Impact of Amoxicillin/Clavulanate and Autologous Fecal Microbiota Transplantation (FMT) on the Fecal Microbiome and Resistome

Abstract

Background. Strategies to prevent infections due to multidrug‐resistant organisms (MDROs) are scarce, but it may be possible to limit gastrointestinal MDRO colonization through fecal microbiota transplantation. Our objective was to determine the impact of autologous FMT (auto‐FMT) on the restoration of the gastrointestinal microbiome after antimicrobial exposure. Methods. Ten healthy subjects received 5 days of amoxicillin/clavulanate (amox/clav) 875 mg twice per day. Half were randomized to auto‐FMT by enema and half to saline by enema. Stool was obtained before and after antibiotics, immediately following enema, and at days 7, 30, and 90 post enema. Shotgun metagenomic sequencing facilitated species composition analysis and resistance gene annotation. Species were identified using MetaPhLan and Beta Lactam resistance genes were identified using ShortBRED and the Lahey database. Results. Community Diversity. Effects on the gut microbiota composition varied in response to antibiotics (figure 1). Most notably, subject 8 exhibited a bloom of Proteo‐bacteria. Normal composition was restored after auto‐FMT. Additionally, amox/clav increased Bacteroidetes in some subjects (1‐5) but not in subjects that began with high Bacteroidetes levels (6, 7, 10). Bacteroidetes returned to normal levels in both treatment and control groups. Abundance of Beta‐Lactam Resistance Genes. Subjects 7 and 8 exhibited an increase in Beta Lactam resistance gene abundance following amox/clav treatment (figure 2). Concurrently, subject 8 exhibited a bloom in Proteobacteria, but post‐auto‐FMT, subject 8 exhibited a return to pre‐antibiotic conditions (albeit punctuated by fluctuations in Actinobacteria and Bacteroidetes). Conclusion. The most dramatic change in response to amox/clav observed was a Proteobacteria bloom in 1 subject associated with a surge in resistance gene abundance; however, restoration of the microbiome occurred following auto‐FMT. Additionally, amox/clav treatment led to increased Bacteroidetes abundance in some subjects (5/10); this resolved after saline or FMT enema. In other cases, little change in species composition (4/10) or resistance gene content following antibiotic treatment was observed (8/10).