A new study published in the Clinical Infectious Diseases analyzed the detrimental effect of broad-spectrum antibiotics on intestinal microbiome diversity in patients after allogeneic stem cell transplantation (ASCT) since loss of gastrointestinal (GI) diversity correlates to acute GI Graft-versus-Host Disease (GvHD). This was a retrospective analysis including 161 ASCT patients, wherein serial examination results of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters were utilized within the first 10 days after ASCT, in order to identify potential commensal microbiota sparing antibiotics. Patients were divided into 3 subgroups based on antibiotic activity - rifaximin without systemic antibiotics, rifaximin with systemic antibiotics, and ciprofloxacin/metronidazole with/without systemic antibiotics). The results indicated that mono-antibiosis with rifaximin revealed higher 3-IS levels, higher Clostridium Cluster XIVa (CCXIVa) abundance and higher Shannon index compared to ciprofloxacin/metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to ciprofloxacin/metronidazole with/without systemic antibiotics as these patients showed still higher 3-IS levels, higher CCXIVa copy numbers, and higher Shannon index. Even for this larger cohort of patients, outcome was superior with regard to GI-GvHD and lower transplant related mortality in those receiving rifaximin plus systemic antibiotics compared to patients on other types of systemic antibiotic treatment. Antibiosis with ciprofloxacin/metronidazole, piperacillin/tazobactam, meropenem/vancomycin, ceftazidime or multiple systemic antibiotics showed significantly lower 3-IS levels compared to mono-antibiosis with rifaximin or intravenous vancomycin. From the findings, it was inferred that the use of different types of antibiotic treatment shows different impact on markers of microbiome diversity. Rifaximin facilitates a higher intestinal microbiome diversity even in the presence of systemic broad-spectrum antibiotics.