P319 - EFFECT OF ORAL GLUTAMINE SUPPLEMENTATION ON INTESTINAL BARRIER STRENGTHENING IN ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) IN MICE

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P319

EFFECT OF ORAL GLUTAMINE SUPPLEMENTATION ON INTESTINAL BARRIER STRENGTHENING IN ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) IN MICE

F. Vandamme1,2, N. Benzekri1, S. Plet2, D. SEGUY1,2,*

1CHU de Lille, 2INFINITE U1286 Inserm, Lille, France

 

Rationale: Acute graft-versus-host disease (GvHD) is the leading cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) following myeloablative conditioning (MAC). Intestinal epithelial damage and intestinal bacterial translocation following MAC and the resulting reduced food intake play a key role in the onset of GvHD. Conversely, early enteral nutrition after transplantation can reduce the frequency and severity of GvHD. This study aimed to assess whether oral glutamine supplementation reduces GvHD severity in mice

Methods: Adult female B6D2F1 mice received drinking water with 1% Gln or water alone (H2O) from d-7. After total body irradiation on d-1 (2×450 cGy), either an allogeneic (A) or a syngenic transplant (S) (2x10⁶ T cells and 5x10⁶ HSC) was performed on d0. On d7, clinical score (CS, 0-10 for symptom severity), ileal histology (villus height (VH), crypt depth (CD), crypt apoptosis (CA, nCrypt+/nCrypt)), expression of claudin (Clau) 3 and 7, and bacterial translocation (BT) in liver cultures were assessed (median [Q1-Q3], Mann-Whitney and Chi square tests)

Results: Three groups (A-Gln, A-H2O, S-H2O, n=18) were analyzed. CS improved in A-Gln (2[1;3]) vs. A-H2O (4[1;10], p=0,005) and vs. S-H2O (2[1;7], p=0,007). VH (µm) was higher in A-Gln (210[183-238]) vs. A-H2O (178[138-227], p<0.0001), while CD (µm) was deeper in A-Gln (133[111-153]) and A-H2O (142[118-171]) vs. S-H2O (99[90-113], p<0.0004). CA (%) in A-Gln (1,7[0,4-4,3]) was less than in A-H2O (4,7[2,6-12,2], p<0.0001) and comparable to that in S-H2O (1,3[0,4-5,1]). Clau 3 and 7 were more expressed in A-Gln than in A-H2O (p<0.048), but not different from S-H2O. There was a trend to a lower BT(%) in A-Gln (44) compared to A-H2O (78, p=0.086)

Conclusion: Oral glutamine supplementation attenuates GvHD by preserving intestinal integrity and limiting crypt apoptosis in mice

Disclosure of Interest: None declared