Recipient independent high accuracy FMT prediction and optimization in mice and humans

Abstract

Background Some microbiome composition can be associated with negative outcomes, including among others, obesity, disease and the failure to respond to treatment. Microbiota manipulation or supplementation have been argued to restore the microbiome associated with a healthy condition. Fecal Microbiota Transplantation (FMT) is among the most popular microbiome intervention procedures. Current practices are to choose the transplanted microbiome based on the donor phenotype, and not based on the expected recipient phenotype. However, the two differ drastically. We here propose an algorithm to predict the expected outcome of FMT from the donor phenotype, and optimize the FMT for different required outcomes. Results We here show, using multiple microbiome properties, that the donor and recipient phenotypes differ widely, and propose a tool to predict the recipient phenotype after the FMT using only the donors' microbiome and when available demographics for transplants from humans to either antibiotic treated mice, or other humans. We then extend the method to optimize the best-planned transplant (bacterial cocktails) by combining the predictor and a genetic algorithm (GA). We validate the predictor using a de-novo FMT experiment highlighting the possibility to choose transplants that optimize an array of required goals. We further show that a limited number of taxa is enough to produce an optimal FMT. Conclusions Over the shelf FMT require recipient independent optimized FMT selection. Such a transplant can be from an optimal donor, or from a cultured set of microbes. We have here shown the feasibility of both types of donations in antibiotic treated mice and for transplants between humans.

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

“…Such variations can differ across mouse vendor facilities, posing challenges to reproducibility [45][46][47][48] . Additionally, while differences in the GM of the recipient contribute to these discrepancies, their impact might be less pronounced compared to the variability originating from donor materials 49,50 .…”

Current landscape of fecal microbiota transplantation in treating depression

“…Secondly, In the context of treating depression, although FMT is an emerging therapeutic approach, with innovation and progress, is currently challenged by the lack of standardized assessment protocols (115). This lack has resulted in the number of bacterial species detected in recipient fecal samples being drastically dependent on the depth of sequencing technology, highlighting inconsistencies in research methodology and the need for further analytical techniques (116). Although the majority of current studies have focused on analyzing changes in fecal microbial composition before and after FMT, there is a distinct lack of research into the detailed description of pathogens and beneficial bacteria associated with depression and the mechanisms by which they interact.…”

The Role of Microbiota in Animal Physiology: An Integrative Review

“…Presently, the selection of FMT donors focuses on the donor's observable traits rather than the expected microbial composition in the recipient and its potential health advantages. Nonetheless, there is a significant discrepancy between the conditions of the donor and the recipient after the transplant [11].…”

“…In addition, it developed a constitution that wou ld help to pick the most adequate bacterial cocktail for transplantation. Due to this the researchers established the feasibility of optimal FMT selection, which can be performed using an ideal donor or ready-to-use cultured set and are effective on both mice and humans [11].…”