Extended Data Fig. 1: Stress-induced behavioral changes.

a–c, Apparatuses for the SD protocol model (a), the AR model (b) and the light–dark box test (c). d,e, Total entry times in light box (d) and total locomotion (e) of Ctrl (n = 14) and SD (n = 13) preconditioned mice in the light–dark box test. Two-tailed Mann–Whitney test was applied for statistical analysis (P values are shown between indicated groups). A representative result from five independent experiments is shown. f–h, A typical image showing virtual zone division in the open-field test (f). Total entry times (g) and the duration of stay (h) in the central zone were compared between Ctrl (n = 10) and SD (n = 18) mice. Two-tailed Mann–Whitney test was applied for statistical analysis (P values are shown between indicated groups). A representative result from five independent experiments is shown. i, Total duration of grooming activities of Ctrl (n = 12) and SD (n = 11) mice in the splash test. A two-tailed Mann–Whitney test was applied for statistical analysis (P = 0.0012). A representative result from three independent experiments is shown. j–l, A diagram illustrating the apparatus used in the social avoidance test and its procedures (j). Duration of stay in the ‘interaction zone’ (k) and social-interaction ratio (l) in the absence or presence of the ‘target (CD-1)’ mouse were measured in Ctrl (n = 12) and SD (n = 33) mice. A two-tailed Man–Whitney test was applied for statistical analysis (P values are shown between indicated groups). A representative result from four independent experiments is shown. m, The survival of Ctrl and SD mice that received chemotherapy with MTX or PBS in an AOM–DSS-induced colon carcinogenesis model were compared with log-rank test (n = 13 mice for Ctrl, n = 14 mice for SD, n = 12 mice for Ctrl OXA, n = 15 for SD OXA). Results from two independent experiments are combined and shown. n,o, On day 55 after the first injection of AOM, the number (n) and total size (o) of neoplastic nodules in the colon and rectum were calculated in Ctrl (n = 6) and SD (n = 7) groups with a stereo microscope. Two-tailed Mann–Whitney test was applied for statistical analysis ({ values are shown between indicated groups). A representative result of two independent experiments is shown. p–r, The consumption of food (p) (n = 10 mice for Ctrl, n = 17 mice for SD) and water (q) (n = 9 mice for Ctrl, n = 20 mice for SD) and body weight (r) (n = 19 mice for Ctrl, n = 20 mice for SD) were measured in Ctrl and SD mice daily during the 10-d SD procedure. Two-tailed Mann–Whitney test was used for statistical analysis (P values are shown between indicated groups). A representative result of two independent experiments is shown. All dot plots are shown as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ns, not significant.