PD672 - FECAL MICROBIOTA TRANSPLANTATION FROM PANCREATIC CANCER PATIENTS TRANSFERS DONOR METABOLIC TRAITS TO GERM-FREE MICE

Linked sessions

PD672

FECAL MICROBIOTA TRANSPLANTATION FROM PANCREATIC CANCER PATIENTS TRANSFERS DONOR METABOLIC TRAITS TO GERM-FREE MICE

Y. M. Dupertuis1,*, B. Zidi1, D. Rigo2, V. Lazarevic3, O. Bejuy4,5, A. Hemmer1, M. Trajkovski2, J. Schrenzel3, T. Koessler6, L. Genton1

1Clinical Nutrition, Geneva University Hospitals, 2Department of cell physiology & metabolism, University of Geneva, 3Genomic Research Laboratory, Geneva University Hospitals, 4Department of Radiology and Medical Informatics, University of Geneva, 5CIBM Center for Biomedical Imaging, 6Medical Oncology, Geneva University Hospitals, Geneva, Switzerland

 

Rationale: Pancreatic cancer patients (PC) exhibit metabolic disturbances that rapidly progress to cachexia. This study investigates the contribution of gut microbiota in the cachexia process by assessing the effects of fecal microbiota transplantation (FMT) from PC donors on body weight and metabolic parameters in germ-free mice.

Methods: Fifteen newly diagnosed, treatment-naïve PC were matched to 15 healthy volunteers (HV) for age (66 ± 13 y) and sex (53% men). FFMI was assessed by bioelectrical impedance, appetite by visual analogue scale, and energy coverage by indirect calorimetry (Q-NRG®) and 3-day dietary record. Fasting blood glucose was measured. FMT was performed in 8-week-old germ-free male C57BL/6J mice over a 28-day period (2 mice/donor). Food intake, body weight, insulin tolerance (5-h fast, 2 U/kg IP), and microPET/CT imaging were recorded. Data (medians, IQR) were analyzed using linear mixed-effects models.

Results: Compared with HV, PC showed reduced appetite and energy coverage, causing weight loss over 6 months, without FFMI-defined sarcopenia. Blood glucose was higher in PC and a similar trend was observed in FMT recipient mice. In contrast to PC donors, mice receiving their FMT gained more weight than those receiving HV FMT.

FMT donors

HV

PC

P

Energy need coverage (%)

107 (29)

69 (40)

0.012

Body weight loss (%)

0.0 (1.2)

5.6 (6.1)

<0.001

FFMI (Kg/m2)

19.9 (2.8)

20.0 (3.3)

0.587

Glucose (mmol/L)

5.4 (1.1)

6.7 (2)

0.010

Mice

 

 

 

Daily food intake (g)

3.1 (0.4)

3.2 (0.6)

0.256

Body weight change (%)

6.7 (8.7)

9.4 (9.5)

0.026

Quadri (SUVmax)

0.32 (0.22)

0.37 (0.14)

0.453

Glucose (mmol/L) 

7.1 (1.8)

8.4 (2.9)

0.058

Conclusion: FMT from PC donors tended to confer a diabetic-like phenotype in recipient mice, marked by insulin resistance and increased weight gain, suggesting that the gut microbiota of newly diagnosed patients is not a primary driver of cachexia.

Disclosure of Interest: None declared