Impact of Exogenous Lactiplantibacillus plantarum on the Gut Microbiome of Hematopoietic Stem Cell Transplantation Patients Colonized by Multidrug-Resistant Bacteria: An Observational Study

<b>Background:</b><i>Lactiplantibacillus plantarum</i> can inhibit the growth of multidrug-resistant organisms (MDROs) and modulate the gut microbiome. However, data on hematopoietic stem cell transplantation (HSCT) are scarce. <b>Aim:</b> In an observational study, we assessed the impact of <i>L. plantarum</i> on the modulation of the gut microbiome in HSCT patients colonized by MDROs. <b>Methods:</b> Participants were allocated to an intervention group (IG = 22) who received capsules of <i>L. plantarum</i> (5 × 10⁹ CFU) twice per day until the onset of neutropenia or a control group (CG = 20). The V4 region of the 16S bacterial rRNA gene was sequenced in 87 stool samples from a subset of 33 patients (IG = 20 and CG = 13). The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) program was used to predict metagenome functions. <b>Results:</b><i>L. plantarum</i> demonstrated an average 86% (±11%) drug-target engagement at 43 (±29) days of consumption and was deemed safe, well-tolerated, and associated with an increase in the abundance of the Lactobacillales (<i>p</i> < 0.05). A significant increase in <i>Lactococcus</i> and a reduction in <i>Turicibacter</i> (<i>p</i> < 0.05) were identified on the second week of <i>L. plantarum</i> use. Although <i>Enterococcus</i> abundance had a greater rise in the CG (<i>p</i> = 0.07), there were no significant differences concerning the Gram-negative MDROs. No serious adverse effects were reported in the IG. We observed a greater, non-significant pyruvate fermentation to propanoate I (<i>p</i> = 0.193) relative abundance in the IG compared with the CG. <i>L. plantarum</i> use was safe and tolerable by HSCT patients. <b>Conclusions:</b> While <i>L. plantarum</i> is safe and may impact <i>Enterococcus</i> and <i>Turicibacter</i> abundance, it showed no impact on Gram-negative MDRO abundance in HSCT patients.