乳头状甲状腺癌术后功能减低患者肠道微生物群落的结构性变化
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摘要
目的探索乳头状甲状腺癌(papillary thyroid carcinoma,PTC)术后患者特定病程中的肠道微生物群落的结构性变化。方法纳入64例PTC术后拟行131 I治疗的住院患者为甲癌(thyroid carcinoma,TC)组,同时招募15名健康志愿者作为健康对照(healthy control,HC)组。对TC组及HC组粪便样本用16S rRNA(16S ribosomal RNA)测序法进行微生物组学的分析。将TC组进一步分为合并桥本甲状腺炎(TPOAb>40 IU/mL,TPOAb~+)组和不合并桥本甲状腺炎(TPOAb≤40 IU/mL,TPOAb~-)组,进行微生物组学的分析。结果相比于HC组,TC组患者存在显著的甲状腺功能低下,且TC组粪便微生物群落的丰富度指数显著低于HC组。在属水平上,6种菌群的丰度在两组间具有统计学差异。功能注释分析提示,这些菌群的改变可能与转录因子、膜和胞内结构分子生物合成等相关。TPOAb~+组与TPOAb~-组的粪便微生物群落丰度指数差异无统计学意义。结论与健康人群相比,PTC术后伴随甲状腺功能减低的特定病程中,患者存在肠道微生物群落失调。
Objective To investigate the structural changes of gut microbiota in papillary thyroid carcinoma( PTC) patients with postoperative hypothyroidism. Methods Sixty-four PTC patients reveiving 131 I treatment after PTC thyroidectomy( TC gourp) and 15 healthy subjects( HC group) were recruited in the study. Fecal samples were taken and 16 S ribosomal RNA( 16 S rRNA) sequencing method was used for microbiological analysis. The TC group was further divided into Hashimoto's thyroiditis subgroup( TPOAb > 40 IU/mL,TPOAb~+) and Hashimoto's thyroiditis negative subgroup( TPOAb≤40 IU/mL,TPOAb~-) for microbiological analysis. Results Compared with HC group,TC group had significantly higher rate of hypothyroidism,and the richness index of the gut microbiota in the TC group was significantly lower than that in the HC group. At the genus level,the abundance of the six species was statistically different between the two groups. Functional annotation analysis suggested that changes in these species were associated with transcription factor,membrane and intracellular structural molecule biosynthesis. There was no significant difference in the abundance index of the gut microbiota between the TPOAb~+ group and the TPOAb-group. Conclusion Compared with healthy subjects,there is a gut microbiota imbalance in PTC patients with postoperative hypothyroidism.
Objective To investigate the structural changes of gut microbiota in papillary thyroid carcinoma( PTC) patients with postoperative hypothyroidism. Methods Sixty-four PTC patients reveiving 131 I treatment after PTC thyroidectomy( TC gourp) and 15 healthy subjects( HC group) were recruited in the study. Fecal samples were taken and 16 S ribosomal RNA( 16 S rRNA) sequencing method was used for microbiological analysis. The TC group was further divided into Hashimoto's thyroiditis subgroup( TPOAb > 40 IU/mL,TPOAb~+) and Hashimoto's thyroiditis negative subgroup( TPOAb≤40 IU/mL,TPOAb~-) for microbiological analysis. Results Compared with HC group,TC group had significantly higher rate of hypothyroidism,and the richness index of the gut microbiota in the TC group was significantly lower than that in the HC group. At the genus level,the abundance of the six species was statistically different between the two groups. Functional annotation analysis suggested that changes in these species were associated with transcription factor,membrane and intracellular structural molecule biosynthesis. There was no significant difference in the abundance index of the gut microbiota between the TPOAb~+ group and the TPOAb-group. Conclusion Compared with healthy subjects,there is a gut microbiota imbalance in PTC patients with postoperative hypothyroidism.
引文
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[2]BAS Y,HASSAN H A,ADIGUZEL C,et al.The distribution of cancer cases in Somalia[J].Semin Oncol,2017,44(3):178-186.
[3]GUARNER F,MALAGELADA J R.Gut flora in health and disease[J].Lancet,2003,361(9356):512-519.
[4]SCHIRMER M,FRANZOSA E A,LLOYD-PRICE J,et al.Dynamics of metatranscription in the inflammatory bowel disease gut microbiome[J].Nat Microbiol,2018,3(3):337-346.
[5]DODD D,SPITZER M H,VAN TREUREN W,et al.A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites[J].Nature,2017,551(7682):648-652.
[6]ESPOSITO S,PRINCIPI N.Impact of nasopharyngeal microbiota on the development of respiratory tract diseases[J].Eur J Clin Microbiol Infect Dis,2018,37(1):1-7.
[7]ZHOU L,LI X,AHMED A,et al.Gut microbe analysis between hyperthyroid and healthy individuals[J].Curr Microbiol,2014,69(5):675-680.
[8]KOHLING H L,PLUMMER S F,MARCHESI J R,et al.The microbiota and autoimmunity:their role in thyroid autoimmune diseases[J].Clin Immunol,2017,183:63-74.
[9]LIU Y,YUN X,GAO M,et al.Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in papillary thyroid carcinoma with and without Hashimoto's thyroiditis[J].Clin Transl Oncol,2015,17(4):274-280.
[10]ISHAQ H M,MOHAMMAD I S,SHAHZAD M,et al.Molecular alteration analysis of human gut microbial composition in Graves'disease patients[J].Int J Biol Sci,2018,14(11):1558-1570.
[11]MASETTI G,MOSHKELGOSHA S,KOHLING HL,et al.Gut microbiota in experimental murine model of Graves'orbitopathy established in different environments may modulate clinical presentation of disease[J].Microbiome,2018,6(1):97.
[12]ZHAO F Y,FENG J,LI J,et al.Alterations of the gut microbiota in Hashimoto's thyroiditis patients[J].Thyroid,2018,28(2):175-186.
[13]TAKESHITA K,MIZUNO S,MIKAMI Y,et al.Asingle species of clostridium subcluster XIVa decreased in ulcerative colitis patients[J].Inflamm Bowel Dis,2016,22(12):2802-2810.
[14]PARAMSOTHY S,NIELSEN S,KAMM M A,et al.Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis[J].Gastroenterology,2018.pii:S0016-S5085(18)35387-3.
[15]SOKOL H,LEDUCQ V,ASCHARD H,et al.Fungal microbiota dysbiosis in IBD[J].Gut,2017,66(6):1039-1048.
[16]MAJI A,MISRA R,DHAKAN D B,et al.Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis patients by alteration of butyrate and propionate producers[J].Environ Microbiol,2018,20(1):402-419.
[17]QIN J J,LI Y R,CAI Z M,et al.A metagenomewide association study of gut microbiota in type 2 diabetes[J].Nature,2012,490(7418):55-60
[18]陈桂明,王敏,王建丰,等.甲状腺乳头状癌伴桥本甲状腺炎患者的临床病理特征分析[J].同济大学学报(医学版),2018,39(3):70-73.
[19]ARTHUR J C,GHARAIBEH R Z,MUHLBAUERM,et al.Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer[J].Nat Commun,2014,5:4724.
[20]KOSTIC A D,CHUN E,ROBERTSON L,et al.Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment[J].Cell Host Microbe,2013,14(2):207-215.
[21]ALENGHAT T,ARTIS D.Epigenomic regulation of host-microbiota interactions[J].Trends Immunol,2014,35(11):518-525.
[22]COQUEIRO A Y,RAIZEL R,BONVINI A,et al.Probiotics for inflammatory bowel diseases:a promising adjuvant treatment[J].Int J Food Sci Nutr,2018:1-10.
[23]POSTLER T S,GHOSH S.Understanding the holobiont:how microbial metabolites affect human health and shape the immune system[J].Cell Metab,2017,26(1):110-130.
[24]MA H,YU Y,WANG M M,et al.Correlation between microbes and colorectal cancer:tumor apoptosis is induced by sitosterols through promoting gut microbiota to produce short-chain fatty acids[J].Apoptosis,2019,24(1-2):168-183.
[25]YANO Y,MATSUI T,UNO H,et al.Risks and clinical features of colorectal cancer complicating Crohn's disease in Japanese patients[J].J Gastroenterol Hepatol,2008,23(11):1683-1688.
[26]MEAR J B,GOSSET P,KIPNIS E,et al.Candida albicans airway exposure primes the lung innate immune response against Pseudomonas aeruginosa infection through innate lymphoid cell recruitment and interleukin-22-associated mucosal response[J].Infect Immun,2014,82(1):306-315.
[27]SASSO F C,CARBONARA O,TORELLA R,et al.Ultrastructural changes in enterocytes in subjects with Hashimoto's thyroiditis[J].Gut,2004,53(12):1878-1880.
[28]MU Q H,KIRBY J,REILLY C M,et al.Leaky gut as a danger signal for autoimmune diseases[J].Front Immunol,2017,8:598.
[29]ZHANG L X,CHEN J Y,XU C Y,et al.Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17cells of patients with differentiated thyroid carcinoma[J].Exp Ther Med,2018,15(3):2661-2666.
[30]KANG H J,IM S H.Probiotics as an immune modulator[J].J Nutr Sci Vitaminol,2015,61(Suppl):S103-S105.
[31]KULKARNI N,REDDY B S.Inhibitory effect of bifidobacterium iongum cultures on the azoxymethaneinduced aberrant crypt foci formation and fecal bacterialglucuronidase[J].Proc Soc Exp Biol Med,1994,207(3):278-283.
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