scholarly journals Transplanting a Microbial Organ: the Good, the Bad, and the Unknown

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Dionysios A. Antonopoulos ◽  
Eugene B. Chang

ABSTRACT Fecal microbiota transplantation (FMT) has received increased attention as a therapy for correcting intestinal dysbiosis and restoring a state of health in patients suffering from either recalcitrant infection by Clostridium difficile or more complex disease states, such as inflammatory bowel disease (IBD). The “gut microbial organ” from the donor that is used in these transplants may serve to transfer genetic material between donor and recipient via virus-like particles, specifically bacteriophages, that infect the bacterial component of the microbiota. The recently published study by Chehoud et al. provides evidence for not only the transfer of bacteriophages during FMT but also the transfer of multiple populations of bacteriophages to recipients from the donor microbiota used (C. Chehoud et al., mBio 7:e00322-16, 2016, http://dx.doi.org/10.1128/mBio.00322-16 ). While the clinical significance of these findings remains unclear, nothing short of a diligent and persistent effort is needed to define the intended and unintended consequences of FMT.

2019 ◽  
Author(s):  
Nathaniel D. Chu ◽  
Jessica W. Crothers ◽  
Le T.T. Nguyen ◽  
Sean M. Kearney ◽  
Mark B. Smith ◽  
...  

AbstractFor fecal microbiota transplantation (FMT) to be successful in complex immune diseases like inflammatory bowel disease (IBD), it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize the recipient and persist in sufficient quantity and for a long enough period of time to result in a clinical benefit. But few studies have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial and immune functions. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered a range of competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening clinical symptoms. We similarly evaluated transfer of microbial functions, including desired ones like butyrate production and unintended ones like antibiotic resistance. By profiling bacteria coated with IgA, we identified IgA-coated bacteria associated with inflammation, and we found that microbial interactions with the host immune system can be transferred across people. This transfer of immune function is likely critical for gut microbiome therapeutics for immune-related diseases. Our findings elucidate the colonization dynamics of gut microbes as well as their functions in the context of FMT to treat a complex disease—information that may provide a critical foundation for the development of more-targeted therapeutics.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 997 ◽  
Author(s):  
Derek M. Lin ◽  
Henry C. Lin

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor’s gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.


mBio ◽  
2021 ◽  
Author(s):  
Nathaniel D. Chu ◽  
Jessica W. Crothers ◽  
Le T. T. Nguyen ◽  
Sean M. Kearney ◽  
Mark B. Smith ◽  
...  

Fecal microbiota transplantation (FMT)—transferring fecal microbes from a healthy donor to a sick patient—has shown promise for gut diseases such as inflammatory bowel disease. However, unlike pharmaceuticals, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Raseen Tariq ◽  
Tausif Syed ◽  
Devvrat Yadav ◽  
Larry J. Prokop ◽  
Siddharth Singh ◽  
...  

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