FMT Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome (Feb 2024, n=65)

[Riceandbeans32]

https://www.sciencedirect.com/science/article/abs/pii/S1931312824000179

Highlights​

• FMT displays efficacy in ASD children with gastrointestinal comorbidities
• A donor-recipient SGB match suggests a high likelihood of genuine strain transfer
• Donor-recipient intermicrobial interactions are crucial for microbiota transfer
• Associated donor-recipient SGB pairs generally are phylogenetically divergent

Summary​

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.

Here is an argument against the super donor hypothesis. Intuitively this makes sense. When I was pursuing my biology degree we learned about how bacteria, and cells in general, are very sensitive to their environment (i.e. pH, temperature, surrounding ion concentrations, and molecules). It makes sense that getting an FMT from someone with a similar microbial environment to yours (someone who shares a similar diet, is in the same age group, is the same gender, etc.) would lead to better engraftment. Anecdotally, I’ve noticed recipients who do FMTs from people who live with them tend to have good results.

Maybe the answer is somewhere in the middle. There are “super” donors who have a bunch of healthy bacteria that tend to engraft well and have beneficial effects and then there are people who have a similar microbial environment to yours. And maybe the answer is to find a balance of the two — an ideal donor who has the most similar microbial environment to you. This is obviously not easy to do because gut testing is not very useful at its current stage. But maybe trying high quality donors with similar gender, diet, age, etc. until you find the right one, is the way to go.

Given the complexity of the microbiome and the fact that research is still nascent, I think its worth taking into consideration.

 

[Michael Harrop]

Here is an argument against the super donor hypothesis

An argument, yes. But the evidence largely supports donor quality and universal donors -- both the evidence in the wiki https://humanmicrobiome.info/fmt, humanmicrobes.org results, and previous data.

Your linked study is paywalled, but I don't see anything in the available preview text that counters the "super-donor hypothesis".

 

[Riceandbeans32]

“A donor-recipient SGB (species genome bin) match suggests a high likelihood of genuine strain transfer” and “Donor-recipient intermicrobial interactions are crucial for microbiota transfer”.

I’ve read many of those studies but microbiome research is still early in its infancy. It’s also extremely difficult to create high quality microbiome related studies and I've seen many conflicting ones as well. All I am suggesting is that there likely is a component of donor matching that could influence FMT results. My guess would be that a recipient who is not a good match with a super donor might go from a 2/10 to a 6/10 whereas one who is might go from a 2/10 to a 9-10/10.

 

[Michael Harrop]

More strain transfer doesn't necessarily equal better outcomes. "Donor-recipient intermicrobial interactions are crucial for microbiota transfer" is an extremely broad statement, largely under the "no shit" category.

Donor-recipient matching certainly bears some level of importance, but it and this study do not "provide evidence against the super donor hypothesis".

Donor matching, and other customization/individualization, should mostly only come into play once we've first met the requirements/standards for a high-quality donor

All I am suggesting is that there likely is a component of donor matching that could influence FMT results.

Of course! But you opened with "Here is an argument against the super donor hypothesis".

My guess would be that a recipient who is not a good match with a super donor might go from a 2/10 to a 6/10 whereas one who is might go from a 2/10 to a 9-10/10

I'm eager to find out!