TY - JOUR
T1 - The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota
AU - Misawa, Noboru
AU - Higurashi, Takuma
AU - Takatsu, Tomohiro
AU - Iwaki, Michihiro
AU - Kobayashi, Takashi
AU - Yoshihara, Tsutomu
AU - Ashikari, Keiichi
AU - Kessoku, Takaomi
AU - Fuyuki, Akiko
AU - Matsuura, Tetsuya
AU - Ohkubo, Hidenori
AU - Usuda, Haruki
AU - Wada, Koichiro
AU - Naritaka, Nakayuki
AU - Takei, Hajime
AU - Nittono, Hiroshi
AU - Matsumoto, Mitsuharu
AU - Honda, Akira
AU - Nakajima, Atsushi
AU - Camilleri, Michael
N1 - Publisher Copyright:
© 2020 John Wiley & Sons Ltd
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Background: Elobixibat, a novel inhibitor of apical sodium-dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function. Aims: To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota. Methods: This was a prospective, single-centre study. After baseline period, patients received 10 mg daily of elobixibat for 2 weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration. Results: In the 30 patients analysed, the frequency of pre- and post-treatment bowel movements per fortnight was 7 and 10 (P < 0.001), respectively. The pre-treatment faecal bile acid concentration increased significantly from 10.9 to 15.0 µg/g stool post-treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94 µg/g stool to post-treatment 5.02 µg/g stool, P = 0.036) and in glycine-conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels. Conclusions: Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.
AB - Background: Elobixibat, a novel inhibitor of apical sodium-dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function. Aims: To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota. Methods: This was a prospective, single-centre study. After baseline period, patients received 10 mg daily of elobixibat for 2 weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration. Results: In the 30 patients analysed, the frequency of pre- and post-treatment bowel movements per fortnight was 7 and 10 (P < 0.001), respectively. The pre-treatment faecal bile acid concentration increased significantly from 10.9 to 15.0 µg/g stool post-treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94 µg/g stool to post-treatment 5.02 µg/g stool, P = 0.036) and in glycine-conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels. Conclusions: Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.
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U2 - 10.1111/apt.15950
DO - 10.1111/apt.15950
M3 - Article
C2 - 32687674
AN - SCOPUS:85088165938
SN - 0269-2813
VL - 52
SP - 821
EP - 828
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 5
ER -