Think of your gut as a lively party, bustling with millions of tiny guests – your gut microbes. It turns out these little partygoers have a surprising influence over the bouncer of your gut party, the intestinal barrier. You see, gut microbes are like party pranksters, and they have a sneaky trick up their sleeves. They know how to tinker with the bouncer’s communication system, a protein called neuropilin-1 (NRP1) and a process named the Hedgehog (Hh) pathway. When the party’s in full swing, these tiny pranksters dial down the bouncer’s walkie-talkie (NRP1 and Hh pathway) through another protein, the Toll-like receptor (TLR)-2. This makes the bouncer a bit lax, weakening our gut barrier. But in a party-free zone (like in germ-free mice), the bouncer’s walkie-talkie is loud and clear, keeping the gut barrier super tight. Future adventures in gut research are set to reveal more about these microbial party-crashers and their pranks. So, stay tuned for more surprising stories from your gut’s party central!

https://doi.org/10.1038/s42255-023-00828-5