Previous studies have shown that high microbial diversity, increased butyrate producers, and reduced abundance of Enterococcus are associated with improved overall survival (OS) following allogeneic hematopoietic cell transplantation (allo-HCT).¹ Increased fiber intake has been linked to enhanced microbial growth and the production of short-chain fatty acids (SCFAs) such as butyrate and acetate, which promote gut homeostasis and limit the proliferation of opportunistic pathogens.¹ However, the relationship between dietary fiber intake and acute graft-versus-host disease (aGvHD) outcomes remains underexplored.¹ As such, the dietary patterns of allo-HCT patients were examined, and preclinical studies using a mouse model with controlled dietary fiber concentrations were conducted to investigate the mechanisms by which dietary fiber modulates GvHD outcomes.¹ Findings from the studies were presented by Dr. Jenny Paredes from the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope National Medical Center, California, the United States during the ASH Annual Meeting & Exposition 2024.¹

High-resolution dietary data were collected from 173 allo-HCT patients at Memorial Sloan Kettering Cancer Center, spanning from 7 days prior to transplantation to 30 days post-transplantation (3,837 days).¹ In addition, 16S ribosomal ribonucleic acid (rRNA) sequencing data from fecal samples (1,028 samples) and gas chromatography-mass spectrometry (GC-MS) data on fecal SCFA concentrations were obtained for a sub-cohort of patients with acute lower gastrointestinal (GI)-aGvHD (n=24) and non-GvHD (n=29), matched by stool sample availability.¹ The primary study outcomes were the associations between longitudinal fiber intake and microbial markers, including α-diversity, butyrate producers, and concentrations of fecal SCFAs, comparing patients with lower GI-aGvHD to those without.¹ Longitudinal data analysis was performed using generalized estimating equations to assess these associations.¹ To account for the high variation in patients’ dietary intake trajectories and the interactions between macronutrients, latent trajectory class analysis was employed to identify dietary intake patterns and their correlation with patient survival.

In the preclinical mouse model, C57BL/6J mice were transplanted into BALB/c mice and treated with cellulose at concentrations of 0%, 6%, 12%, and 40%.¹ The study evaluated the effects of dietary fiber on GvHD, including survival, with 180 mice in total (30 per group), and analysis of fecal microbial composition using shotgun sequencing (n=165 samples).¹ The concentrations of SCFAs were measured using GC-MS, with 32 samples analyzed across the groups.¹ Immune composition was assessed through flow cytometry, involving 45 mice (15 per group), while gene expression from the lamina propria cells of mouse colons was analyzed using single-cell sequencing (scSeq), with 9 mice in total (3 per group).¹

In allo-HCT patients, higher fiber intake was associated with increased microbial α- (p=0.007) and β-diversity (p<0.001), and higher butyrate (p<0.001) and acetate (p<0.001) concentrations.¹ Conversely, patients with lower GI-aGvHD exhibited reduced butyrate (p=0.007) and acetate (p=0.008) levels.¹ Latent trajectory class analysis revealed two groups: high fiber (HF) and low fiber (LF) intake, with the HF group showing significantly better OS (plog-rank=0.045) and a lower cumulative incidence of lower GI-aGvHD (p=0.04).¹

In the preclinical model, mice on a fiber-rich diet (12% cellulose) had reduced GvHD lethality (p=0.02).¹ In comparison to 0% cellulose, they also showed a higher regulatory T cell over conventional T cells (Treg/Tconv) ratio (p=0.0089), and increased cecal butyrate concentrations (p=0.0382).¹ Additionally, scSeq analysis revealed increased expression of epithelial homeostasis genes, including Muc13, Claudin-7 (Cldn7), and E-cadherin.¹

In conclusion, higher fiber intake in allo-HCT patients was associated with improved OS, reduced incidence of lower GI-aGvHD, increased microbial α- and β-diversity, and higher fecal SCFA concentrations, particularly butyrate.¹ Similarly, a 12% cellulose diet in a preclinical GvHD model enhanced epithelial homeostasis gene expression, enhanced the Treg/ Tconv ratio, and decreased GvHD lethality.¹ These findings suggest that dietary fiber plays a role in preventing GvHD.¹