Distinct microbes, metabolites, and the host genome define the multi-omics profiles in right-sided and left-sided colon cancer.

IF 13.8 1区生物学 Q1 MICROBIOLOGY Microbiome Pub Date : 2024-12-28 DOI:10.1186/s40168-024-01987-7

Lei Liang, Cheng Kong, Jinming Li, Guang Liu, Jinwang Wei, Guan Wang, Qinying Wang, Yongzhi Yang, Debing Shi, Xinxiang Li, Yanlei Ma

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Abstract

Background: Studies have reported clinical heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). However, none of these studies used multi-omics analysis combining genetic regulation, microbiota, and metabolites to explain the site-specific difference.

Methods: Here, 494 participants from a 16S rRNA gene sequencing cohort (50 RCC, 114 LCC, and 100 healthy controls) and a multi-omics cohort (63 RCC, 79 LCC, and 88 healthy controls) were analyzed. 16S rRNA gene, metagenomic sequencing, and metabolomics analyses of fecal samples were evaluated to identify tumor location-related bacteria and metabolites. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) were conducted to obtain the mutation burden and genomic expression pattern.

Results: We found unique profiles of the intestinal microbiome, metabolome, and host genome between RCC and LCC. The bacteria Flavonifractor plautii (Fp) and Fusobacterium nucleatum, the metabolites L-phenylalanine, and the host genes PHLDA1 and WBP1 were the key omics features of RCC; whereas the bacteria Bacteroides sp. A1C1 (B.A1C1) and Parvimonas micra, the metabolites L-citrulline and D-ornithine, and the host genes TCF25 and HLA-DRB5 were considered the dominant omics features in LCC. Multi-omics correlation analysis indicated that RCC-enriched Fp was related to the accumulation of the metabolite L-phenylalanine and the suppressed WBP1 signal in RCC patients. In addition, LCC-enriched B.A1C1 was associated with the accumulation of the metabolites D-ornithine and L-citrulline as well as activation of the genes TCF25, HLA-DRB5, and AC079354.1.

Conclusion: Our findings identify previously unknown links between intestinal microbiota alterations, metabolites, and host genomics in RCC vs. LCC, suggesting that it may be possible to treat colorectal cancer (CRC) by targeting the gut microbiota-host interaction. Video Abstract.

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不同的微生物、代谢物和宿主基因组定义了右侧和左侧结肠癌的多组学特征。

背景：研究报道了右侧结肠癌（RCC）和左侧结肠癌（LCC）的临床异质性。然而，这些研究都没有使用结合遗传调控、微生物群和代谢物的多组学分析来解释位点特异性差异。方法：本研究对来自16S rRNA基因测序队列（50名RCC， 114名LCC和100名健康对照）和多组学队列（63名RCC， 79名LCC和88名健康对照）的494名参与者进行了分析。对粪便样本进行16S rRNA基因、宏基因组测序和代谢组学分析，以鉴定与肿瘤位置相关的细菌和代谢物。采用全外显子组测序（WES）和转录组测序（RNA-seq）获得突变负荷和基因组表达模式。结果：我们发现了RCC和LCC之间肠道微生物组、代谢组和宿主基因组的独特特征。细菌多黄酮因子（Fp）和核梭杆菌、代谢产物l -苯丙氨酸和宿主基因PHLDA1和WBP1是RCC的关键组学特征；而拟杆菌（Bacteroides sp. A1C1）和微细小单胞菌（Parvimonas micra）、代谢产物l -瓜氨酸和d -鸟氨酸以及宿主基因TCF25和HLA-DRB5被认为是LCC的主要组学特征。多组学相关分析表明，RCC富集的Fp与RCC患者代谢产物l -苯丙氨酸的积累和WBP1信号的抑制有关。此外，富含lcc的B.A1C1与代谢产物d -鸟氨酸和l -瓜氨酸的积累以及TCF25、HLA-DRB5和AC079354.1基因的激活有关。结论：我们的研究结果确定了RCC与LCC中肠道微生物群改变，代谢物和宿主基因组学之间先前未知的联系，这表明可能通过靶向肠道微生物-宿主相互作用来治疗结直肠癌（CRC）。视频摘要。

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来源期刊

Microbiome MICROBIOLOGY-

CiteScore

21.90

自引率

2.60%

发文量

198

审稿时长

4 weeks

期刊介绍： Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.