PROfiles of FGF-19 Post-prandial Secretion in Older Adults With Frailty and Without Frailty

Fibroblast Growth Factor 19 (FGF-19) is an intestinal hormone secreted in the post-prandial state, whose primary role is to inhibit bile acid synthesis in the liver. It is expressed by the FXR (Farnesoid X receptor) nuclear receptor in the enterocytes of the ileum, which is activated by specific bile acids metabolized in the gut microbiota. It was demonstrated that treatment with FGF-19 induces myofiber hypertrophy in vitro and increases muscle strength and mass in mice model of sarcopenia. Sarcopenia and the commonly associated physical frailty, are age-related syndromes associated with adverse events (such as falls and fractures, mobility disability) and increased mortality. Currently, there is no drug treatment that has been proven effective to counteract those syndromes and standard care consists in non-pharmacological interventions (exercise and nutrition) whose implementation remains complex due to several barriers. Moreover, the anabolic resistance underlying sarcopenia hampers the exercise-induced response on muscle mass and the level of evidence for this outcome remains poor-to-moderate. Thus, FGF-19 could be considered as a new regulator of skeletal muscle in elderly living with sarcopenia/frailty but there are, to date, only few data available in the literature. First and foremost, it is crucial to understand the relationship between postprandial FGF-19 and muscle which has not been characterized yet. Preliminary data suggest an inverse relationship between FGF-19 and physical function (OR= 0.33 \[0.15;0.7\] for the highest tertile of FGF-19) that persisted only in the cluster of frail individuals (OR= 0.19 \[0.05;0.65\]. Mechanistically, this suggests a positive feedback loop of the bile acids-gut-microbiota-FGF-19 in the presence of frailty/sarcopenia hence indicating that FGF-19 may be a novel biomarker of this condition.

Inclusion Criteria: * Age ≥70 years * Give his/her informed consent * For the FRAIL group: SPPB ≤8, confirmed frailty (≥ 3 criteria in the Fried's appendix of frailty) and a at least a probable sarcopenia (regarding the revised European Working Group of Sarcopenia in Older People cut-offs ie. Low muscle strength either in the handgrip \8, no frailty (no criterion in the Fried's appendix of frailty) and no sarcopenia (normal muscle strength regarding the European Working Group of Sarcopenia in Older People cut-offs). Exclusion Criteria: * Individuals who have undergone cholecystectomy, colectomy, or small bowel resection * Individuals with diabetes undergoing oral treatment with metformin * Body mass index \>35 kg/m2 * Persons admitted to a health or social care facility for purposes other than research * Persons not affiliated with a social security system or beneficiaries of a similar system * Failure to comply with the exclusion period from another study specified in the national volunteer registry * Adults subject to legal protection measures (guardianship, curatorship) * Persons deprived of their liberty by judicial or administrative decision * Persons who have exceeded the annual compensation amount for participation in research protocols * Persons with a chronic progressive or advanced disease detectable by clinical examination and laboratory tests that may interfere with the study's evaluation criteria, the judgment of which is left to the discretion of the research team * Persons with hemiplegia or another form of partial/total paralysis * Contraindications to metabolic testing: severe coagulation disorder, anemia, difficult and painful venous access in the investigator's judgment * Chronic constipation or diarrhea * Taking antibiotics within 15 days prior to the investigations and in the absence of induced digestive disorders (for so-called common antibiotics of the beta-lactam family) or within the month prior to the investigations, at the investigator's discretion (for Augmentin). * Polypharmacy, including drugs known to affect the microbiota and intestinal transit