Page 118 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 6
and FGF19 were lost at 1 week after placement. Bile acid levels were unchanged 1 week after placement, which supports the notion that the bile acid pool size may have increased gradually over time although metabolic improvements occurred immediately after placement [17]. This is in line with several studies performed in patients after RYGB surgery [12,20–23].
The DJBL-induced increase of bile acids was dependent on unconjugated bile acids, and more exaggerated compared to changes seen after RYGB surgery [12,21,23–25]. Dietary weight loss only marginally increases specific bile acids [26]. Hepatic conjugation of newly synthesized bile acids to occurs in the peroxisome, whereas re-conjugation of deconjugated bile acids occurs in the cytosol [27]. The reconjugation machinery is able to conjugate a potentially enlarged bile acid pool, as 99% of serum bile acids in patients treated with large doses of unconjugated ursodeoxycholate is conjugated [28]. Changes in the gut microbiome are possibly responsible for our results. Bacterial deconjugation is complete in the cecum and gut biotransformation of bile acids (i.e. ratios of CA: DCA and CDCA:LCA) were altered after 24 weeks [29]. The DJBL may have led to a different interplay between bile acids, gut bacteria and the gut lumen with effects on entero-endocrine hormones that regulate motility, transit and bile salt reabsorption via the apical sodium-dependent bile acid transporter (ASBT). This could result in increased deconjugation and increased colonic uptake not buffered by liver clearance [30]. The initial increase in unconjugated bile acids after DJBL placement may go unnoticed until the amount of unconjugated bile acids reaches a tipping point, exceeding liver clearance.
It has been suggested that the increase in plasma bile acids after RYGB surgery may be due to increased bile acid recirculation and FXR dependent transcriptional upregulation [31,32]. The former could be achieved by adaptive growth and concomitant increases in ASBT. However, previous studies after RYGB were not unequivocal [12,21,23–25].
The increased GLP-1 seems attributable to increased TGR5 signalling in the gut, although insulin secretion remained unchanged. Moreover, GLP-1 levels increased at week 1 whereas bile acid levels increased later which may be explained by an early increase of bile acids in the gut that were not yet noticeable peripherally. Indeed, our findings are in partial agreement with a previous study that examined
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