A widely distributed gene cluster compensates for uricase loss in hominids (Aug 2023, mice + retrospective analysis of human data, n=30 to n=6573) Causation

[SFBayFMT5]

Since my last post on the oral transplants where I was saying things were starting to fluctuate, I started getting kidney pain and felt as though I were beginning to pass a stone. I knew I had some asymptomatic ones in there for years but none had ever gotten stuck and caused acute pain until recently. A urine test revealed abundant uric acid crystals. Together with a history of systemic symptoms being aggravated after meals where I ate large amounts of meat, I definitely have some sort of uric acid/purine problem.

I recalled a noteworthy paper about the gut microbiome and uric acid from several years back and found it. I assumed it had likely already been posted here, being that long ago, but a search for the word "uric" on this forum only brings up one completely unrelated study about diabetes. So, I'm posting it now...

https://pmc.ncbi.nlm.nih.gov/articles/PMC10421625/

It's long been suspected that the "carnivore" sort of diets many gut sufferers eventually get onto have a dark side, this is a specific piece of evidence for one way in which too much meat/protein intake for those with a disrupted microbiome could cause problems.

There's also another paper from the same year backing a lot of this up: https://www.sciencedirect.com/science/article/pii/S1931312823002044

Abstract​

Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

Click to shrink...