Oh, what a shocking revelation we have here! It turns out that the sneaky little molecule tryptophan, which we’ve all been praising for giving us that blissful post-turkey dinner snooze, might just have a dark side. In the thrilling world of inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), researchers have been playing detective with tryptophan metabolism. And guess what? They’ve found a suspect in the lineup: indole.

Using the ever-so-willing mice in the collagen-induced arthritis (CIA) model, our intrepid scientists discovered that these rodents needed both gut bacteria and a hearty diet of tryptophan to develop arthritis. But wait, there’s more! Just by sprinkling a little indole seasoning on their low-tryptophan diet, voilà, the mice developed arthritis as if by magic. It’s like indole was the secret ingredient in the inflammatory stew, causing all sorts of chaos like increased nasty cytokines (IL-6, TNF, and IL-1β), an army of RORγt+CD4+ T cells, and a cocktail of anti-collagen antibodies ready to party with the complement system.

And because we can’t leave well enough alone, blocking IL-23 in these mice made their arthritis throw a temper tantrum and calm down a bit. But wait, there’s a human angle too! Human colon lymphocytes, when exposed to the indole’s siren call, started singing tunes of IL-17 signaling and plasma cell activation. It’s like indole is the pied piper of inflammation.

So, what’s the grand takeaway from this tale of tryptophan treachery? If we put a stop to the indole concert, we might just find a new way to crash the RA and SpA party. And who knows, maybe one day we’ll all look back and laugh at how a little Thanksgiving molecule could cause such a ruckus in our joints.