Impact of transforming growth factor-β2 enriched food for special medical purposes on nutritional status, microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation: prospective analysis of 192 consecutive patients

Background and aims: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an essential treatment for various diseases despite being burdened by severe malnutrition, serious infections, graft-versus-host disease (GVHD) and gut microbiota dysbiosis. There is growing evidence suggesting that nutritional interventions may potentially lower these risks. In particular, nutritional supports enriched with the TGF-β2 have shown promising benefits in Crohn's disease thanks to its immunomodulating and anti-inflammatory properties. Given the pathophysiological and clinical similarities between IBDs (Inflammatory Bowel Diseases) and gastrointestinal acute GVHD (GI aGVHD), this prospective study investigated the impact of a TGF-β2 enriched Food for Special Medical Purposes (TGF-β2 FSMP) on nutritional status, transplant outcomes, and microbiota composition in patients undergoing allo-HSCT. Methods: Patients were divided into two groups according to their TGF-β2 FSMP consumption defined by study protocol: Group A (Treatment Ratio ≥50 %, more than 50 % of prescribed FSMP assumed) and Group B (Treatment Ratio <50 %). Transplant outcomes (Overall Survival, Transplant Related Mortality, Cumulative Incidence of acute GVHD, infectious complications, lymphocytes count 28 days after transplantation and microbiota composition) were analyzed according to TGF-β2 FSMP consumption. Results: A total of 192 consecutive patients who have undergone allo-HSCT were included, 112 in group A and 80 in group B. Adequate TGF-β2 FSMP intake (Group A) significantly reduced severe malnutrition (PG-SGA C) at day +28 post-transplant, improved overall survival (OS) (median 42.2 months in Group A vs. 29.2 months in Group B, p = 0.014), and decreased non-relapse mortality (NRM) (p = 0.018). Furthermore, Group A exhibited a lower incidence of clinically significant acute graft-versus-host disease (aGVHD) (MAGIC II-IV) (18.4 % in Group A vs. 45.4 % in Group B, p < 0.001), particularly gastrointestinal aGVHD (12.8 % in Group A vs. 42.3 % in Group B, p < 0.001), and a reduced incidence of pneumonia (24.1 % in Group A, vs. 48.1 % in Group B, p < 0.001). Moreover, Group A showed significantly higher counts of NK lymphocytes (CD56+ and CD16+) at day +28 (p = 0.012 and p = 0.002, respectively). Microbiota analysis on 32 representative patients revealed no significant differences between groups after TGF-β2 FSMP supplementation, while Firmicutes/Bacteroidetes (phyla commonly dominating gut microbiota) ratio showed a significant decrease in Group A at day +28 post-transplant compared to baseline (p = 0.011). Multivariable analysis identified adequate TGF-β2 FSMP intake, absence of disease relapse, and lymphocyte count ≥140 cells/μL at day +28 as independent predictors of improved OS. Conclusions: These findings highlight the potential of TGF-β2 FSMP as a crucial nutritional intervention in allo-HSCT, positively influencing nutritional status, immune reconstitution, microbiota composition, and overall transplant outcomes. Further randomized trials are needed to confirm these data.