Long-term impact of fecal transplantation in healthy volunteers

Abstract

BackgroundFecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes.ResultsWe have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost ∼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome.ConclusionsThe FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.

Gut microbiota alterations due to fecal transplant

“…It has been important to establish the fact of donor microorganisms colonization of the recipient's intestine [Li et al, 2016;Lee et al, 2017;Kumar et al, 2017;Smillie et al, 2018]. Moreover, colonization of the healthy volunteers intestines by healthy stool microorganisms of healthy donor has been shown [Goloshchapov et al, 2019]. However, only the behavior of donor strains has been demonstrated.…”

“…Using the RECAST sorting approach the shotgun metagenomic data from three FMT studies including healthy volunteers [Goloshchapov et al, 2019], patients with clostridial colitis [Lee et al, 2017] and metabolic syndrome [Vrieze et al, 2012] were analyzed. According to taxonomic profiling, the settle and stay "baskets" are similar and differ from not settle and gone categories respectively.…”

“…An additional criterion for data selection was the presence of aligned sampling points between recipients. The data from FMT-allogeneic experiments in healthy volunteers [Goloshchapov et al, 2019] (healthy FMT), patients with Clostridioides difficile infection [Lee et al, 2017] (CDI) and metabolic syndrome [Vrieze et al, 2012] (MS allogeneic) were used. Additionally, autologous FMT data were used on patients with metabolic syndrome [Vrieze et al, 2012] (MS autologous) and from healthy people without interventions [Voigt et al, 2015] (Control) as comparison groups.…”

“…It is worth noting that the V1 volunteer (healthy FMT dataset) received two FMTs from one donor. The second FMT was carried out 38 days after 100the first FMT [Goloshchapov et al, 2019]. In total, 249 metagenomic stool samples were used in the study.…”

“…A number of studies are ongoing in inflammatory bowel diseases (IBD) (Crohn's disease, nonspecific ulcerative colitis) and metabolic disorders. The changes of the intestinal microbiota during FMT by colonization with donor bacteria are described in the case of IBD [Li et al, 2016;Kumar et al, 2017;Lee et al, 2017;Smillie et al, 2018] and healthy volunteers [Goloshchapov et al, 2019]. However, neither the therapeutic mechanism of the FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been described.…”