Fig. 4.
Gut microbiome is essential for morphine-induced chronic systemic inflammation. (A and B) IL-6 expression in morphine-treated GF and ABX mice was reduced compared with WT controls; nGF = 3; nSPF = 10 to 17. (C and D) Morphine effect on IL-6 expression was restored after gut microbiota was reconstituted in GF mice; nGF = 3. (A–D) Data were analyzed using one-way ANOVA followed by Bonferroni’s multiple comparisons test. (E and F) GF and ABX mice were gavaged with microbiota from either saline or morphine-tolerant mice; nGF = 3; nSPF/ABX = 13 to 15. Significance was tested by two-tailed Student’s t test. (G and H) IL-6 expression was detected in WT, TLR2KO, and TLR4KO mice; n = 8 to 16. (I and J) WT and IL-6KO mice were treated with escalating morphine dosing for 8 d; n = 13 to 17. Ftail flick (3, 56) = 206.1. Fhot plate (3, 56) = 268.9. Data were analyzed by one-way ANOVA followed by Bonferroni’s multiple comparisons test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Mean ± SD.