scholarly journals Long-term impact of fecal transplantation in healthy volunteers

2019 ◽  
Author(s):  
Oleg V Goloshchapov ◽  
Evgenii I Olekhnovich ◽  
Sergey V Sidorenko ◽  
Ivan S Moiseev ◽  
Maxim A Kucher ◽  
...  

AbstractBackgroundFecal microbiota transplantation (FMT) is now approved for the treatment of refractory recurrent clostridial colitis, but a number of studies are ongoing in inflammatory bowel diseases, i.e., Crohn’s disease, nonspecific ulcerative colitis, and in other autoimmune conditions. In most cases, the effects of FMT are evaluated on patients with initially altered microbiota. The aim of the present study was to evaluate effects of FMT on the gut microbiota composition in healthy volunteers and to track long-term changes.ResultsWe have performed a combined analysis of three healthy volunteers before and after FMT with frozen capsules, followed by evaluation of their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene sequencing (16S seq) and shotgun sequencing (or whole-genome sequencing – WGS). The data analysis demonstrated the 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 and systemic inflammatory response in one volunteer.ConclusionsThe FMT procedure leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition, being relatively safe to the recipients without long-term adverse events.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Oleg V. Goloshchapov ◽  
Evgenii I. Olekhnovich ◽  
Sergey V. Sidorenko ◽  
Ivan S. Moiseev ◽  
Maxim A. Kucher ◽  
...  

Abstract Background Fecal 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. Results We 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. Conclusions The 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.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Oryan Agranyoni ◽  
Sapir Meninger-Mordechay ◽  
Atara Uzan ◽  
Oren Ziv ◽  
Mali Salmon-Divon ◽  
...  

AbstractThe link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severine P. Parois ◽  
Susan D. Eicher ◽  
Stephen R. Lindemann ◽  
Jeremy N. Marchant

AbstractThe influence of feed supplements on behavior and memory has been recently studied in livestock. The objectives of the study were to evaluate the effects of a synbiotic on: an episodic-like (SOR: Spontaneous Object Recognition), a working (BARR: Fence barrier task), a long-term (TMAZE: Spatial T-maze task) memory test and on gut microbiota composition. Eighteen female piglets were supplemented from 1 to 28 days of age with a synbiotic (SYN), while 17 served as control (CTL). Feces were collected on days 16, 33 and 41 for 16S rRNA gene composition analyses. In the SOR, SYN piglets interacted more quickly with the novel object than CTL piglets. In the BARR, SYN piglets had shorter distances to finish the test in trial 3. In the TMAZE, SYN piglets were quicker to succeed on specific days and tended to try the new rewarded arm earlier during the reversal stage. Difference of microbiota composition between treatments was nonexistent on D16, a tendency on D33 and significant on D41. The synbiotic supplement may confer memory advantages in different cognitive tasks, regardless of the nature of the reward and the memory request. Difference in memory abilities can potentially be explained by differences in microbiota composition.


mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Leen Boesmans ◽  
Mireia Valles-Colomer ◽  
Jun Wang ◽  
Venessa Eeckhaut ◽  
Gwen Falony ◽  
...  

ABSTRACT Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of next-generation probiotics are the design of formulations with a reasonable shelf life as well as the safety demonstration of an intervention in healthy volunteers. One such potential next-generation butyrate-producing probiotic is Butyricicoccus pullicaecorum 25-3T, with demonstrated safety in in vitro as well as animal models. Here, we examined the strain’s safety, tolerability, and impact on microbiota composition and metabolic activity in healthy volunteers in a randomized, double-blind, placebo-controlled crossover study in 30 healthy volunteers. The study design consisted of two 4-week intervention periods (108 CFU B. pullicaecorum [treatment] or maltodextrin [placebo] per day) with a 3-week washout in between. We assessed adverse events, blood parameters (primary endpoints), and fecal microbiota composition and metabolite profiles (secondary endpoints). The number of reported adverse events during the B. pullicaecorum treatment was similar to that of placebo intervention, as were observed changes in blood chemistry parameters, bowel habits, and fecal calprotectin concentrations. Administration of the strain did not induce any disruptive effect in microbiota composition or metabolic activity. In this first human intervention trial with a butyrate-producing Clostridium cluster IV isolate, we demonstrated B. pullicaecorum 25-3T administration to be both safe and well tolerated by healthy participants. This safety study paves the way for the further development of the strain as a next-generation probiotic. IMPORTANCE This study is the first to determine the safety and tolerance in humans of a butyrate-producing Clostridium cluster IV next-generation probiotic. Advances in gut microbiota research have triggered interest in developing colon butyrate producers as next-generation probiotics. Butyricicoccus pullicaecorum 25-3T is one such potential probiotic, with demonstrated safety in vitro as well as in animal models. Here, we produced an encapsulated B. pullicaecorum formulation that largely preserved its viability over an 8-month storage period at 4°C. Administration of this formulation to healthy volunteers allowed us to establish the intervention as safe and well tolerated. The probiotic intervention did not cause disruptive alterations in the composition or metabolic activity of health-associated microbiota. The results presented pave the way for the exploration of the impact of the strain on microbiota alterations in a clinical setting.


2021 ◽  
Vol 53 ◽  
pp. S367-S368
Author(s):  
N. Lopizzo ◽  
M. Marizzoni ◽  
M. Mazzelli ◽  
V. Begni ◽  
L.M. Borruso ◽  
...  

Author(s):  
Fontana ◽  
Panebianco ◽  
Picchianti-Diamanti ◽  
Laganà ◽  
Cavalieri ◽  
...  

Background and aims: Microbiota heterogeneity among humans is mainly due to genetic background, age, dietary habits, lifestyle and local environments. In this study we investigated whether the gut microbiota profile of Italian healthy volunteers could differ based on their geographical origin. Materials and Methods: 16S rRNA gene sequencing was employed to analyze the gut microbiota of 31 healthy volunteers from three different Italian regions: Apulia (South), Lazio (Center) and Lombardy (North). Results: Differences in microbiota composition were detected when the study participants were grouped by their region of origin and when they were classified based on age classes (p-values < 0.05). Also species richness was significantly different both according to Italian Regions (median richness: 177.8 vs. 140.7 vs. 168.0 in Apulia, Lazio and Lombardy; p < 0.001) and according to age classes (median richness: 140.1 vs. 177.8 vs. 160.0 in subjects < 32, 32–41 and > 41 years; p < 0.001), whereas the Shannon index and beta diversity did not change. Conclusions: This study identified differences in the gut microbiota composition and richness among individuals with the same ethnicity coming from three different Italian regions. Our results underline the importance of studies on population-specific variations in human microbiota composition leading to geographically tailored approaches to microbiota engineering.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.


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