Novel insights into microbiome in colitis and colorectal cancer

Lü

et al. 2020

Cancers

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme Q tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Queuine is a micronutrient from diet and microbiome. Although tRNA Q-modification has been studied for a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis and the microbiome is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. We also established a QTRT1-knockdown breast MDA-MB-231 cell line. The impacts of QTRT1 deletion or reduction on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using a xenograft BALB/c nude mouse model. We found that QTRT1 deficiency in human breast cancer cells could change the functions of regulation genes, which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo. We identified that several core bacteria, such as Lachnospiraceae, Lactobacillus, and Alistipes, were markedly changed in mice post injection with breast cancer cells. The relative abundance of bacteria in tumors induced from wildtype cells was significantly higher than those of QTRT1 deficiency cells. Conclusions: Our results demonstrate that the QTRT1 gene and tRNA Q-modification altered cell proliferation, junctions, and microbiome in tumors and the intestine, thus playing a critical role in breast cancer development.

Section: Altered Gut Microbiome In the Nude Mice Injected With Wt Mcfmentioning

confidence: 68%

tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors

Lü

et al. 2020

Cancers

“…A meta-analysis of 526 fecal shotgun metagenome datasets identi ed a microbial core of seven enriched bacteria in CRC (22). This core set included: ETBF; four oral bacteria of Fusobacterium nucleatum (35,36), P.micra, Prevotella intermedia (37) and Porphyromonas asaccharolytica (38); and two other bacteria, Thermanaerovibrio acidaminovorans (22) and Alistipes negoldii (39). Yachida et al (23) collected stool samples from 616 participants and found these bacteria were apparent in cases of multiple colorectal adenomas and intramucosal carcinomas.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Fecal Enterotoxigenic Bacteroides fragilis-Peptostreptococcus stomatis-Parvimonas micra Biomarker for Noninvasive Diagnosis and Prognosis of Colorectal Laterally Spreading Tumor

Shen

et al. 2020

Preprint

BackgroudUp to now, non-invasive prediction of laterally spreading tumor (LST) and adenoma recurrence after LST resection is inevitable. The purpose of this study was to identify a microbiome signature with a high predictive effect on LSTs and a microbiome with a high predictive effect on adenoma recurrence after LSTs colectomy.MethodsWe performed 16S rRNA sequencing in mucosal samples with 5 healthy controls (HC), 8 colorectal adenoma (CRA) patients and 11 LST patients. The differentiating microbiota in fecal samples was quantified by qPCR in 475 cases including 113 HC, 208 CRA patients, 109 LST patients and 45 colorectal cancer (CRC) patients. We applied linear discriminant analysis effect size analysis to identify taxa differentially abundant between cases and controls. ROC curve was used to evaluate the diagnostic value of bacterial candidates. Pairwise comparison of AUCs was performed using the Delong's test. Mantel-Haenszel hazard models were used to determine the effects of microbiota composition on recurrence free survival. ResultsLST microbial dysbiosis was characterized by relative high abundance of the genus Bacteroides-Streptococcus and the species enterotoxigenic Bacteroides fragilis (ETBF)-Peptostreptococcus stomatis (P. stomatis)-Parvimonas micra (P. micra). The abundance of ETBF, P. stomatis and P. micra were steadily increasing in LST and CRC groups. P.stomatis behaved stronger value on diagnosis of LST than the other two bacteria (AUC 0.887, 95%CI 0.842-0.931). The combination of P.stomatis, P.micra and ETBF (AUC 0.922, 95%CI 0.887-0.958) revealed strongest diagnostic power with 88.7% sensitivity and 81.4% specificity. ETBF, P. stomatis and P. micra were related to the malignant LST (PP. stomatis=0.0015, PP. micra =0.0255, PETBF =0.0169) and the abundance of IL-6. The relative high-abundance of P. stomatis were related to the adenoma recurrence after LST resection (HR = 3.88, P = 0.008). ConclusionsFecal microbiome signature (ETBF-P. stomatis-P. micra) can diagnose LSTs with high accuracy. ETBF, P. stomatis and P. micra were related to the malignant LST and P.stomatis exhibited a high predictive effect on the adenoma recurrence after endoscopic resection of LSTs. The signature bacteria of LST may provide a noninvasive alternative to early detect LST and predict the adenoma recurrence risk after resections.

“…We also found Lactobacillus decreased in mice with breast cancer cells. In the meantime, we found the abundance change of Alistipes, which may promote digestive diseases, and relatively high incidence in the nipple aspirate fluid from people with breast cancer [23][24][25]. The potential origin of part of breast tissue microbiome may be translocated from the gastrointestinal tract in addition to the skin via the nipple-areolar orifices [44].…”

Section: Discussionmentioning

confidence: 94%

“…The proportions of Lactobacillus, one of the common colonic microbiota, are frequently correlated with intestinal diseases, like Crohn's Disease (CD), obesity, type 2 diabetes and cancer [21], and breast cancer tumor development [22], were found decreased as well. In the meantime, we found the abundance change of Alistipes, which may has disease-promoting activities with gut diseases, and relatively high incidence in the nipple aspirate fluid from people with breast cancer [23][24][25].…”

Section: Altered Gut Microbiome In the Nude Mice Injected With Wt Mcfmentioning

confidence: 90%

tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors

Liu

et al. 2020

Preprint

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme queuine tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Although tRNA Q-modification has been studied a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. The impacts of QTRT1-delection on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using xenograft BALB/c nude mouse model. We found that QTRT1 completely deleted from human breast cancer MCF7 cells could change the functions of regulation genes which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo . We also found that microbiome maybe involved in the breast cancer development in vivo. Conclusions: Our results demonstrate that the QTRT1 gene and microbiome play a critical role in breast cancer development.