Fecal microbiota transplantation reduces resistant bacteria colonization in kidney transplant recipients

Bacterial infections are a greater threat as they are most common causes of morbidity and mortality worldwide. Multi-drug resistant organisms (MDROs) represent an ever-increasing share of causative agents of infection, and their prevalence is now just as high. Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance.

Very few studies report about efficacy of fecal microbiota transplantation (FMT), and reduction in MDRO colonization, where not much is known about its mechanisms. A new trial published in Science Translational Medicine reports that FMT may provide a path to exploit strain competition to reduce MDRO colonization. It is known kidney transplant patients are at high risk for MDRO colonization and infection, as they receive prophylactic antibiotics after transplant, which can select for MDROs. They are thus a priority for decolonization, because many of the antibiotics used to treat MDRO infections are nephrotoxic.

The researchers conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). A total of 11 participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT.

The key findings of the study are

• Key taxa of microbes (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor was used in the study.

• They engrafted the above combination of feces in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development.

• Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset.

• Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase–producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT.

• These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.

Researchers concluded that FMT resulted in faster MDRO decolonization and protected study participants from recurrent infection. In some participants, extended spectrum β-lactamase (ESBL)–producing strains were replaced by non-ESBL strains, suggesting that strain competition rather than eradication may occur after FMT.

Further they added these findings support the efficacy of FMT and provide valuable insights into the mechanisms by which FMT may lead to MDRO decolonization.

Reference: MICHAEL H. WOODWORTH , ROTH E. CONRAD, MARINA HALDOPOULOS et al; Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement; SCIENCE TRANSLATIONAL MEDICINE, 1 Nov 2023 Vol 15, Issue 720; DOI: 10.1126/scitranslmed.abo2750.