Fig. 4: Leptin signalling is necessary to induce short-term alterations in the gut microbiota.

a, Schematic representing the experimental outline of central leptin treatment under HFD conditions. b, Heatmap representations from the ANCOM-BC analysis at the family level. Data are represented by the effect size (log fold change). Microbial taxa with statistically significant differences between vehicle-treated and leptin-treated groups in mice fed with standard diet (SD) (left heatmap) and mice fed with an HFD (right heatmap) at 2 and 4 h after treatment in specific gut sections are shown (n = 7–10 mice per group). Stars indicate statistically significant differences compared to the control group; q values for the differences depicted in the heatmaps are provided in Supplementary Table 1. c, Volcano plot displaying statistically significant differences in metabolites in the duodenal luminal content between mice centrally treated with vehicle or leptin (red, upregulated; blue, downregulated; black, no changes; n = 6 mice per group). d, Bar plot visualization of significantly changed metabolites (log₂ fold change). e, Schematic representing the experimental outline of the antibiotic and central leptin treatment study. f, Sankey plot of the top 50 overrepresented GO pathways and related biological categories for the leptin versus vehicle groups comparing untreated (water, left) or antibiotic-treated (right) conditions (n = 6–14 mice per group). The GO pathways are ordered according to ascending P value. Details on GO categories and P values are provided in Supplementary Table 2. g,h, Adrenaline (g) and noradrenaline (h) levels in the duodenum of mice fed with standard or HFD 2 h after central leptin treatment. Sample sizes in g: vehicle (n = 6); leptin, vehicle HFD and leptin HFD (n = 8). Sample sizes in h: n = 8 per group. g,h, Data are represented as the mean ± s.e.m. *P = 0.0313, ***P = 0.0006, ****P < 0.0001. Statistical significance was determined using a two-way ANOVA followed by Tukey’s test.

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