Phage Therapy of Extensively Drug Resistant Acinetobacter baumannii Infections: Evaluating the Distribution of Phage in Human Body and the Impact on Gut Microbiome

Abstract

Abstract Background Numerous studies have reported the successful cases of bacteriophage therapy in infections caused by multidrug-resistant Acinetobacter baumannii (MDRAB). However, the safety of phage therapy, as well as bacteriophage resistance, and the impact on human gut microbiome remains challenging. Methods The genomic DNA of phages and pathogen were detected by real-time PCR from 14 blood samples, 13 sputum samples and 10 fecal samples, respectively. The default value of negative result was set as 45 of Ct. The composition of gut microbiota was analyzed by Illumina-based 16S rRNA sequencing from fecal sample. Results Negative PCR results were observed for A. baumannii and the bacteriophage DNA in most blood samples. In the sputum samples, the CT values of phages showed a decreasing trend (45 to 14.7) and that of A. baumannii slowly increased (13.8 to 45) in the first phage therapy phase. During the second phase, the CT values of phage maintained at 28.5 to 26.8, and the CT values of the pathogen kept in a relatively lower level (13.2–18.1). In the fecal samples, we observed the significant decrease in the CT value of phage post two phases of bacteriophage treatment (35.5 to 22.5 and 32.6 to 22.7). Sequencing analysis demonstrated a largely changed microbiota profile both at the phyla and genus level during phage therapy. Conclusion Inhaled phages appears to be present in human blood, accumulate in the intestines and modify the community of gut microbiome.