宫颈癌慢性放射性肠炎与肠道微生物的关系

doi:10.19723/j.issn.1671-167X.2023.04.008

摘要/Abstract

摘要：

目的: 探索宫颈癌慢性放射性肠炎与肠道微生物的关系。方法: 收集34例宫颈癌接受放射治疗至少6个月但不足2年的患者粪便样本，通过临床放射性肠炎诊断、改良的炎症性肠病问卷(inflammatory bowel disease questionnaire，IBDQ)及Vaizey问卷的评估，将患者分为无症状或症状较轻的轻微毒性组(mild，M)和症状较重的严重毒性组(severe，S)。用16S rRNA测序方法对粪便样本提取的DNA进行测序及生物统计学分析，分析指标包括α多样性、β多样性、分类学组成分析、分类等级树图及线性判别分析(linear discriminant analysis, LDA)效应量(LDA effect size, LEfSe)。结果: 从物种多样性来看，M组α多样性大多数指标高于S组，尽管差异没有统计学意义，但是也一定程度地表明了物种多样性低与肠道症状较严重之间的相关性。两组之间β多样性在分布上也存在较大差异，表明两组之间微生物特征的不同。从物种组成来看，在菌门的水平上M组的厚壁菌门[Firmicutes，66.5%(M)vs.56.0%(S)]更高，而变形菌门[Proteobacteria，4.1%(M)vs.13.9%(S)]更低。在菌属的水平上两组之间也存在较大差异，志贺氏菌属(Shigella)2.7%(M)vs.8.5%(S)、粪杆菌属(Faecalibacterium)7.0%(M)vs.2.7%(S)、毛螺菌科-梭菌属(Lachnospiraceae_Clostridium)1.3%(M)vs.4.7%(S)。通过LEfSe也进而发现了一些两组之间差异具有统计学意义的物种，M组中嗜胨菌属(Peptoniphilus)、固氮螺菌属(Azospirillum)、放线菌属(Actinomyces)这些物种丰度显著较高，而在S组中韦荣球菌科(Veillonellaceae)、红杆菌科(Rhodobacteraceae)、红杆菌目(Rhodobacterales)这些物种丰度显著较高。分类等级树图也在空间上直观地表现出了两组在各分类水平物种组成上的差别。结论: 宫颈癌慢性放射性肠炎的严重程度与患者肠道微生物的特征与组成密切相关。

关键词: 宫颈癌, 放射治疗, 慢性放射性肠炎, 肠道微生物

Abstract:

Objective: To explore the relationship between gut microbiota and chronic radiation enteritis of cervical cancer patients. Methods: Fecal samples were collected from 34 patients with cervical cancer who had received radiotherapy for at least 6 months but less than 2 years. The patients were divi-ded into mild toxicity group (mild, M) with no symptoms or mild symptoms and severe toxicity group (severe, S) with severe symptoms by clinical diagnosis of radiation enteritis, modified inflammatory bo-wel disease questionnaire (IBDQ) and Vaizey questionnaire. DNA extracted from fecal samples was sequenced and analyzed by 16S rRNA sequencing method. The analysis indexes included α-diversity, β-diversity, taxonomic composition analysis, taxonomic hierarchy tree and linear discriminant analysis (LDA) effect size (LEfSe). Results: From the perspective of species diversity, most indices of α diversity in group M were higher than those in group S. Although there was no significant difference, it also indicated a correlation between low species diversity and severity of intestinal symptoms to some extent. There was also a significant difference in the distribution of β diversity between the two groups, indicating that the microbial characteristics were different between the two groups. From the perspective of species composition, the M group had higher Firmicutes [66.5% (M) vs. 56.0% (S)] and lower Proteobacteria [4.1% (M) vs. 13.9% (S)] than the S group at the level of phyla. At the level of genus, there were also significant differences between the two groups: Shigella [2.7% (M) vs. 8.5% (S)], Faeca-libacterium [7.0% (M) vs. 2.7% (S)], Lachnospiraceae_Clostridium [1.3% (M) vs. 4.7% (S)]. Through LEfSe also found some species with statistically significant differences between the two groups. The abundance of Peptoniphilus, Azospirillum and Actinomyces in group M was significantly higher, while the abundance of Veillonellaceae, Rhodobacteraceae, and Rhodobacterales in group S was significantly higher. The taxonomic hierarchy tree also intuitively showed the difference in species composition between the two groups at each taxonomic level in space. Conclusion: The severity of chronic radiation enteritis of cervical cancer is closely related to the characteristics and composition of gut microbiota.

Key words: Cervical cancer, Radiotherapy, Chronic radiation enteritis, Gut microbiota

中图分类号:

R737.3

姜海红,李小凡,王建六. 宫颈癌慢性放射性肠炎与肠道微生物的关系[J]. 北京大学学报（医学版）, 2023, 55(4): 619-624.

Hai-hong JIANG,Xiao-fan LI,Jian-liu WANG. Relationship between chronic radiation enteritis of cervical cancer and gut microbiota[J]. Journal of Peking University (Health Sciences), 2023, 55(4): 619-624.

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参考文献 26

1	Andreyev J . Gastrointestinal symptoms after pelvic radiotherapy: A new understanding to improve management of symptomatic patients[J]. Lancet Oncol, 2007, 8 (11): 1007- 1017. doi: 10.1016/S1470-2045(07)70341-8
2	Wang Y , Kong W , Lv N , et al. Incidence of radiation enteritis in cervical cancer patients treated with definitive radiotherapy versus adjuvant radiotherapy[J]. J Cancer Res Ther, 2018, 14 (Suppl 1): 120- 124. doi: 10.4103/0973-1482.163762
3	Jandhyala SM , Talukdar R , Subramanyam C , et al. Role of the normal gut microbiota[J]. World J Gastroenterol, 2015, 21 (29): 8787- 8803. doi: 10.3748/wjg.v21.i29.8787
4	Bäumler AJ , Sperandio V . Interactions between the microbiota and pathogenic bacteria in the gut[J]. Nature, 2016, 535 (7610): 85- 93. doi: 10.1038/nature18849
5	Ma W , Mao Q , Xia W , et al. Gut microbiota shapes the efficiency of cancer therapy[J]. Front Microbiol, 2019, 10, 1050. doi: 10.3389/fmicb.2019.01050
6	Olopade FA , Norman A , Blake P , et al. A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy[J]. Br J Cancer, 2005, 92 (9): 1663- 1670. doi: 10.1038/sj.bjc.6602552
7	Callahan BJ , Mcmurdie PJ , Rosen MJ , et al. Dada2: High-resolution sample inference from illumina amplicon data[J]. Nat Methods, 2016, 13 (7): 581- 583. doi: 10.1038/nmeth.3869
8	Segata N , Izard J , Waldron L , et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol, 2011, 12 (6): 60. doi: 10.1186/gb-2011-12-6-r60
9	Nam YD , Kim HJ , Seo JG , et al. Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing[J]. PLoS One, 2013, 8 (12): e82659. doi: 10.1371/journal.pone.0082659
10	Wang A , Ling Z , Yang Z , et al. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: A pilot study[J]. PLoS One, 2015, 10 (5): e0126312. doi: 10.1371/journal.pone.0126312
11	Wang Z , Wang Q , Wang X , et al. Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy[J]. J Cell Mol Med, 2019, 23 (5): 3747- 3756. doi: 10.1111/jcmm.14289
12	Ferreira MR , Andreyev HJN , Mohammed K , et al. Microbiota and radiotherapy-induced gastrointestinal side-effects(MARS) study: A large pilot study of the microbiome in acute and late radiation enteropathy[J]. Clin Cancer Res, 2019, 25 (21): 6487- 6500. doi: 10.1158/1078-0432.CCR-19-0960
13	Mitra A , Biegert GWG , Delgado AY , et al. Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer[J]. Int J Radiation Oncol Biol Phys, 2020, 107 (1): 163- 171. doi: 10.1016/j.ijrobp.2019.12.040
14	González-Mercado VJ , Henderson WA , Sarkar A , et al. Changes in gut microbiome associated with co-occurring symptoms development during chemo-radiation for rectal cancer: A proof of concept study[J]. Biol Res Nurs, 2021, 23 (1): 31- 41. doi: 10.1177/1099800420942830
15	Cui M , Xiao H , Li Y , et al. Sexual dimorphism of gut microbiota dictates therapeutics efficacy of radiation injuries[J]. Adv Sci, 2019, 6 (21): 1901048. doi: 10.1002/advs.201901048
16	Wang Z , Wang Q , Zhao J , et al. Altered diversity and composition of the gut microbiome in patients with cervical cancer[J]. AMB Expr, 2019, 9 (1): 40. doi: 10.1186/s13568-019-0763-z
17	Sims TT , Colbert LE , Zheng J , et al. Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls[J]. Gynecol Oncol, 2019, 155 (2): 237- 244. doi: 10.1016/j.ygyno.2019.09.002
18	Wang M , Dong Y , Wu J , et al. Baicalein ameliorates ionizing radiation-induced injuries by rebalancing gut microbiota and inhibiting apoptosis[J]. Life Sci, 2020, 261, 118463. doi: 10.1016/j.lfs.2020.118463
19	Ewing LE , Skinner CM , Pathak R , et al. Dietary methionine supplementation exacerbates gastrointestinal toxicity in a mouse model of abdominal irradiation[J]. Int J Radiat Oncol Biol Phys, 2021, 109 (2): 581- 593. doi: 10.1016/j.ijrobp.2020.09.042
20	Lapiere A , Geiger M , Robert V , et al. Prophylactic Faecalibacterium prausnitzii treatment prevents the acute breakdown of colonic epithelial barrier in a preclinical model of pelvic radiation disease[J]. Gut Microbes, 2020, 12 (1): 1- 15.
21	Guo H , Chou WC , Lai Y , et al. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites[J]. Science, 2020, 370 (6516): 9097. doi: 10.1126/science.aay9097
22	Li Y , Yan H , Zhang Y , et al. Alterations of the gut microbiome composition and lipid metabolic profile in radiation enteritis[J]. Front Cell Infect Microbiol, 2020, 10, 541178. doi: 10.3389/fcimb.2020.541178
23	Chitapanarux I , Chitapanarux T , Traisathit P , et al. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients[J]. Radiat Oncol, 2010, 5, 31. doi: 10.1186/1748-717X-5-31
24	Linn YH , Thu KK , Win NHH . Effect of probiotics for the prevention of acute radiation-induced diarrhoea among cervical cancer patients: A randomized double-blind placebo-controlled study[J]. Probiotics Antimicrob Proteins, 2019, 11 (2): 638- 647. doi: 10.1007/s12602-018-9408-9
25	Cui M , Xiao H , Li Y , et al. Faecal microbiota transplantation protects against radiation-induced toxicity[J]. EMBO Mol Med, 2017, 9 (4): 448- 461. doi: 10.15252/emmm.201606932
26	Ding X , Li Q , Li P , et al. Fecal microbiota transplantation: A promising treatment for radiation enteritis?[J]. Radiother Oncol, 2020, 143, 12- 18. doi: 10.1016/j.radonc.2020.01.011

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