Figure 5
Morphine-induced intestinal and hepatic metabolic changes. (a) One of the major observations from these studies was that morphine treatment induces the production of significantly high amounts of coprostanol, a direct microbial conversion product of cholesterol in the intestine. There is a significant reduction in the abundance of primary bile acids, (b) CA and (c) chenodeoxycholic acid (CDCA) and (d) secondary bile acids deoxycholic acid (DCA) and (e) ursodeoxycholic acid (UDCA) in the fecal contents of morphine-treated mice. These affects are reversed in (a–e) morphine+naltrexone (NTX) treated and (f) TLR2KO animals. (g) Morphine induces significant accumulation of cholesterol in the liver, an effect, not seen in naltrexone-treated, μ-opioid receptor knockout (MORKO) and TLR2KO animals. (h) These changes in bile/cholesterol levels ultimately result in disrupted hepatoenteric circulation as shown by reduced recovery of UDCA in the liver. (i) Bile salt hydrolase (Bsh), one of the major bacterial enzymes, important for an efficient hepatoenteric circulation shows significantly reduced activity in the microbiome of morphine-treated animals. (j) Hence, as expected, a lower level of free taurine was observed in the fecal content of morphine-treated animals, with no significant changes in the TLR2KO animals. Also See Supplementary Figures S4 and S5. KO, knockout; TLR, toll-like receptor; WT, wild type. ‘o’ denotes extreme data point, ‘+’ denotes statistical mean. **p<0.05 compared to TLR2KO-morphine group.
