Thanks, Ruairi!

Would be great to be added, thanks

@gregmedlock.bsky.social and me for the drug development side

Totally 🙃 thanks for commenting!

Interesting… so that would be acting in the opposite direction (with respect to succinate concentrations) to e.g. doi.org/10.1016/j.celrep.2021.109521

Hmmm… We show that both Phascolarctobacterium and Dialister consume succinate, but that (1) Dialister is slower and that (2) IBD patients are more likely to have Dialister compared to Phasco. How do you think that might influence mucosal healing?

Thanks, Karna!

In summary: Succinotypes stratify human gut microbiomes based on rate of succinate consumption, setting a mechanistic basis for a functional microbiome biomarker and therapeutic target. pharmabiome.com doi.org/10.1101/2023...

Indeed, we looked at the association of succinotypes with different diseases and found that IBD patients are significantly more likely to have a D-succinotype compared to a P-type.

Finally, because succinate accumulation is implicated in disease—in particular IBD (e.g. doi.org/10.1007/s111... ) we hypothesized that this difference in consumption rate might provide a mechanistic link between microbiome function and disease pathophysiology.

Going back to the consumption rate differences, we expected D succinotype microbiomes to consume succinate more slowly than P succinotypes, and amazingly D-types had higher fecal succinate concentrations than P-types!

Because of this mutual exclusivity, we decided classify human gut microbiomes into either D- or P-succinotypes, which to our understanding is a rare example of a classification based on function rather than just statistical patterns.

If this grouping were relevant, we expected Phascolarctobacterium and Dialister to be anticorrelated across human gut microbiomes. This turned out to be clearly the case, with the two genera mutually exclusive in the vast majority of any fecal samples we could get our hands on.

We thus supposed that Phascolarctobacterium and Dialister would be the relevant succinate consumers in actual gut environments (where alternative nutrient sources should be plentiful), forming a two-taxon functional group.

Interestingly, while Phascolarctobacterium and Dialister directly consumed the supplied succinate, Flavonifractor had diauxic consumption, suggesting it had a preference for any other nutrients in the base medium over succinate.

We thus hypothesized that these three bacteria are the relevant succinate consumers, and that differences in their individual consumption rates resulted in differences in the whole-community consumption rates, which turned out to be the case!

We discovered these using our NicheMap approach doi.org/10.1101/2023..., where we observed that fecal microbiomes differ in terms of the rate at which they consumed succinate, and this rate correlated with three different bacterial genera: Phascolarctobacterium, Dialister, and Flavonifractor.

So sock-dogs per second? Sounds like a measure of knitting speed. Totally understandable, very easy to confuse knitting with space travel.