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Background: Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. Results: Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III–IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804–0.873) and 0.857 (95% CI 0.793–0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. Conclusions: This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma. [ABSTRACT FROM AUTHOR]

Objectives: Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery. Methods: Stool samples were collected from 10 children with IgAV (6–14 years old) before and after a multi‐drug therapy, along with 9 age‐matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome. Results: The analyses revealed that compared with healthy controls, treatment‐naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV‐depleted species and 7 IgAV‐elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment‐responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram‐positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV‐depleted bacterial genes, 82 were mainly contributed by gram‐positive bacteria and 12 by gram‐negative bacteria. Conclusions: Gram‐positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease. [ABSTRACT FROM AUTHOR]