scholarly journals Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients

2017 ◽  
Author(s):  
Eli L. Moss ◽  
Shannon B. Falconer ◽  
Ekaterina Tkachenko ◽  
Mingjie Wang ◽  
Hannah Systrom ◽  
...  

AbstractImmunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0182585 ◽  
Author(s):  
Eli L. Moss ◽  
Shannon B. Falconer ◽  
Ekaterina Tkachenko ◽  
Mingjie Wang ◽  
Hannah Systrom ◽  
...  

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S385-S385
Author(s):  
Natasha Kwendakwema ◽  
M Kyle Jensen ◽  
Andrew Pavia ◽  
Elizabeth Doby Knackstedt

Abstract Background CDI is a common cause of bacterial diarrhea, especially in immunocompromised patients. Fecal Microbiota Transplanation (FMT) has been shown to be an effective treatment for recurrent and refractory CDI. The outcomes of FMT treatment for recurrent CDI have been well described in adult populations; however, the data for immunocompromised (IC) patients especially among children are limited. We describe the experience of FMT for treatment of CDI in immuncompromised pediatric patients. Methods We collected clinical data for IC patients <21 years in our pediatric institution who had received FMT for recurrent, refractory, and/or severe CDI. IC patients included those with: solid organ transplantation (SOT) receiving immunosuppressive medications; neoplasm; hematopoietic stem cell transplantation (HSCT); inflammatory bowel disease (IBD) requiring immunosuppressive medication(s). We collected demographic and clinical data, as well as outcomes, including: resolution of diarrhea, CDI relapse, and adverse events within 3 months post-FMT. Results We performed 37 pediatric FMT for recurrent, refractory, and/or severe CDI between September 2012 and February 2017. Of these, 12 were immunocompromised children: 2 with SOT; 3 with neoplasm and/or HSCT; and 7 with IBD on immunosuppressive medication(s). Median age was 11.9 years old (range 3–16 years). 6 (50%) experienced resolution of diarrhea within 1 week post-FMT, and 9 (67%) were C. difficile negative within 3 months of FMT (3 patients did not have follow-up testing). None had CDI relapse within 3 months post-FMT. 3 (25%) had adverse event(s) within 3 months post-FMT, 2 of whom had SAEs: 1 had graft rejection at 2 months post-FMT which ultimately required re-transplantion and 1 had aspiration pneumonitis immediately following FMT. 4 (50%) of the IBD patients had disease remission (clinical, biologic, and/or histologic) in the 3 months post-FMT. Conclusion FMT appears to be effective and reasonably safe for recurrent CDI in immunocompromised pediatric patients. However, the small numbers limit conclusions, especially about safety. Larger multicenter studies are needed to precisely determine safety and efficacy in this specialized population. Disclosures All authors: No reported disclosures.


2014 ◽  
Vol 146 (5) ◽  
pp. S-838 ◽  
Author(s):  
Michael J. Sadowsky ◽  
Alexa Weingarden ◽  
Alexander Khoruts ◽  
Antonio Gonzalez ◽  
Yoshiki Vázquez-Baeza ◽  
...  

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Zhigang Liu ◽  
Isabelle Coales ◽  
Nicholas Penney ◽  
Julie A. K. McDonald ◽  
Jutarop Phetcharaburanin ◽  
...  

ABSTRACT Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria. The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome—increased Enterobacteriaceae—was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery. IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable. It is unclear how well these bacteria colonize in an anatomically normal gut. This is a fundamental question in both defining the function of the RYGB microbiota and evaluating its potential as a nonsurgical treatment for obesity. We monitored the dynamic colonization of the RYGB bacterial consortium and observed that while approximately one-third of the bacterial taxa from the RYGB donor colonized in the gut of the nonoperated recipients, Gammaproteobacteria were unable to colonize for longer than 3 days. The study highlighted that a successful long-term colonization of Gammaproteobacteria-rich RYGB microbiota in nonsurgical animals requires key environmental factors that may be dictated by the intestinal anatomical modification by the surgery itself.


2020 ◽  
Vol 8 (10) ◽  
pp. 1486
Author(s):  
Andrea Quagliariello ◽  
Federica Del Chierico ◽  
Sofia Reddel ◽  
Alessandra Russo ◽  
Andrea Onetti Muda ◽  
...  

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.


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