Fig. 3: PYY–vagal circuits transduce colonic flagellin.

a, Left, vagal responses to intracolonic perfusion of PBS or 2 μg ml⁻¹ flagellin in wild-type mice (n = 7 mice). Right, quantification of peak response to flagellin (n = 7 mice; *P < 0.05 by two-tailed paired t-test). b, Left, vagal responses to intracolonic perfusion of PBS and 2 μg ml⁻¹ flagellin with simultaneous 473-nm-LED or 532-nm-LED stimulation in Pyy^cre;Halo mice (n = 4 mice). Right, quantification of the peak vagal response to flagellin (n = 4 mice; *P < 0.05 by two-tailed Wilcoxon signed ranked test with non-parametric comparisons using the Wilcoxon method). c, Vagal responses to intracolonic perfusion of flagellin in Pyy^cre;Tlr5^fl/fl mice (n = 5 mice) and Tlr5^fl/fl littermate controls (n = 3 mice; for quantification, see Extended Data Fig. 8). d, Fluorescence in situ hybridization of PYY receptor Y2R (encoded by Npy2r) in a subpopulation of neurons in the vagal nodose ganglion. Representative of n = 4 ganglia. Scale bars, 10 μm. e, Left, vagal responses to intracolonic perfusion of PBS or 2 μg ml⁻¹ flagellin before and after intraperitoneal delivery of the Y2R inhibitor (Y2Ri) BIIE-0246 (1 μM; n = 4 mice). Right, quantification of the peak vagal response to flagellin with and without the addition of Y2R inhibitor 1 μM BIIE-0246 (n = 4 mice; *P < 0.05 by Kruskal–Wallis test with non-parametric comparisons using the Wilcoxon method). f, In vivo calcium imaging of vagal nodose neurons positive for Npy2r in response to colonic perfusion of flagellin (2 µg ml⁻¹; n = 4 mice, n = 144 neurons). A total of 43.37% of NPY2R⁺ cells respond to 2 µg ml⁻¹ flagellin. g, Left, in vivo calcium imaging of vagal nodose neurons in response to colonic perfusion of either intralipid (7%) or flagellin (2 µg ml⁻¹). n = 520 neurons, n = 4 mice. Right, number of responding neurons to each stimulus (n = 4 mice, n = 520 neurons). Grey dashed lines in the heat maps represent start and end of perfusion. Error bars and shading represent s.e.m. Graphics in f adapted with permission from ref. ³, AAAS.