Preparing the Gut with Antibiotics Enhances Gut Microbiota Reprogramming Efficiency by Promoting Xenomicrobiota Colonization

Abstract

Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.

Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE)

“…Consistent with concept of species competition resulting in reduced FMT success, use of antibiotics prior to FMT may help alter resident gut microbiota in recipients to increase FMT efficacy. This is supported by a meta-analysis of human studies and two studies in mice showing that pretreatment with antibiotics may enhance FMT efficacy 58–60. The inference based on these data is that antibiotics eliminate competition from resident micro-organisms by freeing previously occupied ‘niches’.…”

Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro

“…El-Nachef et al proposed that a combination of bactericidal broad-spectrum antibiotics administered prior to FMT may be necessary to provide the desired outcome (16). Indeed, Ji et al found that a cocktail of ampicillin, neomycin, and vancomycin promoted colonization of allochthonous microbes into specific-pathogen-free mice (42). In this case, the authors concluded that the proposed hypothesis of antibiotics clearing niches to allow such colonization to occur was correct.…”

“…There are two possible reasons for this discrepancy. First, Ji et al utilized healthy mice, in which the resident gut microbial ecosystems are not expected to be representative of the diseased state (42). In contrast, and as an example, UC patients are depleted in microbial diversity, particularly in members of the Lachnospiraceae and Ruminococcaceae families (43).…”

Daily, Oral FMT for Long-Term Maintenance Therapy in Ulcerative Colitis: Results of a Single-Center, Prospective, Randomized Pilot Study.

“…Subjects in both arms of the study were pretreated with antibiotics (cipro oxacin 250mg PO q12 and metronidazole 500mg PO q8 x7 days) for 7 days prior to FMT (or placebo) procedure. This regimen was chosen for its ability to disrupt luminal microbial communities prior to FMT and to promote microbiota reprogramming [22].…”