Development of a high-throughput approach for testing optimal fecal microbiota transplant material
Abstract
Historically used to treat Clostridioides difficile infection, fecal microbiota transplants (FMT) are now being tested to treat gut and systemic diseases, including (but not limited to) autoimmune, liver, and cardiovascular. Successful FMT relies on components within the donor sample, which may have specific conserved properties that vary greatly between individuals. Screening donors for potentially transmittable conditions is a well-established practice, however, screening material for the likeliness of a successful clinical outcome or finding the best match of material for patients has not been undertaken. We hypothesized an optimal donor may be selected by high-throughput in vitro screening of fecal microbiota. The objective was to (1) develop a high-throughput in vitro approach to assess the microbiome of a FMT population; and (2) to utilize a test population to demonstrate the developed approach using five protected FMT donors and five atherosclerosis patients. 16S rRNA gene microbiota sequencing was undertaken on samples before and after treatment with toxic compounds [trimethylamine, p-cresol] or their precursors. An intestinal barrier integrity model assessed how toxin components impacted permeability. The modelling represents a reproducible, straightforward approach for assessing a large sample population given treatment under controlled conditions. This is important because pinpointing successful attributes is difficult, given the influence of lengthy experimental times, small sample volume or the influence of confounding factors. Considering donors individually, results revealed specific characteristics towards less trimethylamine-producing capabilities and potential barrier-promoting qualities in two of the protected donors. This high-throughput approach may be useful to optimize the efficacy of future FMT therapy.