Chemotherapy-driven intestinal dysbiosis and microbial indole-3-propionic acid rewire bone marrow myelopoiesis to promote anti-metastatic immunity [16S rRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE296900 | GEO | 2025/10/22
REPOSITORIES: GEO
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Project description:Chemotherapy-driven intestinal dysbiosis and microbial indole-3-propionic acid rewire bone marrow myelopoiesis to promote anti-metastatic immunity [16S rRNA-Seq]
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Project description:As research focusing on the colorectal cancer fecal microbiome using shotgun sequencing continues, increasing evidence has supported correlations between colorectal carcinomas (CRCs) and fecal microbiome dysbiosis. However, large-scale on-site and off-site (surrounding adjacent) tissue microbiome characterization of CRC was underrepresented. Here, considering each taxon as a feature, we demonstrate a machine learning-based method to investigate tissue microbial differences among CRC, colorectal adenoma (CRA), and healthy control groups using 16S rRNA data sets retrieved from 15 studies. A total of 2,099 samples were included and analyzed in case-control comparisons. Multiple methods, including differential abundance analysis, random forest classification, cooccurrence network analysis, and Dirichlet multinomial mixture analysis, were conducted to investigate the microbial signatures. We showed that the dysbiosis of the off-site tissue of colonic cancer was distinctive and predictive. The AUCs (areas under the curve) were 80.7%, 96.0%, and 95.8% for CRC versus healthy control random forest models using stool, tissue, and adjacent tissue samples and 69.9%, 91.5%, and 89.5% for the corresponding CRA models, respectively. We also found that the microbiota ecologies of the surrounding adjacent tissues of CRC and CRA were similar to their on-site counterparts according to network analysis. Furthermore, based on the enterotyping of tissue samples, the cohort-specific microbial signature might be the crux in addressing classification generalization problems. Despite cohort heterogeneity, the dysbiosis of lesion-adjacent tissues might provide us with further perspectives in demonstrating the role of the microbiota in colorectal cancer tumorigenesis.IMPORTANCE Turbulent fecal and tissue microbiome dysbiosis of colorectal carcinoma and adenoma has been identified, and some taxa have been proven to be carcinogenic. However, the microbiomes of surrounding adjacent tissues of colonic cancerous tissues were seldom investigated uniformly on a large scale. Here, we characterize the microbiome signatures and dysbiosis of various colonic cancer sample groups. We found a high correlation between colorectal carcinoma adjacent tissue microbiomes and their on-site counterparts. We also discovered that the microbiome dysbiosis in adjacent tissues could discriminate colorectal carcinomas from healthy controls effectively. These results extend our knowledge on the microbial profile of colorectal cancer tissues and highlight microbiota dysbiosis in the surrounding tissues. They also suggest that microbial feature variations of cancerous lesion-adjacent tissues might help to reveal the microbial etiology of colonic cancer and could ultimately be applied for diagnostic and screening purposes.
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Project description:The ruminant gut microbial community has a strong impact on host health and can be altered during diarrhea disease. As an indigenous breed of the Tibetan Plateau, domestic yak displays a high diarrhea rate, but little research has been done to characterize the bacterial microbial structure in diarrheic yaks. In the present study, a total of 30 adult yaks, assigned to diarrhea (case, N = 15) and healthy (control, N = 15) groups, were subjected to gut microbiota profiling using the V3-V4 regions of the 16S rRNA gene. The results showed that the gut microbiome of the case group had a significant decrease in alpha diversity. Additionally, differences in beta diversity were consistently observed for the case and control groups, indicating that the microbial community structure was changed due to diarrhea. Bacterial taxonomic analysis indicated that the Bacteroidetes, Firmicutes, and Proteobacteria were the three most dominant phyla in both groups but different in relative abundance. Especially, the proportion of Proteobacteria in the case group was increased as compared with the control group, whereas Spirochaetota and Firmicutes were significantly decreased. At the genus level, the relative abundance of Escherichia-Shigella and Prevotellaceae_UCG-003 were dramatically increased, whereas that of Treponema, p-2534-18B5_gut_group, and Prevotellaceae_UCG-001 were observably decreased with the effect of diarrhea. Furthermore, based on our linear discriminant analysis (LDA) effect size (LEfSe) results, Alistipes, Solibacillus, Bacteroides, Prevotellaceae_UCG_003, and Bacillus were significantly enriched in the case group, while the other five genera, such as Alloprevotella, RF39, Muribaculaceae, Treponema, and Enterococcus, were the most preponderant in the control group. In conclusion, alterations in gut microbiota community composition were associated with yak diarrhea, differentially represented bacterial species enriched in case animals providing a theoretical basis for establishing a prevention and treatment system for yak diarrhea.
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