New Microbiota-endocrine Axis in Fructose Malabsorption-caused Visceral Hypersensitivity in Irritable Bowel Syndrome.

NCT07337707 | Not Yet Recruiting

• 1 other identifier: 2023/0252/HP
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Irritable bowel syndrome (IBS) affects around 4% of the general population and remains the most common functional bowel disorder. It is defined by the Rome criteria as the presence of abdominal pain associated with transit disorders. The impact on quality of life and the associated costs make it a public health problem. Visceral hypersensitivity is one of the functional markers of the disease and plays a part in the genesis of symptoms. It could therefore also be a therapeutic target to be explored. Diet and the intestinal microbiota are also part of the recognised pathophysiological mechanisms of this disease. Carbohydrates malabsorbed by the intestine are metabolised by the microbiota, which may contribute to the genesis of symptoms. Among these carbohydrates, fructose appears to be of particular interest. Its absorption capacity is limited, yet fructose consumption is increasing. Fructose malabsorption at a dose of 25 g is present in 22% of IBS patients. Fructose malabsorption is also associated with visceral hypersensitivity. However, the mechanism of this association remains unknown. In models of malabsorbed mice with visceral hypersensitivity, an increase in cholecystokinin was found in the terminal ileum and cecum, suggesting a potential role for this hormone in this model of IBS. However, the underlying mechanism remains poorly understood. The objective is to determine if microbiota signature is specific of visceral hypersensitivity associated with fructose malabsorption in IBS patients. 60 patients with IBS will be included in the study in 4 groups:

1. 1.n=15 patients with visceral hypersensitivity and fructose malabsorption
2. 2.n=15 patients with visceral hypersensitivity and without fructose malabsorption
3. 3.n=15 patients without visceral hypersensitivity and with fructose malabsorption
4. 4.n=15 patients without visceral hypersensitivity and without fructose malabsorption

Conditions

Irritable Bowel Syndrome (IBS)

Keywords

visceral hypersensitivity; fructose malabsorption; microbiota

Outcome Measures

Primary Outcomes (2)

• microbiota analysis

  16S RNA gene sequencing

  from enrollment up to 18 months

• metabolites analysis

  Mass spectrometry-based metabolomics

  from enrollment up to 18 months

Secondary Outcomes (8)

• Intestinal permeability

  from enrollment up to 18 months

• low grade inflammation

  from enrollment up to 18 months

• fructose consumption

  from enrollment up to 18 months

• IBS severity

  from enrollment up to 18 months

• Stool consistency

  from enrollment up to 18 months

Study Arms (4)

MalF-HyperSens

EXPERIMENTAL

Patients with IBS with fructose malabsorption and with visceral hypersensitivity

Biological: urine intestinal permeability test or lactulose/mannitol test; Biological: Blood test; Other: food diary; Other: stool samples; Other: Microbiota analysis

MalF-NormoSens

EXPERIMENTAL

Patients with IBS with fructose malabsorption and without hypersensitivity

Biological: urine intestinal permeability test or lactulose/mannitol test; Biological: Blood test; Other: food diary; Other: stool samples; Other: Microbiota analysis

NormoF-HyperSens

EXPERIMENTAL

Patients with IBS without fructose malabsorption and with visceral hypersensitivity

Biological: urine intestinal permeability test or lactulose/mannitol test; Biological: Blood test; Other: food diary; Other: stool samples; Other: Microbiota analysis

NormoF-NormoSens

EXPERIMENTAL

Patients with IBS without fructose malabsorption and without visceral hypersensitivity

Biological: urine intestinal permeability test or lactulose/mannitol test; Biological: Blood test; Other: food diary; Other: stool samples; Other: Microbiota analysis

Interventions

food diary OTHER

On the day of inclusion, all patients were given a food diary to fill in. They will have to fill it in over a period of 4 days, including 1 weekend day. They will be asked to note down all the food they eat during this period, as well as the quantities. The diary will be collected at the V1 visit and will then be analysed by a dietician, who will assess the average daily consumption of fructose in g/d (total fructose consumption, consumption of fructose in excess of glucose, dietary origin of fructose).

MalF-HyperSens; MalF-NormoSens; NormoF-HyperSens; NormoF-NormoSens

stool samples OTHER

All patients will have their stools collected. Patients will have their stool collected at home using a collector given to them at the inclusion visit. They will have to bring back the stool within 6 hours for preparation and storage at -80°C.

MalF-HyperSens; MalF-NormoSens; NormoF-HyperSens; NormoF-NormoSens

Microbiota analysis OTHER

Stools will be used to analyse the composition of the intestinal microbiota by sequencing amplicons from the V3-V4 region of bacterial 16S rRNA.

MalF-HyperSens; MalF-NormoSens; NormoF-HyperSens; NormoF-NormoSens

urine intestinal permeability test or lactulose/mannitol test BIOLOGICAL

Patients will be required to fast for 12 hours and, after emptying their bladder, patients will be asked to drink 100 mL of water containing 10 g of lactulose and 5 g of mannitol. At the patient's inclusion visit, and before the test at the V1 follow-up visit, the patient will be given an explanation with recommendations on their food intake in the 24 hours before and 24 hours during the test (urine collection). Patients will be asked not to drink for 2 hours and not to eat for 5 hours after taking the lactulose and mannitol. An exhaustive urine collection will then be carried out at the patient's home over the 24 hours following the intake of the sugars. The 24-hour urine will be collected in a plastic 24-hour urine container suitable for hospital use. This urine collection will be brought back for visit 2 the following day. On receipt of the urine, the volume of urine will be noted and the appearance of the urine recorded and stored before analysis.

MalF-HyperSens; MalF-NormoSens; NormoF-HyperSens; NormoF-NormoSens

Blood test BIOLOGICAL

A fasting blood sample will be taken in 1 x 4ml EDTA-Aprotinin tube on the morning of the urine test (V1 follow-up visit). The tube will be centrifuged within 15 minutes at 4°C and then aliquoted into 3 x 500μL tubes which will be immediately frozen at -80°C for storage in a biocollection with a view to later measuring gastrointestinal peptides such as CCK, neurotensin and GLP-1.

MalF-HyperSens; MalF-NormoSens; NormoF-HyperSens; NormoF-NormoSens

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all groups:
• Patients with IBS defined by current Rome criteria (currently IV)
• Adult, aged 18 to 75
• Regulatory criteria :
• Membership of a social security scheme
• Adult having read and understood the information letter and signed the consent form
• Women of childbearing age who have been rendered surgically infertile (e.g. hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
• For the IBS group with fructose malabsorption and visceral hypersensitivity (named group of interest, MalF-HyperSens) (1):
• g fructose breath test in favour of fructose malabsorption
• Rectal barostat finding visceral hypersensitivity
• For the IBS group with fructose malabsorption and without visceral hypersensitivity (known as the MalF-NormoSens group) (2):
• Fructose breath test at 25g dose in favour of fructose malabsorption
• Rectal barostat finding no visceral hypersensitivity
• For the IBS group without fructose malabsorption and visceral hypersensitivity (named NormoF-HyperSens group) (3):
• Fructose breath test at 25g dose in favour of no fructose malabsorption

You may not qualify if:

• Patient who has not undergone a fructose breath test or a barostat in our department in the last 10 years.
• Patient with organic digestive pathology (chronic inflammatory bowel disease, microscopic colitis, digestive cancer, celiac disease)
• Regulatory criteria :
• Pregnant or parturient or breast-feeding woman or proven absence of contraception,
• Person deprived of liberty by an administrative or judicial decision or person placed under court protection / sub- guardianship or curatorship,
• Person undergoing research participating in another trial / having participated in another trial within a period of 2 weeks,
• History of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol or preventing him/her from giving informed consent.

Sponsors & Collaborators

• University Hospital, Rouen: lead
• ANR AAPG2023: collaborator
• INRAE-Micalis AMIPEM: collaborator
• INRAE-Micalis FINE: collaborator

Study Sites (1)

CHU de Rouen

Rouen, France

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome; Fructose Intolerance

Interventions

Lactulose; Hematologic Tests; Diet Records

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Fructose Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Records; Organization and Administration; Health Services Administration

Study Officials

• MELCHIOR Pr MELCHIOR

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chloé MELCHIOR, PUPH

CONTACT

+332 32 88 67 07; chloe.melchior@chu-rouen.fr

Mylene HERVET

CONTACT

mylene.hervet@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: January 13, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)