Association Between Composition of the Gut Microbiota and Nutritional Status in Digestive Oncology

Official title

Study of the Association Between the Composition of the Gut Microbiota and Nutritional Status in Patients Treated With Chemotherapy in Digestive Oncology

Overview

Nutritional status represents a crucial issue in the management of cancer patients, as between 40% and 60% of them suffer from malnutrition at the time of diagnosis. This condition worsens morbidity, increases treatment-related adverse effects, infections, and hospitalizations, and can lead to death in 10% to 20% of cases, independently of tumor progression. Anticancer treatments often exacerbate malnutrition due to their side effects, such as loss of appetite or taste alterations. Although international guidelines (ESPEN, ESMO, ASCO) recommend a multimodal nutritional intervention combining nutritional support and physical activity. The effectiveness of these approaches varies among patients. This variability can be explained by several factors, including individual differences in dietary intake response, metabolic status, and digestive tolerance to treatments. The intestinal and oral microbiota appear to be key cofactors in regulating these various parameters, influencing appetite, host metabolism, and intestinal absorption. Alterations in the microbiota-particularly a decrease in bacterial diversity and an increase in Candida albicans-have been associated with appetite loss and taste perception disorders, especially in patients with digestive cancers. Therefore, the intestinal microbiota constitutes a potential therapeutic and diagnostic target to improve nutritional strategies in oncology. Interventions targeting the microbiota (such as probiotic supplementation or fecal microbiota transplantation) have already demonstrated an impact on nutritional parameters in preclinical models of malnourished cancer-bearing mice; however, clinical data remain scarce and limited. The ONCONUTRIBIOTA-cohort study aims to characterize and investigate the oral and intestinal microbiota of patients initiating chemotherapy for digestive cancer, in relation to their nutritional status clinical characteristics and food preferences, in order to identify potential biomarkers or therapeutic targets to optimize their nutritional management. Patients will be followed during two of their routine care visits: on the day of the first chemotherapy treatment and at the end of the first cycle of chemotherapy. During these visits, stool and saliva samples will be collected, completed by additional assessments including global quality of life and nutritional quality of life questionnaires, olfactory and gustatory tests, and measurements of parameters used to determine the presence of malnutrition, general health status and oncological evaluation.

Interventions

• Other Not applicable- observational study
  During two routine care visits - on the day of the first chemotherapy administration and at the end of the first chemotherapy cycle - stool and saliva samples will be collected. These will be complemented by additional assessments, including global and nutritional quality of life questionnaires, olfactory and gustatory tests, and measurements of parameters related to malnutrition, general health status, and oncological evaluation (including blood sampling and specific analyses based on the radio

Primary outcome measures

• Difference in fecal microbiota composition, assessed by beta-diversity (Weighted UniFrac and Bray-Curtis) based on shotgun metagenomic data, between patients with severe, moderate, or no malnutrition evaluated at V1 and V2. [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]

Secondary outcome measures (12)

• Difference in oral microbiota composition before and after chemotherapy treatment [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Variation in the taxonomic and functional composition of the oral and fecal microbiota [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Fecal and oral metabolomic signatures associated with malnutrition status [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation between taxonomic profiles and markers of nutritional status [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Change in nutritional parameters during chemotherapy [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Intra-individual variation in blood markers of nutritional status [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Change in sensory scores during chemotherapy [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation between sensory scores and nutritional status markers [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation between sensory scores and the composition of oral and fecal microbiota [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation of patients' quality of life with the composition of oral and fecal microbiota [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation between sensory scores and quality of life score [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]
• Correlation between nutritional status markers and quality of life score [Time frame: at pre-chimotherapy or after the 1st chimotherapy treatment and the end of the first cycle of chemotherapy]

Eligibility criteria

• Inclusion Criteria \* :
• Adult patient
• Patient with digestive cancer, including:

• Borderline or locally advanced pancreatic adenocarcinoma
• Metastatic pancreatic adenocarcinoma without symptomatic peritoneal carcinomatosis
• metastatic colon/rectal cancer without symptomatic peritoneal carcinomatosis
• Patients with an indication for chemotherapy (induction treatment or treatment of metastatic disease)
• Patients able to eat orally at the time of inclusion in the study
• Patients with a performance status (PS) score ≤2
• Patients who agree to provide stool and saliva samples
• Patients who have given their written informed consent
• Patients affiliated with the French social security system
• Exclusion Criteria :
• Pregnant or breastfeeding women
• Patients who have received antibiotics within 3 weeks prior to the first chemotherapy treatment (excluding antibiotic prophylaxis administered in the context of surgery or endoscopy).
• Individuals receiving psychiatric care that may interfere with their ability to respond to questionnaires (in the investigator's opinion)
• Persons deprived of their liberty or subject to legal protection measures (guardianship, curatorship)
• Patients participating in another interventional study with medication
• Patients who have undergone chemotherapy for another malignant tumor in the last 12 months.
• Patients with another synchronous malignant tumor, with the exception of adequately treated carcinoma in situ of the cervix or squamous cell carcinoma of the skin, or limited basal cell or squamous cell skin cancer. This cancer must then be adequately controlled.
• Patients with symptomatic brain and/or meningeal metastases.
• Patients who have undergone digestive resection (excluding appendectomy or cholecystectomy >12 months ago).
• Patients with symptomatic peritoneal carcinomatosis prior to the start of chemotherapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 3 centers

• Edouard Herriot Hospital - medical oncology department — Lyon
• Croix Rousse Hospital Hepatology and Gastroenterology Department — Lyon
• Lyon Sud Hospital - Hepatology and Gastroenterology Department — Lyon

Identifiers

NCT: NCT07260617 · 69HCL25_0613 · 2025-A02021-48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗