Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma
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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
Hes C, Desilets A, Tonneau M, El Ouarzadi O, De Figueiredo Sousa M, Bahig H, Filion É, Nguyen-Tan PF, Christopoulos A, Benlaïfaoui M, Derosa L, Alves Costa Silva C, Ponce M, Malo J, Belkad W, Charpentier D, Aubin F, Hamilou Z, Jamal R, Messaoudene M, Soulières D, Routy B
Journal
Oral oncology
Year
2023
Keywords:
Chemoradiation therapy, Head and neck squamous cell cancer, Microbiome, Mucositis
OBJECTIVES: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. MATERIALS AND METHODS: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. RESULTS: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. CONCLUSION: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
Experiment 1
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Subjects
- Location of subjects
- Canada
- 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
- Head and neck squamous cell carcinoma carcinoma of the head and neck,craniocervical region squamous cell carcinoma,head and neck squamous cell carcinoma,HNSCC,SCCHN,squamous cell carcinoma of head and neck,squamous cell carcinoma of the head and neck,squamous cell carcinoma, head and neck,squamous cell carcinomas of head and neck,Head and neck squamous cell carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Oral mucositis CTCAE grade 1-2 (mild)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Oral mucositis CTCAE grade 3 (severe)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with severe mucositis following chemoradiation therapy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 30
- Group 1 sample size Number of subjects in the case (exposed) group
- 22
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Fig. 2.
Description: Fig. 2. Gut microbiome profiling with shotgun metagenomic sequencing by development of severe mucositis
Abundance in Group 1: increased abundance in Oral mucositis CTCAE grade 3 (severe)
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Fig. 2
Description: Fig. 2. Gut microbiome profiling with shotgun metagenomic sequencing by development of severe mucositis
Abundance in Group 1: decreased abundance in Oral mucositis CTCAE grade 3 (severe)
Revision editor(s): Andre
Experiment 2
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No enteral feeding plus mild mucositis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Enteral feeding plus mucositis of any grade
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Head and neck squamous cell carcinoma with severe mucositis and enteral feeding need
- Group 0 sample size Number of subjects in the control (unexposed) group
- 27
- Group 1 sample size Number of subjects in the case (exposed) group
- 13
Lab analysis
Statistical Analysis
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Fig 3
Description: Gut microbiome profiling with shotgun metagenomic sequencing by co-occurrence of development of severe mucositis and enteral feeding
Abundance in Group 1: increased abundance in Enteral feeding plus mucositis of any grade
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Fig3.
Description:
Abundance in Group 1: decreased abundance in Enteral feeding plus mucositis of any grade
Revision editor(s): Andre
Experiment 3
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No Enteral feeding tube placement
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Enteral feeding tube placement
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients needing enteral feeding
Lab analysis
Statistical Analysis
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Supplemental Figure 10
Description: Gut microbiome profiling in patients with enteral feeding versus without
Abundance in Group 1: increased abundance in Enteral feeding tube placement
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-4
Source: Supplemental Figure 10
Description: Gut microbiome profiling in patients with enteral feeding versus without
Abundance in Group 1: decreased abundance in Enteral feeding tube placement
Revision editor(s): Andre
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