Abstract

Introduction: The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.

Methods: This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.

Results: Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade ≥2 mucositis (80% vs. 33%, p=0.01) and low fiber intake (10.4 g vs. 13.6 g, p=0.04). They also had more carbapenem exposure (93% vs. 47%, p=0.005) and prolonged antibiotics (11 days vs. 8 days, p=0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.

Conclusion: Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.