Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice

Abstract

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient’s microbiota to that of the donor’s, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

“…However, few experimental and clinical studies have addressed the contribution of antibiotic pre-conditioning before FMT to donor microbiota engraftment efficacy and results are still contradictory. For instance, Freitag et al, have observed that pre-treatment with antibiotics did not improve the engraftment of donor microbiota, but did improve the engraftment of specific bacteria in the context of Clostridium infection [34]. By contrast, Le Roy et al observed that pre-treated groups (with laxatives or antibiotics) harbored a significantly better engraftment and phenotype in context of obesity [27].…”

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis

“…Ongoing debate exists regarding the pre-treatment of recipients with antibiotics prior to FMT to increase efficacy [ 71 , 72 ]. Conceptually, antibiotic pre-treatment helps provides a proverbial ecological clean slate for the engraftment of donor microbes by freeing up otherwise occupied niches.…”

Cultivation and Genomics Prove Long-Term Colonization of Donor’s Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation

“…As rCDI patients usually have aberrant and less abundant gut microbiota, it might provide bifidobacteria with niches not necessarily present in healthy microbiota. Indeed, a recent mouse study demonstrated that antibiotic pre-treatment prior to FMT enhances specifically the colonization of bifidobacteria (Freitag et al, 2019). In this study, all the recipients were rCDI patients who had received multiple antibiotic treatments before FMT, which may have contributed to the observed colonization of bifidobacteria.…”