuals to germ-free mice and conventional mice with azoxymethane. We found stool from patients with CRC to increase the numbers of polyps, levels of intestinal dysplasia and proliferation, markers of inflammation, and proportions of Th1 and Th17 cells in colon, compared with stool from individuals without CRC. This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.

ObjectiveThere is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.DesignWe measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.ResultsThe abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).ConclusionsThis study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.

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We report fluorescent magnetic spore–based microrobots for remote sensing of C. diff toxins in clinical stool supernatants.

Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60% of the world’s population.

No abstract

Incidence of Clostridium difficile infection (CDI) is rapidly increasing and it poses a major health burden globally. However, data regarding the epidemiology of CDI in Asia are limited. We aimed to characterize the antimicrobial susceptibility patterns of common ribotypes of toxigenic C. difficile in Hong Kong. Fifty-three PCR ribotypes were identified among 284 toxigenic C. difficile clinical isolates. The five most prevalent ribotypes were 002 (13%), 017 (12%), 014 (10%), 012 (9.2%), and 020 (9.5%). All tested C. difficile strains remained susceptible to metronidazole, vancomycin, meropenem and piperacillin/tazobactam, but highly resistant to cephalosporins. Of the fluoroquinolones, highest resistance to ciprofloxacin was observed (99%), followed by levofloxacin (43%) and moxifloxacin (23%). The two newly emerged PCR ribotypes, 017 and 002, demonstrated high levels of co-resistance towards clindamycin, tetracycline, erythromycin and moxifloxacin. PCR ribotypes 017 and 002 with multi-drug resistance are rapidly emerging and continuous surveillance is important to monitor the epidemiology of C. difficile to prevent outbreaks of CDI.

Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic APC mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of BRAF or KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.