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

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

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

All patients will filled validated questionnaires and 4-days food diary. They will also have a urinary permeability test (lactulose/mannitol test) and collected stools samples for microbiota analysis.

Inclusion Criteria:

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
  • Woman of childbearing age with effective contraception for the duration of the study such as oestroprogestins, intrauterine device, tubal ligation, vasectomised partner or sexual abstinence (no heterosexual intercourse for 1 month and a negative urine pregnancy test at inclusion).
  • Postmenopausal women: confirmatory diagnosis (non-medically induced amenorrhoea for at least 12 months prior to the inclusion visit or biologically documented)
  • 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):

• 25g 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
• Rectal barostat finding visceral hypersensitivity

For the IBS group without fructose malabsorption or visceral hypersensitivity (called the NormoF-NormoSens group) (4):

• Fructose breath test at a dose of 25g in favour of the absence of fructose malabsorption
• Rectal barostat finding no visceral hypersensitivity

Exclusion Criteria:

• 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)

• Systemic antibiotic use (oral, IV or IM) in the month prior to inclusion

• 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.