Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this stu...Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.展开更多
The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon bi...The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis.Human or mouse colon biopsies were divided into two groups,with one group undergoing host DNA depletion and the other serving as the control.Host DNA was removed through differential lysis of mammalian and bacterial cells before sequencing.The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses.Removing host DNA enhanced bacterial sequencing depth and improved species discovery,increasing bacterial reads by 2.46±0.20 folds while reducing host reads by 6.80%±1.06%.Moreover,2.40 times more of bacterial species were detected after host DNA depletion.This was confirmed from mouse colon tissues,increasing bacterial reads by 5.46±0.42 folds while decreasing host reads by 10.2%±0.83%.Similarly,significantly more bacterial species were detected in the mouse colon tissue upon host DNA depletion(P<0.001).Furthermore,an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues(P<0.001).Our optimized method of host DNA depletion improves the sensitivity of shotgun metagenomic sequencing in bacteria detection in the biopsy,which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.展开更多
基金supported by the National Natural Science Foundation of China(81772850 and 82273300)。
文摘Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.
基金supported by the National Key R&D Program of China(Grant Nos.2020YFA0509200 and 2020YFA0509203)the RGC Theme-based Res Scheme Hong Kong,China(Grant No.T21-705/20-N)+2 种基金the RGC Collaborative Research Fund,China(Grant Nos.C4039-19GF and C7065-18GF)the RGC-GRF Hong Kong,China(Grant No.14163817)the Vice-Chancellor’s Discretionary Fund Chinese University of Hong Kong,China.
文摘The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis.Human or mouse colon biopsies were divided into two groups,with one group undergoing host DNA depletion and the other serving as the control.Host DNA was removed through differential lysis of mammalian and bacterial cells before sequencing.The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses.Removing host DNA enhanced bacterial sequencing depth and improved species discovery,increasing bacterial reads by 2.46±0.20 folds while reducing host reads by 6.80%±1.06%.Moreover,2.40 times more of bacterial species were detected after host DNA depletion.This was confirmed from mouse colon tissues,increasing bacterial reads by 5.46±0.42 folds while decreasing host reads by 10.2%±0.83%.Similarly,significantly more bacterial species were detected in the mouse colon tissue upon host DNA depletion(P<0.001).Furthermore,an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues(P<0.001).Our optimized method of host DNA depletion improves the sensitivity of shotgun metagenomic sequencing in bacteria detection in the biopsy,which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.
