Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity
From BugSigDB
Jump to:navigation, search
Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Mahdy MS, Azmy AF, Dishisha T, Mohamed WR, Ahmed KA, Hassan A, Aidy SE, El-Gendy AO
Journal
BMC microbiology
Year
2023
Keywords:
Anticancer, Beta-glucuronidase, Colon, Inflammation, Irinotecan, Probiotics
BACKGROUND: Irinotecan is a chemotherapeutic agent used to treat a variety of tumors, including colorectal cancer (CRC). In the intestine, it is transformed into SN-38 by gut microbial enzymes, which is responsible for its toxicity during excretion. OBJECTIVE: Our study highlights the impact of Irinotecan on gut microbiota composition and the role of probiotics in limiting Irinotecan-associated diarrhea and suppressing gut bacterial β-glucuronidase enzymes. MATERIAL AND METHODS: To investigate the effect of Irinotecan on the gut microbiota composition, we applied 16S rRNA gene sequencing in three groups of stool samples from healthy individuals, colon cancer, and Irinotecan treated patients (n = 5/group). Furthermore, three Lactobacillus spp.; Lactiplantibacillus plantarum (L. plantarum), Lactobacillus acidophilus (L. acidophilus), Lacticaseibacillus rhamnosus (L. rhamnosus) were used in a single and mixed form to in-vitro explore the effect of probiotics on the expression of β-glucuronidase gene from E. coli. Also, probiotics were introduced in single and mixed forms in groups of mice before the administration of Irinotecan, and their protective effects were explored by assessing the level of reactive oxidative species (ROS) as well as studying the concomitant intestinal inflammation and apoptosis. RESULTS: The gut microbiota was disturbed in individuals with colon cancer and after Irinotecan treatment. In the healthy group, Firmicutes were more abundant than Bacteriodetes, which was the opposite in the case of colon-cancer or Irinotecan treated groups. Actinobacteria and Verrucomicrobia were markedly present within the healthy group, while Cyanobacteria were noted in colon-cancer and the Irinotecan-treated groups. Enterobacteriaceae and genus Dialister were more abundant in the colon-cancer group than in other groups. The abundance of Veillonella, Clostridium, Butryicicoccus, and Prevotella were increased in Irinotecan-treated groups compared to other groups. Using Lactobacillus spp. mixture in mice models significantly relieved Irinotecan-induced diarrhea through the reduction of both β-glucuronidase expression and ROS, in addition to guarding gut epithelium against microbial dysbiosis and proliferative crypt injury. CONCLUSIONS: Irinotecan-based chemotherapy altered intestinal microbiota. The gut microbiota participates greatly in determining both the efficacy and toxicity of chemotherapies, of which the toxicity of Irinotecan is caused by the bacterial ß-glucuronidase enzymes. The gut microbiota can now be aimed and modulated to promote efficacy and decrease the toxicity of chemotherapeutics. The used probiotic regimen in this study lowered mucositis, oxidative stress, cellular inflammation, and apoptotic cascade induction of Irinotecan.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Subjects
- Location of subjects
- Egypt
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to irinotecan Response to irinotecan,response to irinotecan
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy individuals
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Colon cancer and Irinotecan treated patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with colorectal cancer and Irinotecan treated patients. Irinotecan is a chemotherapeutic agent used to treat a variety of tumors, including colorectal cancer (CRC).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Source: Fig. 4a
Description: The differences in the relative abundance of taxa between the colon cancer patients, Irinotecan treated, and healthy individuals as detected by the linear discriminant analysis effect size (LEfSe)
Abundance in Group 1: decreased abundance in Colon cancer and Irinotecan treated patients
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium | ||
| Bifidobacteriaceae | ||
| Bifidobacteriales | ||
| Gemmiger | ||
| Ruminococcus | ||
| Phascolarctobacterium | ||
| Desulfovibrio | ||
| Desulfovibrionaceae | ||
| Desulfovibrionales | ||
| Muribaculaceae |
Revision editor(s): Scholastica
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy individuals and colon cancer (CRC) patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Irinotecan treated patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients treated with Irinotecan, a chemotherapeutic agent used to treat a variety of tumors, including colorectal cancer (CRC).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 10
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Source: Fig. 4a
Description: The differences in the relative abundance of taxa between the colon cancer patients, Irinotecan treated, and healthy individuals as detected by the linear discriminant analysis effect size (LEfSe)
Abundance in Group 1: increased abundance in Irinotecan treated patients
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus | ||
| Lactobacillaceae | ||
| Lactobacillales | ||
| Butyricicoccus | ||
| Veillonella |
Revision editor(s): Scholastica
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy individuals and Irinotecan treated patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Colon cancer patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with colon cancer
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-18
Source: Fig. 4a
Description: The differences in the relative abundance of taxa between the colon cancer patients, Irinotecan treated, and healthy individuals as detected by the linear discriminant analysis effect size (LEfSe)
Abundance in Group 1: increased abundance in Colon cancer patients
| NCBI | Quality Control | Links |
|---|---|---|
| Dialister | ||
| Enterobacteriaceae | ||
| Enterobacterales |
Revision editor(s): Scholastica
Contents
Retrieved from "https://bugsigdb.org/w/index.php?title=Study_1064&oldid=133247"
