Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (4): 619-624. doi: 10.19723/j.issn.1671-167X.2023.04.008

Previous Articles     Next Articles

Relationship between chronic radiation enteritis of cervical cancer and gut microbiota

Hai-hong JIANG1,Xiao-fan LI2,Jian-liu WANG1,*()   

  1. 1. Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Radiation Oncology, Peking University Cancer Hospital, Beijing 100142, China
  • Received:2020-12-24 Online:2023-08-18 Published:2023-08-03
  • Contact: Jian-liu WANG E-mail:wangjianliu1203@163.com
  • Supported by:
    the National Key Technology Research and Development Program of China(2015BAI13B06)

RICH HTML

  

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

CLC Number: 

  • R737.3

Table 1

Questionnaire score and grouping of patients"

Sample number IBDQ Vaizey Clinical information Groups
1 198 9 M
2 184 15 Intestinal dysfunction, chronic diarrhea S
3 138 16 S
4 140 13 S
5 214 4 M
6 166 2 Colonoscopy rectal inflammatory changes, occasionally hematochezia S
7 N N Intestinal dysfunction, chronic diarrhea S
8 155 14 S
9 180 8 S
10 218 1 M
11 150 7 S
12 N N Intestinal dysfunction, chronic diarrhea S
13 207 1 M
14 199 9 M
15 N N Intestinal dysfunction, chronic constipation S
16 104 8 S
17 224 0 M
18 212 1 M
19 215 5 M
20 219 8 M
21 184 13 Intestinal dysfunction, occasional blood in stool S
22 171 13 S
23 195 10 S
24 164 5 S
25 213 0 Intestinal dysfunction, stool 5-6 times a day S
26 200 6 Intestinal dysfunction. CT showed thickened and unsmooth wall of sigmoid colon and rectum S
27 208 11 M
28 216 4 M
29 198 3 M
30 213 12 M
31 172 20 S
32 209 3 M
33 180 5 M
34 215 0 M
Median 198 7
Quartile(more severe direction) 169 12

Figure 1

Comparison of microbial diversity between M group and S group A, comparison of α diversity between group M and group S was shown in boxplot (the middle horizontal line was the median, the upper and lower horizontal lines were the upper and lower quartiles). It could be seen that most of the indicators in group M were higher than that in group S, although there was no significant difference; B, C, PCoA and NMDS analysis of Group M and Group S, it can be intuitively seen the difference in spatial distribution of the two groups (different colors represent different groups, each small dot represents a sample, and the large circle represents confidence ellipse). Faith_pd, Faith's phylogenetic diversity; Pielou_e, Pielou's evenness; M, mild; S, severe; PCoA, principal coordinates analysis; NMDS, nonmetric multidimensional scaling."

Figure 2

Analysis of microbial species differences between M group and S group A, relative abundance of group M and group S at the phylum level; B, relative abundance of group M and group S at the genus level; C, D, LEfSe analysis of group M and group S. Cladogram (C) shows the taxonomic hierarchy of the major taxa from phylum to genus. Histogram (D) shows the logarithmic score values of LDA analysis of each taxon; E, taxonomic hierarchy tree diagram of group M and group S. Large circles with different colors in the figure indicate different taxonomic levels including phylum, class, order, family and genus. It can be intuitively seen the position of microbial species difference between the two groups in each classification grade. M, mild; S, severe; LEFSe, LDA effect size; LDA, linear discriminant analysis."

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
[1] Shengjia PENG,Yu QI,Lijie SUN,Dan LI,Xinyu WANG,Jiangli HAN,Baoxia CHEN,Yuan ZHANG. Afferent baroreflex failure with hyponatremia: A case report [J]. Journal of Peking University (Health Sciences), 2024, 56(2): 357-361.
[2] Xue-ping WANG,Yu-ya-nan ZHANG,Tian-lan LU,Zhe LU,Zhe-wei KANG,Yao-yao SUN,Wei-hua YUE. Variations in fecal microbiota of first episode schizophrenia associated with clinical assessment and serum metabolomics [J]. Journal of Peking University (Health Sciences), 2022, 54(5): 863-873.
[3] Hao WANG,Shu-kun JIANG,Ran PENG,Yi HUANG,Ming-qing WANG,Jun-jie WANG,Cheng LIU,Fan ZHANG,Lu-lin MA. Individual control of urine volume to improve stability of bladder volume in radiotherapy of urinary tumor [J]. Journal of Peking University (Health Sciences), 2020, 52(4): 688-691.
[4] SUN Hai-tao, YANG Rui-jie, JIANG Ping, JIANG Wei-juan, LI Jin-na, MENG Na, WANG Jun-jie. Dosimetric analysis of volumetric modulated arc therapy and intensity modulated radiotherapy for patients undergone breast-conserving operation [J]. Journal of Peking University(Health Sciences), 2018, 50(1): 188-192.
[5] GUO Fu-xin, JIANG Yu-liang, JI Zhe, PENG Ran, SUN Hai-tao, WANG Jun-jie. 3D printed template-assisted and computed tomography image-guided 125-iodine seed implantation for supraclavicular metastatic tumor: a dosimetric study [J]. Journal of Peking University(Health Sciences), 2017, 49(3): 506-511.
[6] LIU Xing-hua, JIANG Xie-yuan, GONG Mao-qi, ZHA Ye-jun. Effect of radiotherapy and indomethacin together in the prevention of recurrence of ectopic ossification around the elbow after resection [J]. Journal of Peking University(Health Sciences), 2016, 48(2): 230-233.
[7] JIANG Ping, ZHOU Shun,WANG Jun-jie, YANG Rui-jie, LIU Zi-yi, JIANG Shu-kun, WANG Wei. Errors in six degree-of-freedom pose estimation of spine tumors assessed by image guided radiotherapy [J]. Journal of Peking University(Health Sciences), 2015, 47(6): 952-956.
[8] WANG Qing-guo, LI Xiao-mei, ZHANG Min, LI Hang, WEN Bing, LI Hong-zhen, GAO Xian-shu. Effect of two dose fractionations on postoperative radiotherapy of keloid: an analysis of 107 patients [J]. Journal of Peking University(Health Sciences), 2014, 46(1): 169-172.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!