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Objective To investigate the effect of Shewanella algae （S.algae） on the occurrence and development of colorectal adenoma and its regulatory effect on the immune microenvironment in mice. Methods Twenty-four mice were divided into three groups： control group， azoxymethane （AOM）/ dextran sodium sulfate （DSS） group， AOM/DSS+S.algae group. The survival status and colorectal adenoma of mice were compared among three groups. Colorectal tissues in the AOM/DSS group and AOM/DSS+S.algae group were collected for high-throughput RNA-seq. Gene set enrichment analysis （GSEA）and cell-type identification by estimating relative subsets of RNA transcripts （CIBERSORT） were used to analyze the changes of immune-related pathways， immune cells and immune factors. Results Compared with the AOM/DSS group， the body weight （P < 0.05） and survival rate were decreased， the hematochezia was aggravated， the survival status was worsened，the colorectal length was shortened （all P < 0.05）， and the average number and size of adenomas were significantly increased （both P < 0.05） in the AOM/DSS+S.algae group. Compared with the AOM/DSS group， the inflammatory responses were significantly enhanced in AOM/DSS+S.algae group （P < 0.05）. The production of pro-inflammatory cytokines including interleukin （IL）-2， IL-6， IL-12， IL-17， interferon （IFN）， tumor necrosis factor （TNF） （all P < 0.05） and IL-1β showed an upward trend in the AOM/DSS+S.algae group， while the production of anti-inflammatory cytokines including IL-4， IL-10， IL-13 （all P < 0.05） and transforming growth factor β showed an inhibitory trend. Both naive B cells and plasma cells （both P < 0.05） were increased in AOM/DSS+S.algae group， and the nuclear factor -κB （NF-κB） signaling pathway was activated. Conclusion S.algae may form a tumor-promoting immune microenvironment by activating immune signals， such as activation of B cells and activation of the NF-κB pathway， and then promote the development of colorectal adenoma.

Gut microbiota dysbiosis contributes to the onset and perpetuation of inflammatory bowel disease (IBD). Given that gut microbiotas vary across geography and ethnicity, it remains obscure whether any universal microbial signatures for IBD diagnosis and prognosis evaluation exist irrespective of populations. Here we profiled the fecal microbiota of a series of Chinese IBD patients and combined them with two Western IBD cohorts, PRISM and RISK, for meta-analyses. We found that the gut microbial alteration patterns in IBD are similar among Chinese and Westerners. Our prediction model based on gut microbiome for IBD diagnosis is robust across the cohorts, which showed 87.5% and 79.1% prediction accuracy in Crohn's disease (CD) and ulcerative colitis (UC) patients, respectively. A relative increase in the levels of Actinobacteria and Proteobacteria (Enterobacteriaceae) and a relative decrease in the levels of Firmicutes (Clostridiales) were strongly correlated with IBD severity (P < 0.05). Additionally, restoration of gut microbiota diversity and a significant increase in Clostridiales relative abundance were found in patients responding to infliximab (IFX [Remicade]) treatment compared to those in relapse. Moreover, certain microbes, mainly Clostridiales, predicted the treatment effectiveness with 86.5% accuracy alone and 93.8% accuracy in combination with calprotectin levels and Crohn's disease activity index (CDAI). Taking the results together, we conclude that gut microbiota can offer a set of universal biomarkers for diagnosis, disease activity evaluation, and infliximab treatment response prediction in IBD. IMPORTANCE In the present report, we show that the human fecal microbiota contains promising and universal biomarkers for the noninvasive evaluation of inflammatory bowel disease severity and IFX treatment efficacy, emphasizing the potential ability to mine the gut microbiota as a modality to stratify IBD patients and apply personalized therapy for optimal outcomes.

Background and Aim: Gastric cancer (GC) is a common malignant neoplasm in the gastrointestinal tract, accounting for high mortality globally. Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar protein, which has been reported to be implicated in the pathogenesis of Treacher Collins syndrome and the development of several types of human cancer. However, the role of TCOF1 in GC is not known. Methods: Immunohistochemistry was carried out to determine TCOF1 expression in GC tissues. Immunofluorescence, co‐IP, and DNA fiber assays were conducted to investigate the function of TCOF1 in GC‐derived BGC‐823 and SGC‐7901 cell lines. Results: TCOF1 expression was aberrantly increased in GC tissues compared with adjacent normal tissues. In addition, we found that TCOF1 left the nucleolus and localized to R‐loops (DNA/RNA hybrids) during S phase in GC cells. Furthermore, TCOF1 interacted with DDX5 and suppressed R‐loop levels. Knockdown of TCOF1 led to increased nucleoplasmic R‐loops specifically during S phase, which restrained DNA replication and cell proliferation. Overexpression of R‐loop eraser RNaseH1 rescued the DNA synthesis defects and decreased DNA damage caused by TCOF1 depletion. Conclusion: These findings demonstrate a novel role of TCOF1 in maintaining GC cell proliferation by alleviating R‐loop associated DNA replication stress. [ABSTRACT FROM AUTHOR]