Postoperative Probiotics Administration Attenuates Gastrointestinal Complications and Gut Microbiota Dysbiosis Caused by Chemotherapy in Colorectal Cancer Patients
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Study information
incomplete
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Huang F, Li S, Chen W, Han Y, Yao Y, Yang L, Li Q, Xiao Q, Wei J, Liu Z, Chen T, Deng X
Journal
Nutrients
Year
2023
Keywords:
CRC, chemotherapy, gastrointestinal complications, gut microbiota, probiotics
The current study aims to evaluate the potential roles of taking probiotics postoperatively in attenuating the gastrointestinal complications and disturbed gut microbiota in colorectal cancer (CRC) patients undergoing chemotherapy. One hundred eligible CRC patients who were treated with radical surgery and needed to receive chemotherapy were recruited. Half of them were randomly assigned to the Probio group to take a probiotic combination from post-operation to the end of the first chemotherapeutic course. The other half of patients taking placebo instead were classified as the Placebo group. Gastrointestinal complications such as nausea, acid reflux, abdominal pain, abdominal distention, constipation, and diarrhea were recorded during chemotherapy. Fecal samples were collected preoperatively and after the first cycle of postoperative chemotherapy for 16S rRNA high-throughput sequencing and short-chain fatty acids (SCFAs) analysis. Results showed that probiotics administration could effectively reduce chemotherapy-induced gastrointestinal complications, particularly in diarrhea (p < 0.01). Additionally, chemotherapy also reduced the bacterial diversity indexes of the gut microbiota in CRC patients, which could be significantly increased by taking probiotics. Moreover, this chemotherapy caused significant changes in the composition of the gut microbiota, as indicated by decreased phylum levels of Firmicutes and increased Bacteroidetes, Proteobacteria, and Verrucomicrobia. In particular, several bacterial genera such as Akkermansia and Clostridium were significantly increased, while Prevotella, Lactobacillus, and Roseburia were decreased (p < 0.05). However, probiotic administration could effectively restore these taxa changes both at the phylum and genus levels, and mildly increase the genus levels of Bifidobacterium, Streptococcus, and Blautia. Furthermore, probiotics could also promote the production of SCFAs, particularly increasing acetate, butyrate, and propionate (p < 0.0001). These results support the beneficial effects of the probiotic interventions as novel alternative or complementary strategies in chemoprevention.
Statistical test
Kruskall-Wallis Dunn's test
Experiment 1
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces , Blood 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,Portion of blood,Vertebrate blood,Whole blood,Blood
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- chemotherapy-induced gastrointestinal mucositis , colorectal cancer chemo-induced gut toxicity,chemotherapy-induced gut toxicity,chemotherapy-induced gut toxicity (CIGT),chemotherapy-induced mucositis (CIM),chemotherapy-induced gastrointestinal mucositis,cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CRC (colorectal cancer patients)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Placebo
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who received radical surgery and went through first chemotherapy course. This group was instructed to take placebo tablets orally according to the scheme 1 × 3 tablets (one capsule at a time and three times per day) from the third postoperative day to the end of the first chemotherapy course (Capecitabine + Oxaliplatin, XELOX regimen).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 50
- Group 1 sample size Number of subjects in the case (exposed) group
- 50
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- N/A
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- 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
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, Confounders controlled for: "gender" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gender, Confounders controlled for: "tumor category" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.tumor category, Confounders controlled for: "node category" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.node category
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 2
Source: Figure 3 g,h,i
Description: relative abundance
Abundance in Group 1: decreased abundance in Placebo
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Lactobacillus | ||
| Roseburia |
Revision editor(s): Yjung24
Experiment 2
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Probio
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who received radical surgery and went through first chemotherapy course. This group was instructed to take probiotic tablets orally according to the scheme 1 × 3 tablets (one capsule at a time and three times per day) from the third postoperative day to the end of the first chemotherapy course (Capecitabine + Oxaliplatin, XELOX regimen).
Lab analysis
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V4
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Placebo
Lab analysis
Statistical Analysis
- Statistical test
- Kruskall-Wallis
- LEfSe
- Dunn's test
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Source: Figure 3 h,i,j
Description: relative abundance
Abundance in Group 1: increased abundance in Probio
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus | ||
| Roseburia | ||
| Blautia |
Revision editor(s): Yjung24
Experiment 4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CRC (colorectal cancer patients)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Placebo
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who received radical surgery and went through first chemotherapy course. This group was instructed to take placebo tablets orally according to the scheme 1 × 3 tablets (one capsule at a time and three times per day) from the third postoperative day to the end of the first chemotherapy course (Capecitabine + Oxaliplatin, XELOX regimen).
Lab analysis
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
Statistical Analysis
- Statistical test
- LEfSe
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 1
Source: Figure 4
Description: LEFSe analysis LDA threshold = 2
Abundance in Group 1: decreased abundance in Placebo
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridia | ||
| Lactobacillaceae | ||
| Roseburia | ||
| Phascolarctobacterium | ||
| Lactobacillus | ||
| Desulfovibrio |
Revision editor(s): Yjung24
Signature 2
Source: Figure 4
Description: LEFSe Analysis, LDA threshold = 2
Abundance in Group 1: increased abundance in Placebo
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Enterococcaceae | ||
| Enterococcus | ||
| Clostridium | ||
| Parabacteroides | ||
| Ruminococcus |
Revision editor(s): Yjung24
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Placebo
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Probio
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who received radical surgery and went through first chemotherapy course. This group was instructed to take probiotic tablets orally according to the scheme 1 × 3 tablets (one capsule at a time and three times per day) from the third postoperative day to the end of the first chemotherapy course (Capecitabine + Oxaliplatin, XELOX regimen).
Lab analysis
Statistical Analysis
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Source: Figure 4
Description: LEFSe Analysis, LDA threshold = 2
Abundance in Group 1: decreased abundance in Probio
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Enterococcaceae | ||
| Enterococcus | ||
| Parabacteroides | ||
| Ruminococcus |
Revision editor(s): Yjung24
Signature 2
Source: Figure 4
Description: LEFSe Analysis, LDA threshold = 2
Abundance in Group 1: increased abundance in Probio
| NCBI | Quality Control | Links |
|---|---|---|
| Microbispora rosea subsp. rosea | ||
| Haemophilus | ||
| Alistipes | ||
| Gemmiger | ||
| Rikenellaceae | ||
| Clostridiaceae |
Revision editor(s): Yjung24
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