re: microbiome + therapeutics, I like this finding: https://www.science.org/doi/10.1126/science.aau6323. Thinking about microbiome effects on drug metabolism for already understood drugs seems more actionable to me, at least in the short term.
It's definitely a cool idea, agree on it being more actionable! I was looking into prodrugs a lot recently, and there are also a few examples there of prodrug -> active drug activation via microbiome interactions (https://pubmed.ncbi.nlm.nih.gov/6147110/)
Regarding the cancer microbiome controversy, I am on the side of the skeptics. The issue of mis-identifying human sequences as bacterial (due to human DNA contamination in bacterial reference genomes) is a big problem, and the authors of the original study didn't properly filter out human-derived sequencing reads. That error, by itself, invalidates the paper.
Also, I don't love the conflation of using fecal microbiota transplant (FMT) for gastrointestinal issues and curing anxiety or depression. If FMT stops you from having diarrhea while commuting, you'll definitely experience lower anxiety, but that doesn't mean the FMT affected your anxiety through the gut-brain axis. That's an issue with both studies you linked to.
Nice post - learned a lot.
re: microbiome + therapeutics, I like this finding: https://www.science.org/doi/10.1126/science.aau6323. Thinking about microbiome effects on drug metabolism for already understood drugs seems more actionable to me, at least in the short term.
It's definitely a cool idea, agree on it being more actionable! I was looking into prodrugs a lot recently, and there are also a few examples there of prodrug -> active drug activation via microbiome interactions (https://pubmed.ncbi.nlm.nih.gov/6147110/)
Regarding the cancer microbiome controversy, I am on the side of the skeptics. The issue of mis-identifying human sequences as bacterial (due to human DNA contamination in bacterial reference genomes) is a big problem, and the authors of the original study didn't properly filter out human-derived sequencing reads. That error, by itself, invalidates the paper.
Haven't gotten the chance to do a full read through yet, but liking it so far!
One thing that I think is important, though, is to specify that most of your generalizations about the microbiome are about the human gut microbiome, with the exception of your aside about the tumor microbiome. Other microbiomes (oral, vaginal, skin) and other species have their own issues. Wrote a bit about the vaginal microbiome myself (https://trevorklee.substack.com/p/bacterial-vaginosis-we-contain-multitudes) as well as ground squirrel microbiomes (https://trevorklee.substack.com/p/ground-squirrel-microbiomes-are-neat).
Also, I don't love the conflation of using fecal microbiota transplant (FMT) for gastrointestinal issues and curing anxiety or depression. If FMT stops you from having diarrhea while commuting, you'll definitely experience lower anxiety, but that doesn't mean the FMT affected your anxiety through the gut-brain axis. That's an issue with both studies you linked to.