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. Author manuscript; available in PMC: 2015 Aug 12.
Published in final edited form as: Best Pract Res Clin Gastroenterol. 2014 Aug 12;28(4):727–740. doi: 10.1016/j.bpg.2014.07.016

Metabolic surgery: action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature

Timothy E Sweeney 1, John M Morton 1,*
PMCID: PMC4399638  NIHMSID: NIHMS677431  PMID: 25194186

Abstract

Obesity and type 2 diabetes remain epidemic problems. Different bariatric surgical techniques causes weight loss and diabetes remission to varying degrees. The underlying mechanisms of the beneficial effects of bariatric surgery are complex, and include changes in diet and behavior, as well as changes in hormones, bile acid flow, and gut bacteria. We summarized the effects of multiple different bariatric procedures, and their resulting effects on several hormones (leptin, ghrelin, adiponectin, glucagon-like peptide 1 (GLP-1), peptide YY, and glucagon), bile acid changes in the gut and the serum, and resulting changes to the gut microbiome. As much as possible, we have tried to incorporate multiple studies to try to explain underlying mechanistic changes. What emerges from the data is a picture of clear differences between restrictive and metabolic procedures. The latter, in particular the roux-en-Y gastric bypass, induces large and distinctive changes in most measured fat and gut hormones, including early and sustained increase in GLP-1, possible through intestinal bile acid signaling. The changes in bile flow and the gut microbiome are causally inseparable so far, but new studies show that each contributes to the effects of weight loss and diabetes resolution.

Keywords: Bariatric surgery, RYGB, hormone, bile acid, microbiome

Introduction

Obesity and type 2 diabetes are a worldwide epidemic. Medical weight loss through proper diet and exercise are essential to good health, but some patients require bariatric surgery in addition. Bariatric surgery has proven to be safe and effective in inducing weight loss and improving or even curing type 2 diabetes. Although all bariatric surgery procedures end up changing the patient’s diet, the alteration to patient anatomy and/or nutrient flow has effects that are independent of the restriction on diet.

Weight loss surgery can generally be divided into three classes: restrictive, metabolic, or both. The restrictive procedures discussed here are: the adjustable gastric band (AGB), which simply encircles the cardia of the stomach with an inflatable silicone ring; and the sleeve gastrectomy (SG), in which most of the greater curvature of the stomach is removed. After these procedures, nutrients follow their pre-surgical course, but the patient is limited in the rate of food intake. There are many metabolic procedures, some of which also include a restrictive component. Here we review several procedures, as their similarities and differences in anatomical rearrangement and downstream effect can be compared to draw insight into the underlying physiology. The duodenal-jejunal bypass (DJB) involves separating the duodenum from the stomach outlet, and connecting a jejunal limb in its place.. This procedure has a restrictive component; nutrients bypass the duodenum, which as a result is exposed to undiluted bile, and the bile and nutrients mix in the jejunum. Similar is the biliary-pancreatic diversion (BPD), which involves a much longer intestinal bypass, wherein the alimentary limb is anastomosed to the ileum. The BPD also usually involves a gastrectomy of varying types. BPD can lead to severe nutrient deficiencies, and is falling out of favor as RYGB and SG become more common (1, 2). Finally, the roux-en-Y gastric bypass (RYGB) involves separating the stomach into a small upper pouch, which is anastomosed to a roux jejunal limb, while leaving the remnant stomach attached to the biliary limb, into which the bile still drains. It is thus both restrictive and metabolic. The RYGB has been proven to induce greater weight loss and resolution of diabetes than the restrictive procedures, with a good safety record (3). Each weight loss intervention has its pros and cons; their various differences also induce different changes in patient physiology, leading to direct effects on weight loss and diabetes resolution.

The last 10–15 years has seen a great increase in research in the hormone environments of the gut and the adipose tissue as they relate to weight loss. The stomach and intestine are now known to be crucial in the production of hormones such as ghrelin and glucagon-like peptide (GLP)-1. Further, adipose tissue is under homeostatic control by leptin and adiponectin. Weight loss procedures all have differing effects on these and other hormones;RYGB, in particular, is known to have an incretin effect, through both the ‘foregut’ mechanism, whereby bypass of the proximal small intestine leads to decreased anti-incretin effects, and the ‘hindgut’ mechanism, whereby direct flow nutrients to the distalsmall bowel cause a direct increase in incretin hormones. Disentangling the surgical changes from the changes induced by weight loss and diet are keys to understanding both the underlying physiology of obesity as well as the success of bariatric surgery.

Metabolic bariatric surgery has long been known to exert at least some of its effects through altered bile flow, including decreased absorption of fatty acids and increased bile production by the liver. Bile acids are now understood as signaling molecules in their own right; mechanistic studies of oral bile acid sequestrants have shown a significant incretin effect from altered bile flow (4). Mechanistic studies of bile flow after surgery are difficult, and only few have been accomplished. Still, new evidence points to a causal link between the altered bile flow in malabsorptive procedures and the subsequent incretin effect.

The alterations in diet and bile flow that accompany weight loss surgery lead to changes in the gut microbiome. The techniques that are now used to profile the gut microbiome are relatively new, so mechanistic studies of bariatric surgery and changes in gut bacteria are only now beginning to come out (5). Studies of the microbiome after change in diet, weight loss, bariatric surgery, probiotics, and antibiotics have all given new insights into how changes in the gut bacteria lead to profound changes in host physiology.

Here, we report a review of the impact of known weight loss procedures on gut and adipose hormones, bile acids, and the gut microbiome. From the large body of research that has been amassed, we can begin to glean new insights into the mechanism of weight loss and diabetes resolution after weight loss surgery.

Methods

A review of the mechanisms of bariatric surgery and medical weight loss was undertaken. Pubmed was hand-searched for the following interventions: gastric band or gastric banding or AGB; sleeve gastrectomy or SG; duodenal bypass or duodenojejunal bypass or DJB; roux en Y gastric bypass or gastric bypass or RYGB; biliary pancreatic diversion or biliopancreatic diversion or BPD; and bile acid sequestrant or colestipol or cholestyramine or colesevelam. Each intervention was searched with the following terms: hormone; leptin; ghrelin; adiponectin; glucagon; GLP-1; peptide YY or PYY; or serum bile acid or bile acids; and microbiome or microbiota. Medical weight loss was searched with: medical weight loss or restrictive diet weight loss. As this review is intended to focus on bariatric surgical interventions, the medical weight loss review was not designed to be comprehensive.

This list generated several hundred articles. We excluded reviews or studies not done in humans, with the exception of some mechanistic studies of bile acid sequestrants and the gut microbiome, where human data are sparse. Studies that did not provide adequate statistical comparisons between groups (ie, studies that showed trends without tests) were not included. Also not included were studies that did not group patients according to a single intervention (ie, grouped several surgery types together). Trends that did not achieve statistical significance were listed as ‘no change’. For time-course measurements, achievement of a statistical difference at any time point was listed as a change (ie, measurements at 3,6, and 12 months that were significantly increased only at 12 months were listed as ‘increased’), unless there were significant changes in opposite directions during the time course. Due to the significant amount of literature present in this field, some studies may have been missed.

Results

Hormonal changes in weight loss and bariatric surgery

Energy homeostasis and fat metabolism in the body are heavily regulated by a complex network of hormones (6, 7). A relatively small subset of hormones has been thoroughly studied in the setting of bariatric surgery (leptin, ghrelin, adiponectin, glucagon-like peptide 1 (GLP-1), glucagon, and peptide YY (PYY)), and we will focus on this subset. This list is not comprehensive; however, each hormone included in this review has data available across most surgical interventions. Each hormone will be discussed in turn; Table 1 shows the literature findings of hormone changes across the various interventions.

Table 1.

Review of studies on hormonal changes across different interventions. If one group of studies formed a majority, the number is listed, and their references are found in the cell at right.

Leptin Ghrelin Adiponectin GLP-1 Glucagon PYY
Medical
Weight
Loss 		Decrease (26, 47, 52, 58, 109),
No Change (55)		 No Change (46, 47, 54, 55),
Increase (35, 52, 53, 58)		 Decrease (85),
No Change (55),
Increase (47, 64, 67, 85)		 Decrease (58),
No Change (54, 55, 71, 87–90)		 Decrease (109–111) Decrease (58),
No Change (52, 53, 55, 87)
AGB Decrease (9–28),
No Change (29,30),
Immediate
Increase (31,32),
Late Increase (8,33,34)		 Decrease (34)
No Change (8, 14, 20, 21, 29, 56, 57),
Transient Increase (16),
Increase (11, 25, 27, 51),
Late Increase (10)		 Increase (17, 19, 22, 28, 33, 65, 68) No Change (8, 20, 21, 56, 57, 68, 91–93),
Increased Less Than RYGB (29)		 No Change (68, 91, 93) No Change (8, 56, 57)
Decreased fasting level,
Increased total production (27, 92, 114),
Increased Less Than RYGB (20, 29)
SG Decrease (40, 41, 43, 47, 49, 73, 75, 77) Immediate Decrease (97)
Decrease (35–38, 40, 41, 44–49),
Late Decrease (42),
No Change (43)		 Increase (41, 45, 47, 73, 77) Decrease (44),
No Change (90)
Increase Less
Than RYGB (37, 39, 49),
Increase (38, 40, 42, 48, 89, 94, 95, 97)		 Late Decrease (44, 112),
Early Increase (42, 94)		 Early Decrease (44)
No Change (41,42),
Increase Less
Than RYGB (37–40);
Increase (97, 115)
RYGB Decrease (8, 11, 20, 26, 29, 33, 43, 49, 72, 74, 77) Decrease (37, 38, 42, 54, 56),
No Change (8, 11, 20, 35, 43, 49, 57),
Higher than SG (61),
Increase (62, 74, 76)		 Increase (29, 33, 45, 68–71, 74–79, 81–84) Decrease (92),
Increase (8, 20, 37–39, 42, 49, 50, 56, 57, 68, 71, 84, 87, 90, 91, 94–96)		 No Change (91)
Increase (68, 94, 110, 113)		 Increase (20, 29, 37–39, 49, 56, 57, 87, 92, 96),
Late Increase (8, 42)
BPD Decrease (23, 72, 73) Decrease (59),
No Change (44)		 Increase (73) Early Increase (44) Early Increase (44) Increase (44)
DJB Decrease (86) Decrease (60)
No Change (36)		 No Change (86) Increase (36, 61, 86, 116) Decrease (86)
Increase (61)		 Increase (116)
Bile Acid
Sequestrants 		not studied not studied not studied No Change (104),
Increased in Humans (98–100),
Increased in Rodents (101–103)		 No Change (98–100) Decreased (117),
No Change (104), Increased in rats (101)
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Leptin is a hormone made in adipose tissue and increased by increased fat mass; its main function is to decrease hunger. When a person loses fat mass by any means, the level of circulating leptin falls, thereby triggering a hunger response at the hypothalamus. Thus, leptin normally acts to keep fat mass constant. Since all reviewed interventions lead to weight loss, it is perhaps not surprising that all have evidence of late decrease in leptin levels, perhaps in rough proportion to the amount of weight lost (i.e., leptin levels decrease less with AGB than RYGB, and total weight loss follows the same trend, (8)). Interestingly, AGB is the only procedure which has repeated measures of increases in leptin (which would thereby function to decrease hunger in such patients). Although 21 of 27 studies still report a decline in leptin in patients post-AGB (9–29), there are several papers which show either no change (30, 31), an immediate increase (32, 33), or a late increase (8, 34). Our literature review did not turn up any similar increases in leptin in other bariatric interventions. Why a small proportion of the literature would show an increase (as opposed to simply no change) in AGB is unclear, and an open question.

Ghrelin is a hormone that is a cleavage product of preproghrelin, along with obestatin (31). Ghrelin’s best-known function is to stimulate hunger, somewhat opposite of leptin. Preproghrelin is made mainly in the stomach (31); thus it might be expected that removal of part of the stomach might decrease ghrelin, and indeed, we see such an effect with SG. A total of 14 out of 15 studies of ghrelin levels after SG show a significant decrease (35–49). In contrast, both medical weight loss and AGB show either no change or an increase in ghrelin, thereby stimulating hunger (8, 10, 11, 14, 16, 20–22, 26, 28, 46, 47, 50–58). Malabsorptive procedures all show mixed data, indicating that nutrient flow likely alters ghrelin production to some degree. BPD (44, 59) and DJB (36, 60) each show either a decrease in ghrelin or no change. Studies of ghrelin after RYGB exhibit the full range of responses: decreased, unchanged, and increased (8, 11, 21, 35, 37–39, 43, 49, 54, 56, 57, 61, 62). There can be considerable variation in ghrelin levels based on timing of blood draw with relation to surgery, operative technique, and remnant gastric pouch; these may partly explain the mixed nature of these results. These data suggest that ghrelin production is decreased at least in part by altered upper GI nutrient flow, though this mechanism may be indirect.

Adiponectin is a complex hormone that has a variety of actions. Briefly, although it is produced by adipose tissue, its circulating level has been found to negatively correlate to BMI (63). Adiponectin is involved in energy homeostasis and insulin sensitivity. A literature review shows that adiponectin is almost universally increased after bariatric surgery or medical weight loss (17, 19, 23, 29, 34, 41, 45, 47, 50, 55, 64–84). Moreover, no study showed an increase in adiponectin due to a given procedure not also possibly explained by weight loss. The only studies which did not show a change in adiponectin were one showing a decrease in adiponectin after medical weight loss (85) and a study of duodenal-jejunal bypass in which the surgical group did not show a significant change in fat mass or BMI (86). It thus seems most likely that adiponectin production is increased secondary to weight loss in all procedures, since it is increased by weight loss of any kind, including medical weight loss.

GLP-1 is a hormone that is made in the ileum. As an incretin, it is known to increase insulin production and decrease glucagon production. The GLP-1 analogues exenatide and liraglutide are used in the treatment of type 2 diabetes. Six studies have shown that GLP-1 is not increased after medical weight loss and may be decreased (54, 55, 71, 87–90). Only 1 of 10 studies in AGB showed an increase in GLP-1, and in that one study it was increased less than RYGB (30); the others showed no change (8, 21, 22, 56, 57, 68, 91–93). Every malabsorptive procedure exhibits an increase in GLP-1 (for a discussion of the impact of bile acids on GLP-1, see the section below). RYGB has been especially well-studied with 19 of 20 studies showing an increase in GLP-1 after RYGB (8, 21, 37–39, 42, 49, 50, 56, 57, 68, 71, 84, 87, 90, 91, 94–96), and only 1 study showing a decrease (92). The increase in GLP-1 has been shown to occur prior to weight loss, and may contribute to the early remission of diabetes (84). Interestingly, GLP-1 showed variable response to SG, with studies showing GLP-1 decrease (44), no change (90), an increase less than RYGB (37, 39, 49), or an overall increase (38, 40, 42, 48, 89, 94, 95, 97). The preponderance of the evidence suggests that SG increases GLP-1; since simple restriction in the setting of diet or AGB does not increase GLP-1, this seems to be specific to the removal of a portion of the stomach, though still could be a secondary effect. Overall, one clear contribution of altered anatomy in bariatric surgery is an incretin effect due to increased GLP-1.

The effects of bile acid on GLP-1 are important in the outcomes of bariatric surgery. Pharmacologic bile acid sequestration (via colestipol, cholestyramine, or colesevelam) has been shown to increase circulating GLP-1 levels and reduce hyperglycemia in both humans (98–100) and rodents (101–103). One study showed no change in incretins due to colesevelam, though there was still an improvement in oral, but not intravenous, glucose tolerance (104). The bile acid sequestrants all decrease serum bile acids (not surprisingly) (105–107), while the malabsorptive procedures increase them (see bile acids section and Table 2 below). The common mechanism of action, if one exists, is thus likely the alteration of bile flow in the intestine, but this has not been proved. One elegant study showed that enteric bile acids signal through the receptor TGR-5 in the intestine to increase GLP-1 production (108). Overall, these data show that altered bile acid flow in malabsorptive procedures is likely one reason for their resultant incretin effect. Still, Steinert et al. showed that increases in serum bile acid after RYGB lagged behind the increase in GLP-1 by several months (95); clearly, more work is needed to elucidate the exact mechanism.

Table 2.

Review of studies on bile acid changes across interventions.

Serum Bile Acids
Medical
Weight Loss
(late) 		Decreased postprandial in obesity (118)
Higher in obesity, Decreased during weight loss (119–121)
AGB Decreased (123),
No Change (57),
Increased in AGB+SG (122)
SG Early Decrease (95);
No Change (41);
Increased in AGB + SG (122)
RYGB Increase (57, 96, 123–129);
Initial Decrease, late Increase (95)
BPD Not studied
DJB Not studied
Bile Acid
Sequestrants 		Decreased (105–107)
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Glucagon functions opposite insulin to increase circulating glucose via decreased uptake and increased glycogenolysis. Generally, glucagon levels are not well studied after bariatric surgery. The studies that have been done show somewhat conflicting results; there may be a trend towards increased glucagon production after malabsorptive procedures. Patients undergoing medical weight loss show decreased glucagon production (109–111). After AGB there is no change in glucagon production (68, 91, 93), and after SG there is evidence of both early increase (42, 94) and late decrease (44, 112). With the exception of one study showing no change (91), both BPD and RYGB show evidence of increased glucagon production (44, 68, 94, 110, 113). BPD and RYGB methods also tend to have the highest increases in insulin; it is possible that the increased glucagon observed after RYGB and BPD are compensatory increases for significantly lowered blood sugar in these cases.

Peptide YY is released by the ileum and colon and is known to inhibit gastric motility, reduce pancreatic exocrine secretion, and may reduce appetite directly through NPY receptors in the brain. It also may inhibit appetite through secondary effects of reduced GI motility. Studies have shown that PYY either decreases (58) or does not change after medical weight loss (52, 53, 55, 87). Both AGB and SG show a general trend towards increased PYY, with 18 studies reporting a range of decreased (44), unchanged (8, 41, 42, 56, 57), and increased (21, 28, 37–40, 49, 50, 92, 97, 114, 115) PYY after intervention. Interestingly, the malabsorptive procedures show a uniform increase in PYY (8, 21, 30, 37–39, 42, 44, 49, 56, 57, 87, 92, 96, 116). The mechanism of how PYY is increased is unclear, but may be related to early contact with nutrients or altered bile flow; bile acid sequestration shows mixed effects for PYY (decreased (117), no change (104), increased in rats (101)). The overall effect on PYY on weight loss and diabetes resolution is thus unclear, but appetite reduction due to increased PYY may contribute to the anti-obesity effects of malabsorptive procedures.

Bile acid changes in bariatric surgery

The normal enterohepatic circulation is that primary conjugated bile acids are secreted into the duodenum in response to fatty meals, where they mix with fatty acids. Some are dehydroxylated to secondary bile salts by lower GI bacteria. Most are reabsorbed in the ileum and flow back to the liver. The level of postprandial bile excretion is decreased in obese compared to lean patients (118); serum bile acids are higher in obesity, and decrease after medical weight loss (119–121). The studies done in AGB and SG are conflicting, showing serum bile acid levels that are increased (122), decreased (95, 123), and unchanged (41, 57) in response to restrictive procedures. No serum bile acid data could be found for DJB or BPD. In RYGB, 9 of 10 studies showed in increase in some fraction of serum bile acids (57, 96, 123–129); the other study showed an initial decrease prior to a late increase (95) (see Table 2 for references). Overall, the increased serum bile acids seen in RYGB are well-known, and the increase is believed to be due to the fact that excreted bile acids have less time to mix with food prior to transit through the ileum, leaving more bile acids free for ileal reuptake. See Table 2 for an overview of alterations in bile flow in bariatric surgery.

As discussed above, increased free ileal bile acids activate TGR-5, leading to increased GLP-1 production. A separate incretin effect from bile follows the bile->FXR->FGF-19->CYP7A1 pathway (130). Briefly, luminal bile acids bind the Farnesoid X Receptor (FXR) in the intestine, which activates fibroblast growth factor (FGF)-19; FGF-19 then activates CYP7A1 in the liver, which produces bile acid from cholesterol; it is thus a somewhat rare example of a feed-forward mechanism. FGF-19 is decreased in diabetes; after RYGB, it was shown that both FGF-19 expression and bile acid production increase to a greater degree in diabetic patients, possibly contributing to the increased bile acid levels and hence the incretin effect of RYGB (126, 131). On the other hand, some data suggest that FGF-19 is not increased by RYGB (128). Interestingly, FGF-19 was previously found to be decreased by bile acid sequestrants and increased by oral bile acid supplementation (132); this FGF-19 pathways is thus somewhat at odds with the finding of an incretin effect with bile acid sequestrants.

Increased bile acids have a complex relationship with gut microbiota. An increase in free bile acids may encourage overgrowth of bile-tolerant bacteria in phylum proteobacter (such as Bilophila wadsworthia); at the same time, a change in gut bacteria may change the degree to which bile acids are metabolized in the gut (133). Moreover, some evidence shows that the gut microbiota directly regulate the production of bile acids by conjugating bile acids to activate FXR->FGF signaling (134). Sorting out the cause and effect of change in bile acid flow and change in gut bacteria remains an active area of study.

Gut microbiota changes in bariatric surgery

The gut microbiome changes significantly after both medical weight loss and bariatric surgery (5). In particular, recent research has repeatedly shown persistent phyla-level differences in obesity, and after medical weight loss and RYGB. Generally, the Firmicutes:Bacteroides ratio is increased in obese individuals (135–138), and decreases after medical weight loss (135, 139, 140), though one study reported no significant difference between healthy and obese patients (141). A similar decrease in the Firmicutes:Bacteroides ratio is induced after RYGB (138, 142, 143). Moreover, several studies have now shown an increase in Proteobacteria after RYGB (142–145). Unfortunately, our comprehensive literature search found no studies of the microbiome in any of the other interventions discussed here.

The taxonomic changes observed after medical weight loss and after RYGB have in common a decreased Firmicutes:Bacteroides ratio; however, RYGB shows a persistent increase in Proteobacter that is not observed in medical weight loss. Moreover, David et al. showed that a change in diet to less carbohydrates and higher protein and fat produced a very fast (within a day) significant shift towards increased gut bile-tolerant phylum Proteobacter (133). One possibility is thus that RYGB patients ingest more animal products than their medical weight loss counterparts, and this induces a shift towards Proteobacteria. However, a more likely scenario is that the greater amount of free bile acids seen by the lower intestine after RYGB creates an environment more hospitable to bile-tolerant bacteria such as in phylum Proteobacter. Perhaps even more fascinating is that a recent study of the gut microbiome after oral vancomycin administration showed that the vancomycin selectively killed off Firmicutes bacteria, which lead to an overgrowth of Proteobacter; this in turn caused a decrease in secondary bile acids, leading to increased serum primary bile acid levels with a resulting incretin effect (146). Putting these data together, then, the increase in free primary bile acids in the lower intestine after RYGB has both a direct incretin effect through TGR-5 signalling, but also an indirect feedforward effect in serum bile acids caused by changes in the gut microbiome. These synergistic changes may be partly responsible for the magnified incretin effect seen after RYGB. As an aside, it should also be noted that a recent study linked increased Proteobacter to a higher incidence of gallstones; thus changes in the gut microbiome may also be linked to the increase in gallstones after RYGB (147). Finally, it has also been shown that administering oral lactobacillus post-RYGB leads to increased weight loss; there may thus be benefits to modulating gut microbiota to induce weight loss (148).

A mechanistic proposal of interplay between hormones, bile, and the microbiome

Taken together, the complex interplay between change in diet, bile flow alteration, hormonal change and altered gut microbiota cannot be easily understood. Still, some cause and effect relationships are clear, even if the exact mechanisms remain unknown. First, leptin is decreased and adiponectin is increased in rough proportion to weight loss, and they do not appear to change according to type of intervention. Second, SG is the only intervention which appears to show a sustained decrease in ghrelin, and this may be partly responsible for its greater weight loss success than AGB. Third, some of the anorectic effect seen in malabsorptive procedures may be due to increases in PYY. Fourth, GLP-1 is significantly increased in malabsorptive procedures, at least partially due to a direct effect from increased unbound luminal bile acids acting through intestinal TGR-5. Moreover, the incretin effect from GLP-1 can be reproduced in part by oral administration of bile acid sequestrants. Fifth, RYGB causes an increase in free bile acids in the lower intestine and increases in serum bile acids not seen with restrictive procedures or medical weight loss; this may contribute to its incretin effect through TGR-5 signalling to increase GLP-1 expression. Finally, RYGB induces an increase in Proteobacter in the gut microbiome not seen in medical weight loss, and this may induce a feedforward mechanism towards increasing serum bile acids and an incretin effect.

In each intervention discussed here, the diet is changed. Moreover, the diets between the different interventions may be changed in different ways; malabsorptive procedures, in particular, often create an aversion to dietary fats. The effects discussed above thus cannot be untangled, as of yet, from their possible dietary changes. Still, some elegant mechanistic studies of bile flow, gut bacteria and incretins have helped explain, at least in part, why malabsorptive procedures are so successful in reversing type 2 diabetes.

Weaknesses

This review has some weaknesses. First, the exact time courses of the changes in hormones with respect to the procedures are not reviewed here. Second, the choice of hormones reviewed is not comprehensive. The actions of other hormones, such as insulin, thyroid hormones, GIP, and FGF-19 were not reviewed. Third, medical weight loss was not reviewed systematically, and so our results may have bias. Finally, this study is not a formal meta-analysis; although we aimed to be comprehensive in our literature search, simple ‘vote-counting’ of studies should not take the place of a formal statistical meta-analysis; we hope that others will use this work as a starting point for more formal analyses.

Conclusions

Obesity and type 2 diabetes remain as epidemics. Modern bariatric surgery is safe, reliable, and effective for weight loss and reduction of insulin resistance. While both restrictive and malabsorptive procedures are effective for weight loss, RYGB in particular is known to induce greater weight loss with a higher cure rate of type 2 diabetes. The so-called BRAVE effects of RYGB (altered Bile flow due to exclusion of the biliary limb, Reduced gastric size in the RYGB , Anatomic gut rearrangement (as explained in the introduction), Vagal alterations secondary to the gut rearrangement, and Enteric hormone alterations as reviewed here) have been known for some time, but only recently have mechanistic studies in bile flow and gut microbiota shed light on how RYGB causes such a significant incretin effect.

Still, more work is needed. Important questions include whether and how the gut microbiome might change in purely restrictive procedures, and to what degree this depends on diet. Also important to reconcile is the exact mechanism of action of bile acids in the incretin effect; although intestinal TGR-5 signaling may cause at least part of this effect, it doesn’t explain why bile acid sequestrants and anatomic bile-rerouting both have an incretin effect through GLP-1. Regarding hormonal changes, enough studies have been done that a formal meta-analysis of hormonal changes after bariatric surgery, including time series, would be both feasible and beneficial. As the questions of timing of changes in diet, hormones, bile flow, gut bacteria, and weight loss become clear, causative models will be established, giving unparalleled insight into the physiology of obesity and weight loss.

Table 3.

Review of studies on gut microbiome changes across different interventions.

Gut Microbiota
Obesity
vs
Normal		 Firmicutes:Bacteroides ratio increased in obesity (135–138),
No change in phyla (141)
Medical
Weight
Loss		 F:B ratio decreased after weight loss (135, 139, 140)
Diet profoundly changes microbiome (133)
AGB Not Studied
SG Not Studied
Post-
RYGB		 F:B ratio decreased (138, 142, 143);
Administration of lactobacillus increases weight loss (148);
Proteobacter increased (142–145)
BPD Not Studied
DJB Not Studied
Bile Acid
Sequestrants		 Not Studied
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Practice Points.

  • Bariatric surgery is now recognized as having profound metabolic effects.

  • Comparative effectiveness of bariatric surgery varies with gastric bypass providing the most effectiveness and gastric band the least effectiveness with corresponding metabolic changes

  • Changes in the microbiome and their role in weight loss following bariatric surgery require more definition

Research Agenda.

  • The role of the microbiome, bile acid metabolism, and hormonal changes following bariatric surgery needs to be further defined.

  • The impact of the microbiome upon weight loss should be determined to be associative or causative.

  • The mechanism of bile acid metabolism upon weight changes requires further study.

Footnotes

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References

  • 1.Topart P, Becouarn G, Sallé A, Ritz P. Biliopancreatic diversion requires multiple vitamin and micronutrient adjustments within 2 years of surgery. Surg Obes Relat Dis. 2014 doi: 10.1016/j.soard.2014.02.007. [DOI] [PubMed] [Google Scholar]
  • 2.Santry HP, Gillen DL, Lauderdale DS. Trends in bariatric surgical procedures. JAMA. 2005;294(15):1909–1917. doi: 10.1001/jama.294.15.1909. [DOI] [PubMed] [Google Scholar]
  • *3.Flum DR, Belle SH, King WC, Wahed AS, Berk P, Chapman W, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445–454. doi: 10.1056/NEJMoa0901836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Holst JJ, McGill MA. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes mellitus: focus on bile acid sequestrants. Clin Drug Investig. 2012;32(1):1–14. doi: 10.2165/11595370-000000000-00000. [DOI] [PubMed] [Google Scholar]
  • 5.Sweeney TE, Morton JM. The human gut microbiome: a review of the effect of obesity and surgically induced weight loss. JAMA Surg. 2013;148(6):563–569. doi: 10.1001/jamasurg.2013.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • *6.Breen DM, Rasmussen BA, Côté CD, Jackson VM, Lam TK. Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes. Diabetes. 2013;62(9):3005–3013. doi: 10.2337/db13-0523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Lancha A, Frühbeck G, Gómez-Ambrosi J. Peripheral signalling involved in energy homeostasis control. Nutr Res Rev. 2012;25(2):223–248. doi: 10.1017/S0954422412000145. [DOI] [PubMed] [Google Scholar]
  • 8.Korner J, Inabnet W, Febres G, Conwell IM, McMahon DJ, Salas R, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond) 2009;33(7):786–795. doi: 10.1038/ijo.2009.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Infanger D, Baldinger R, Branson R, Barbier T, Steffen R, Horber FF. Effect of significant intermediate-term weight loss on serum leptin levels and body composition in severely obese subjects. Obes Surg. 2003;13(6):879–888. doi: 10.1381/096089203322618704. [DOI] [PubMed] [Google Scholar]
  • 10.Hanusch-Enserer U, Cauza E, Brabant G, Dunky A, Rosen H, Pacini G, et al. Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding. J Clin Endocrinol Metab. 2004;89(7):3352–3358. doi: 10.1210/jc.2003-031438. [DOI] [PubMed] [Google Scholar]
  • 11.Stoeckli R, Chanda R, Langer I, Keller U. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res. 2004;12(2):346–350. doi: 10.1038/oby.2004.43. [DOI] [PubMed] [Google Scholar]
  • 12.Uzun H, Zengin K, Taskin M, Aydin S, Simsek G, Dariyerli N. Changes in leptin, plasminogen activator factor and oxidative stress in morbidly obese patients following open and laparoscopic Swedish adjustable gastric banding. Obes Surg. 2004;14(5):659–665. doi: 10.1381/096089204323093453. [DOI] [PubMed] [Google Scholar]
  • 13.Coupaye M, Bouillot JL, Coussieu C, Guy-Grand B, Basdevant A, Oppert JM. One-year changes in energy expenditure and serum leptin following adjustable gastric banding in obese women. Obes Surg. 2005;15(6):827–833. doi: 10.1381/0960892054222768. [DOI] [PubMed] [Google Scholar]
  • 14.Dixon AF, Dixon JB, O'Brien PE. Laparoscopic adjustable gastric banding induces prolonged satiety: a randomized blind crossover study. J Clin Endocrinol Metab. 2005;90(2):813–819. doi: 10.1210/jc.2004-1546. [DOI] [PubMed] [Google Scholar]
  • 15.Heinonen MV, Purhonen AK, Miettinen P, Pääkkönen M, Pirinen E, Alhava E, et al. Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regul Pept. 2005;130(1–2):7–13. doi: 10.1016/j.regpep.2005.05.003. [DOI] [PubMed] [Google Scholar]
  • 16.Mariani LM, Fusco A, Turriziani M, Veneziani A, Marini MA, de Lorenzo A, et al. Transient increase of plasma ghrelin after laparoscopic adjustable gastric banding in morbid obesity. Horm Metab Res. 2005;37(4):242–245. doi: 10.1055/s-2005-861410. [DOI] [PubMed] [Google Scholar]
  • 17.Poitou C, Lacorte JM, Coupaye M, Bertrais S, Bedel JF, Lafon N, et al. Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and after gastric banding surgery. Obes Surg. 2005;15(1):11–23. doi: 10.1381/0960892052993431. [DOI] [PubMed] [Google Scholar]
  • 18.Ram E, Vishne T, Maayan R, Lerner I, Weizman A, Dreznik Z, et al. The relationship between BMI, plasma leptin, insulin and proinsulin before and after laparoscopic adjustable gastric banding. Obes Surg. 2005;15(10):1456–1462. doi: 10.1381/096089205774859146. [DOI] [PubMed] [Google Scholar]
  • 19.Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab. 2006;91(4):1578–1581. doi: 10.1210/jc.2005-2248. [DOI] [PubMed] [Google Scholar]
  • 20.Knerr I, Herzog D, Rauh M, Rascher W, Horbach T. Leptin and ghrelin expression in adipose tissues and serum levels in gastric banding patients. Eur J Clin Invest. 2006;36(6):389–394. doi: 10.1111/j.1365-2362.2006.01642.x. [DOI] [PubMed] [Google Scholar]
  • 21.le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243(1):108–114. doi: 10.1097/01.sla.0000183349.16877.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Shak JR, Roper J, Perez-Perez GI, Tseng CH, Francois F, Gamagaris Z, et al. The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones. Obes Surg. 2008;18(9):1089–1096. doi: 10.1007/s11695-008-9454-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S, et al. Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol. 2009;51(4):765–777. doi: 10.1016/j.jhep.2009.06.016. [DOI] [PubMed] [Google Scholar]
  • 24.Alam I, Stephens JW, Fielding A, Lewis KE, Lewis MJ, Baxter JN. Temporal changes in glucose and insulin homeostasis after biliopancreatic diversion and laparoscopic adjustable gastric banding. Surg Obes Relat Dis. 2012;8(6):752–763. doi: 10.1016/j.soard.2011.10.018. [DOI] [PubMed] [Google Scholar]
  • 25.Krieger AC, Youn H, Modersitzki F, Chiu YL, Gerber LM, Weinshel E, et al. Effects of laparoscopic adjustable gastric banding on sleep and metabolism: a 12-month follow-up study. Int J Gen Med. 2012;5:975–981. doi: 10.2147/IJGM.S35566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Med. 2013;104(3):309–316. [PubMed] [Google Scholar]
  • 27.Lips MA, Pijl H, van Klinken JB, de Groot GH, Janssen IM, Van Ramshorst B, et al. Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects. Eur J Endocrinol. 2013;169(3):339–347. doi: 10.1530/EJE-13-0339. [DOI] [PubMed] [Google Scholar]
  • 28.Sysko R, Devlin MJ, Schebendach J, Tanofsky-Kraff M, Zimmerli E, Korner J, et al. Hormonal responses and test meal intake among obese teenagers before and after laparoscopic adjustable gastric banding. Am J Clin Nutr. 2013;98(5):1151–1161. doi: 10.3945/ajcn.113.061762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Urbanavičius V, Abalikšta T, Brimas G, Abraitienė A, Gogelienė L, Strupas K. Comparison of changes in blood glucose, insulin resistance indices, and adipokine levels in diabetic and nondiabetic subjects with morbid obesity after laparoscopic adjustable gastric banding. Medicina (Kaunas) 2013;49(1):9–14. [PubMed] [Google Scholar]
  • 30.Bose M, Machineni S, Oliván B, Teixeira J, McGinty JJ, Bawa B, et al. Superior appetite hormone profile after equivalent weight loss by gastric bypass compared to gastric banding. Obesity (Silver Spring) 2010;18(6):1085–1091. doi: 10.1038/oby.2009.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J. 2004;18(3):439–456. doi: 10.1096/fj.03-0641rev. [DOI] [PubMed] [Google Scholar]
  • 32.Frühbeck G, Diez-Caballero A, Gómez-Ambrosi J, Gil MJ, Monreal I, Salvador J, et al. Disruption of the leptin-insulin relationship in obese men 24 hours after laparoscopic adjustable silicone gastric banding. Obes Surg. 2002;12(3):366–371. doi: 10.1381/096089202321088174. [DOI] [PubMed] [Google Scholar]
  • 33.Maruna P, Gürlich R, Fried M, Frasko R, Chachkhiani I, Haluzik M. Leptin as an acute phase reactant after non-adjustable laparoscopic gastric banding. Obes Surg. 2001;11(5):609–614. doi: 10.1381/09608920160556814. [DOI] [PubMed] [Google Scholar]
  • 34.Trakhtenbroit MA, Leichman JG, Algahim MF, Miller CC, Moody FG, Lux TR, et al. Body weight, insulin resistance, and serum adipokine levels 2 years after 2 types of bariatric surgery. Am J Med. 2009;122(5):435–442. doi: 10.1016/j.amjmed.2008.10.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kotidis EV, Koliakos GG, Baltzopoulos VG, Ioannidis KN, Yovos JG, Papavramidis ST. Serum ghrelin, leptin and adiponectin levels before and after weight loss: comparison of three methods of treatment--a prospective study. Obes Surg. 2006;16(11):1425–1432. doi: 10.1381/096089206778870058. [DOI] [PubMed] [Google Scholar]
  • 36.Li F, Zhang G, Liang J, Ding X, Cheng Z, Hu S. Sleeve gastrectomy provides a better control of diabetes by decreasing ghrelin in the diabetic Goto-Kakizaki rats. J Gastrointest Surg. 2009;13(12):2302–2308. doi: 10.1007/s11605-009-0997-1. [DOI] [PubMed] [Google Scholar]
  • 37.Peterli R, Wölnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–241. doi: 10.1097/SLA.0b013e3181ae32e3. [DOI] [PubMed] [Google Scholar]
  • 38.Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C, Gass M, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740–748. doi: 10.1007/s11695-012-0622-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Ramón JM, Salvans S, Crous X, Puig S, Goday A, Benaiges D, et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J Gastrointest Surg. 2012;16(6):1116–1122. doi: 10.1007/s11605-012-1855-0. [DOI] [PubMed] [Google Scholar]
  • 40.Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study. Ann Surg. 2013;257(4):647–654. doi: 10.1097/SLA.0b013e31826e1846. [DOI] [PubMed] [Google Scholar]
  • 41.Haluzíková D, Lacinová Z, Kaválková P, Drápalová J, Křížová J, Bartlova M, et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity (Silver Spring) 2013;21(7):1335–1342. doi: 10.1002/oby.20208. [DOI] [PubMed] [Google Scholar]
  • 42.Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab. 2013;98(11):4391–4399. doi: 10.1210/jc.2013-2538. [DOI] [PubMed] [Google Scholar]
  • 43.Terra X, Auguet T, Guiu-Jurado E, Berlanga A, Orellana-Gavaldà JM, Hernández M, et al. Long-term changes in leptin, chemerin and ghrelin levels following different bariatric surgery procedures: Roux-en-Y gastric bypass and sleeve gastrectomy. Obes Surg. 2013;23(11):1790–1798. doi: 10.1007/s11695-013-1033-9. [DOI] [PubMed] [Google Scholar]
  • 44.Tsoli M, Chronaiou A, Kehagias I, Kalfarentzos F, Alexandrides TK. Hormone changes and diabetes resolution after biliopancreatic diversion and laparoscopic sleeve gastrectomy: a comparative prospective study. Surg Obes Relat Dis. 2013;9(5):667–677. doi: 10.1016/j.soard.2012.12.006. [DOI] [PubMed] [Google Scholar]
  • 45.Carrasco F, Basfi-Fer K, Rojas P, Valencia A, Csendes A, Codoceo J, et al. Changes in bone mineral density after sleeve gastrectomy or gastric bypass: relationships with variations in vitamin D, ghrelin, and adiponectin levels. Obes Surg. 2014;24(6):877–884. doi: 10.1007/s11695-014-1179-0. [DOI] [PubMed] [Google Scholar]
  • 46.Malin SK, Samat A, Wolski K, Abood B, Pothier CE, Bhatt DL, et al. Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy. Int J Obes (Lond) 2014;38(3):364–370. doi: 10.1038/ijo.2013.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Palikhe G, Gupta R, Behera BN, Sachdeva N, Gangadhar P, Bhansali A. Efficacy of laparoscopic sleeve gastrectomy and intensive medical management in obese patients with type 2 diabetes mellitus. Obes Surg. 2014;24(4):529–535. doi: 10.1007/s11695-013-1114-9. [DOI] [PubMed] [Google Scholar]
  • 48.Umemura A, Sasaki A, Nitta H, Otsuka K, Suto T, Wakabayashi G. Effects of changes in adipocyte hormones and visceral adipose tissue and the reduction of obesity-related comorbidities after laparoscopic sleeve gastrectomy in Japanese patients with severe obesity. Endocr J. 2014;61(4):381–391. doi: 10.1507/endocrj.ej13-0524. [DOI] [PubMed] [Google Scholar]
  • 49.Yousseif A, Emmanuel J, Karra E, Millet Q, Elkalaawy M, Jenkinson AD, et al. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes Surg. 2014;24(2):241–252. doi: 10.1007/s11695-013-1066-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Bose M, Teixeira J, Olivan B, Bawa B, Arias S, Machineni S, et al. Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery. J Diabetes. 2010;2(1):47–55. doi: 10.1111/j.1753-0407.2009.00064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Gelisgen R, Zengin K, Kocael A, Baysal B, Kocael P, Erman H, et al. Effects of laparoscopic gastric band applications on plasma and fundic acylated ghrelin levels in morbidly obese patients. Obes Surg. 2012;22(2):299–305. doi: 10.1007/s11695-011-0498-7. [DOI] [PubMed] [Google Scholar]
  • 52.Gueugnon C, Mougin F, Nguyen NU, Bouhaddi M, Nicolet-Guénat M, Dumoulin G. Ghrelin and PYY levels in adolescents with severe obesity: effects of weight loss induced by long-term exercise training and modified food habits. Eur J Appl Physiol. 2012;112(5):1797–1805. doi: 10.1007/s00421-011-2154-2. [DOI] [PubMed] [Google Scholar]
  • 53.Hill BR, De Souza MJ, Wagstaff DA, Williams NI. The impact of weight loss on the 24-h profile of circulating peptide YY and its association with 24-h ghrelin in normal weight premenopausal women. Peptides. 2013;49:81–90. doi: 10.1016/j.peptides.2013.08.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Isbell JM, Tamboli RA, Hansen EN, Saliba J, Dunn JP, Phillips SE, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33(7):1438–1442. doi: 10.2337/dc09-2107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Plum L, Ahmed L, Febres G, Bessler M, Inabnet W, Kunreuther E, et al. Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss. Obesity (Silver Spring) 2011;19(11):2149–2157. doi: 10.1038/oby.2011.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Rodieux F, Giusti V, D'Alessio DA, Suter M, Tappy L. Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release. Obesity (Silver Spring) 2008;16(2):298–305. doi: 10.1038/oby.2007.83. [DOI] [PubMed] [Google Scholar]
  • 57.Scholtz S, Miras AD, Chhina N, Prechtl CG, Sleeth ML, Daud NM, et al. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut. 2014;63(6):891–902. doi: 10.1136/gutjnl-2013-305008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • *58.Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597–1604. doi: 10.1056/NEJMoa1105816. [DOI] [PubMed] [Google Scholar]
  • 59.Libman IM, Barinas-Mitchell E, Bartucci A, Robertson R, Arslanian S. Reproducibility of the oral glucose tolerance test in overweight children. J Clin Endocrinol Metab. 2008;93(11):4231–4237. doi: 10.1210/jc.2008-0801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Rubino F, Zizzari P, Tomasetto C, Bluet-Pajot MT, Forgione A, Vix M, et al. The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat. Endocrinology. 2005;146(4):1745–1751. doi: 10.1210/en.2004-1181. [DOI] [PubMed] [Google Scholar]
  • 61.Lee WJ, Chen CY, Chong K, Lee YC, Chen SC, Lee SD. Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy. Surg Obes Relat Dis. 2011;7(6):683–690. doi: 10.1016/j.soard.2011.07.009. [DOI] [PubMed] [Google Scholar]
  • 62.Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88(4):1594–1602. doi: 10.1210/jc.2002-021309. [DOI] [PubMed] [Google Scholar]
  • 63.Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83. doi: 10.1006/bbrc.1999.0255. [DOI] [PubMed] [Google Scholar]
  • 64.Acharya SD, Brooks MM, Evans RW, Linkov F, Burke LE. Weight loss is more important than the diet type in improving adiponectin levels among overweight/obese adults. J Am Coll Nutr. 2013;32(4):264–271. doi: 10.1080/07315724.2013.816607. [DOI] [PubMed] [Google Scholar]
  • 65.Engl J, Bobbert T, Ciardi C, Laimer M, Tatarczyk T, Kaser S, et al. Effects of pronounced weight loss on adiponectin oligomer composition and metabolic parameters. Obesity (Silver Spring) 2007;15(5):1172–1178. doi: 10.1038/oby.2007.627. [DOI] [PubMed] [Google Scholar]
  • 66.Golubović MV, Dimić D, Antić S, Radenković S, Djindjić B, Jovanović M. Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction. Vojnosanit Pregl. 2013;70(3):284–291. doi: 10.2298/vsp1303284v. [DOI] [PubMed] [Google Scholar]
  • 67.Ruth MR, Port AM, Shah M, Bourland AC, Istfan NW, Nelson KP, et al. Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. Metabolism. 2013;62(12):1779–1787. doi: 10.1016/j.metabol.2013.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Bradley D, Conte C, Mittendorfer B, Eagon JC, Varela JE, Fabbrini E, et al. Gastric bypass and banding equally improve insulin sensitivity and β cell function. J Clin Invest. 2012;122(12):4667–4674. doi: 10.1172/JCI64895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Couce ME, Cottam D, Esplen J, Schauer P, Burguera B. Is ghrelin the culprit for weight loss after gastric bypass surgery? A negative answer. Obes Surg. 2006;16(7):870–878. doi: 10.1381/096089206777822151. [DOI] [PubMed] [Google Scholar]
  • 70.Coughlin CC, Finck BN, Eagon JC, Halpin VJ, Magkos F, Mohammed BS, et al. Effect of marked weight loss on adiponectin gene expression and plasma concentrations. Obesity (Silver Spring) 2007;15(3):640–645. doi: 10.1038/oby.2007.556. [DOI] [PubMed] [Google Scholar]
  • 71.de Carvalho CP, Marin DM, de Souza AL, Pareja JC, Chaim EA, de Barros Mazon S, et al. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg. 2009;19(3):313–320. doi: 10.1007/s11695-008-9678-5. [DOI] [PubMed] [Google Scholar]
  • 72.García de la Torre N, Rubio MA, Bordiú E, Cabrerizo L, Aparicio E, Hernández C, et al. Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab. 2008;93(11):4276–4281. doi: 10.1210/jc.2007-1370. [DOI] [PubMed] [Google Scholar]
  • 73.Garrido-Sanchez L, Murri M, Rivas-Becerra J, Ocaña-Wilhelmi L, Cohen RV, Garcia-Fuentes E, et al. Bypass of the duodenum improves insulin resistance much more rapidly than sleeve gastrectomy. Surg Obes Relat Dis. 2012;8(2):145–150. doi: 10.1016/j.soard.2011.03.010. [DOI] [PubMed] [Google Scholar]
  • 74.Holdstock C, Engström BE, Ohrvall M, Lind L, Sundbom M, Karlsson FA. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab. 2003;88(7):3177–3183. doi: 10.1210/jc.2002-021734. [DOI] [PubMed] [Google Scholar]
  • 75.Swarbrick MM, Austrheim-Smith IT, Stanhope KL, Van Loan MD, Ali MR, Wolfe BM, et al. Circulating concentrations of high-molecular-weight adiponectin are increased following Roux-en-Y gastric bypass surgery. Diabetologia. 2006;49(11):2552–2558. doi: 10.1007/s00125-006-0452-8. [DOI] [PubMed] [Google Scholar]
  • 76.Vendrell J, Broch M, Vilarrasa N, Molina A, Gómez JM, Gutiérrez C, et al. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res. 2004;12(6):962–971. doi: 10.1038/oby.2004.118. [DOI] [PubMed] [Google Scholar]
  • 77.Woelnerhanssen B, Peterli R, Steinert RE, Peters T, Borbély Y, Beglinger C. Effects of postbariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy--a prospective randomized trial. Surg Obes Relat Dis. 2011;7(5):561–568. doi: 10.1016/j.soard.2011.01.044. [DOI] [PubMed] [Google Scholar]
  • 78.Chen J, Spagnoli A, Torquati A. Omental gene expression of adiponectin correlates with degree of insulin sensitivity before and after gastric bypass surgery. Obes Surg. 2012;22(3):472–477. doi: 10.1007/s11695-011-0568-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Geloneze B, Pereira JA, Pareja JC, Lima MM, Lazarin MA, Souza IC, et al. Overcoming metabolic syndrome in severe obesity: adiponectin as a marker of insulin sensitivity and HDL-cholesterol improvements after gastric bypass. Arq Bras Endocrinol Metabol. 2009;53(2):293–300. doi: 10.1590/s0004-27302009000200022. [DOI] [PubMed] [Google Scholar]
  • 80.Illán-Gómez F, Gonzálvez-Ortega M, Orea-Soler I, Alcaraz-Tafalla MS, Aragón-Alonso A, Pascual-Díaz M, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg. 2012;22(6):950–955. doi: 10.1007/s11695-012-0643-y. [DOI] [PubMed] [Google Scholar]
  • 81.Navaneethan SD, Kelly KR, Sabbagh F, Schauer PR, Kirwan JP, Kashyap SR. Urinary albumin excretion, HMW adiponectin, and insulin sensitivity in type 2 diabetic patients undergoing bariatric surgery. Obes Surg. 2010;20(3):308–315. doi: 10.1007/s11695-009-0026-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Savu MK, Phillips SA, Oh DK, Park K, Gerlan C, Ciaraldi TP, et al. Response of adiponectin and its receptors to changes in metabolic state after gastric bypass surgery: dissociation between adipose tissue expression and circulating levels. Surg Obes Relat Dis. 2009;5(2):172–180. doi: 10.1016/j.soard.2008.08.013. [DOI] [PubMed] [Google Scholar]
  • 83.Shrestha C, He H, Liu Y, Zhu S, Xiong J, Mo Z. Changes in Adipokines following Laparoscopic Roux-en-Y Gastric Bypass Surgery in Chinese Individuals with Type 2 Diabetes Mellitus and BMI of 22-30 kg·m(-2.) Int J Endocrinol. 2013;2013:240971. doi: 10.1155/2013/240971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Umeda LM, Pereira AZ, Carneiro G, Arasaki CH, Zanella MT. Postprandial adiponectin levels are associated with improvements in postprandial triglycerides after Roux-en-Y gastric bypass in type 2 diabetic patients. Metab Syndr Relat Disord. 2013;11(5):343–348. doi: 10.1089/met.2012.0042. [DOI] [PubMed] [Google Scholar]
  • 85.Banasik JL, Walker MK, Randall JM, Netjes RB, Foutz MS. Low-calorie diet induced weight loss may alter regulatory hormones and contribute to rebound visceral adiposity in obese persons with a family history of type-2 diabetes. J Am Assoc Nurse Pract. 2013;25(8):440–448. doi: 10.1111/j.1745-7599.2012.00808.x. [DOI] [PubMed] [Google Scholar]
  • *86.Geloneze B, Geloneze SR, Chaim E, Hirsch FF, Felici AC, Lambert G, et al. Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study. Ann Surg. 2012;256(1):72–78. doi: 10.1097/SLA.0b013e3182592c62. [DOI] [PubMed] [Google Scholar]
  • 87.Evans S, Pamuklar Z, Rosko J, Mahaney P, Jiang N, Park C, et al. Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction. Surg Endosc. 2012;26(4):1086–1094. doi: 10.1007/s00464-011-2004-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Svendsen PF, Jensen FK, Holst JJ, Haugaard SB, Nilas L, Madsbad S. The effect of a very low calorie diet on insulin sensitivity, beta cell function, insulin clearance, incretin hormone secretion, androgen levels and body composition in obese young women. Scand J Clin Lab Invest. 2012;72(5):410–419. doi: 10.3109/00365513.2012.691542. [DOI] [PubMed] [Google Scholar]
  • 89.Valderas JP, Irribarra V, Rubio L, Boza C, Escalona M, Liberona Y, et al. Effects of sleeve gastrectomy and medical treatment for obesity on glucagon-like peptide 1 levels and glucose homeostasis in non-diabetic subjects. Obes Surg. 2011;21(7):902–909. doi: 10.1007/s11695-011-0375-4. [DOI] [PubMed] [Google Scholar]
  • 90.Yip S, Signal M, Smith G, Beban G, Booth M, Babor R, et al. Lower glycemic fluctuations early after bariatric surgery partially explained by caloric restriction. Obes Surg. 2014;24(1):62–70. doi: 10.1007/s11695-013-1043-7. [DOI] [PubMed] [Google Scholar]
  • 91.Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis. 2007;3(6):597–601. doi: 10.1016/j.soard.2007.08.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Reinehr T, Roth CL, Schernthaner GH, Kopp HP, Kriwanek S, Schernthaner G. Peptide YY and glucagon-like peptide-1 in morbidly obese patients before and after surgically induced weight loss. Obes Surg. 2007;17(12):1571–1577. doi: 10.1007/s11695-007-9323-8. [DOI] [PubMed] [Google Scholar]
  • 93.Usinger L, Hansen KB, Kristiansen VB, Larsen S, Holst JJ, Knop FK. Gastric emptying of orally administered glucose solutions and incretin hormone responses are unaffected by laparoscopic adjustable gastric banding. Obes Surg. 2011;21(5):625–632. doi: 10.1007/s11695-011-0362-9. [DOI] [PubMed] [Google Scholar]
  • 94.Romero F, Nicolau J, Flores L, Casamitjana R, Ibarzabal A, Lacy A, et al. Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects. Surg Endosc. 2012;26(8):2231–2239. doi: 10.1007/s00464-012-2166-y. [DOI] [PubMed] [Google Scholar]
  • *95.Steinert RE, Peterli R, Keller S, Meyer-Gerspach AC, Drewe J, Peters T, et al. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity (Silver Spring) 2013;21(12):E660–E668. doi: 10.1002/oby.20522. [DOI] [PubMed] [Google Scholar]
  • 96.Werling M, Vincent RP, Cross GF, Marschall HU, Fändriks L, Lönroth H, et al. Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery. Scand J Gastroenterol. 2013;48(11):1257–1264. doi: 10.3109/00365521.2013.833647. [DOI] [PubMed] [Google Scholar]
  • 97.Basso N, Capoccia D, Rizzello M, Abbatini F, Mariani P, Maglio C, et al. First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis. Surg Endosc. 2011;25(11):3540–3550. doi: 10.1007/s00464-011-1755-5. [DOI] [PubMed] [Google Scholar]
  • 98.Smushkin G, Sathananthan M, Piccinini F, Dalla Man C, Law JH, Cobelli C, et al. The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes. 2013;62(4):1094–1101. doi: 10.2337/db12-0923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Garg SK, Ritchie PJ, Moser EG, Snell-Bergeon JK, Freson BJ, Hazenfield RM. Effects of colesevelam on LDL-C, A1c and GLP-1 levels in patients with type 1 diabetes: a pilot randomized doubleblind trial. Diabetes Obes Metab. 2011;13(2):137–143. doi: 10.1111/j.1463-1326.2010.01320.x. [DOI] [PubMed] [Google Scholar]
  • 100.Beysen C, Murphy EJ, Deines K, Chan M, Tsang E, Glass A, et al. Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study. Diabetologia. 2012;55(2):432–442. doi: 10.1007/s00125-011-2382-3. [DOI] [PubMed] [Google Scholar]
  • 101.Chen L, McNulty J, Anderson D, Liu Y, Nystrom C, Bullard S, et al. Cholestyramine reverses hyperglycemia and enhances glucose-stimulated glucagon-like peptide 1 release in Zucker diabetic fatty rats. J Pharmacol Exp Ther. 2010;334(1):164–170. doi: 10.1124/jpet.110.166892. [DOI] [PubMed] [Google Scholar]
  • 102.Shang Q, Saumoy M, Holst JJ, Salen G, Xu G. Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1. Am J Physiol Gastrointest Liver Physiol. 2010;298(3):G419–G424. doi: 10.1152/ajpgi.00362.2009. [DOI] [PubMed] [Google Scholar]
  • 103.Potthoff MJ, Potts A, He T, Duarte JA, Taussig R, Mangelsdorf DJ, et al. Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice. Am J Physiol Gastrointest Liver Physiol. 2013;304(4):G371–G380. doi: 10.1152/ajpgi.00400.2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104.Marina AL, Utzschneider KM, Wright LA, Montgomery BK, Marcovina SM, Kahn SE. Colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and β-cell function. Diabetes Care. 2012;35(5):1119–1125. doi: 10.2337/dc11-2050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 105.Fleishaker JC, Rossi SS, Smith RB, Welshman IR, Daei F, Angellotti MA, et al. The effect of colestipol dose on postprandial serum bile acid concentration: assessment by an enzymic bioluminescence procedure. Aliment Pharmacol Ther. 1990;4(6):623–633. doi: 10.1111/j.1365-2036.1990.tb00510.x. [DOI] [PubMed] [Google Scholar]
  • 106.Rossi SS, Wayne ML, Smith RB, Wright CE, Andreadis NA, Hofmann AF. Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis. Aliment Pharmacol Ther. 1989;3(1):41–46. doi: 10.1111/j.1365-2036.1989.tb00189.x. [DOI] [PubMed] [Google Scholar]
  • 107.Kuiper EM, van Erpecum KJ, Beuers U, Hansen BE, Thio HB, de Man RA, et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52(4):1334–1340. doi: 10.1002/hep.23821. [DOI] [PubMed] [Google Scholar]
  • *108.Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–177. doi: 10.1016/j.cmet.2009.08.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 109.Ortega FJ, Moreno-Navarrete JM, Sabater M, Ricart W, Frühbeck G, Fernández-Real JM. Circulating glucagon is associated with inflammatory mediators in metabolically compromised subjects. Eur J Endocrinol. 2011;165(4):639–645. doi: 10.1530/EJE-11-0384. [DOI] [PubMed] [Google Scholar]
  • 110.Laferrère B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93(7):2479–2485. doi: 10.1210/jc.2007-2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 111.Villareal DT, Banks MR, Patterson BW, Polonsky KS, Klein S. Weight loss therapy improves pancreatic endocrine function in obese older adults. Obesity (Silver Spring) 2008;16(6):1349–1354. doi: 10.1038/oby.2008.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 112.Swarbrick MM, Stanhope KL, Austrheim-Smith IT, Van Loan MD, Ali MR, Wolfe BM, et al. Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery. Diabetologia. 2008;51(10):1901–1911. doi: 10.1007/s00125-008-1118-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Bone HG, Lindsay R, McClung MR, Perez AT, Raanan MG, Spanheimer RG. Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013;98(12):4691–4701. doi: 10.1210/jc.2012-4096. [DOI] [PubMed] [Google Scholar]
  • 114.Dixon AF, le Roux CW, Ghatei MA, Bloom SR, McGee TL, Dixon JB. Pancreatic polypeptide meal response may predict gastric band-induced weight loss. Obes Surg. 2011;21(12):1906–1913. doi: 10.1007/s11695-011-0469-z. [DOI] [PubMed] [Google Scholar]
  • 115.Papamargaritis D, le Roux CW, Sioka E, Koukoulis G, Tzovaras G, Zacharoulis D. Changes in gut hormone profile and glucose homeostasis after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis. 2013;9(2):192–201. doi: 10.1016/j.soard.2012.08.007. [DOI] [PubMed] [Google Scholar]
  • 116.Sun D, Wang K, Yan Z, Zhang G, Liu S, Liu F, et al. Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats. Obes Surg. 2013;23(11):1734–1742. doi: 10.1007/s11695-013-0985-0. [DOI] [PubMed] [Google Scholar]
  • 117.Rigamonti AE, Resnik M, Compri E, Agosti F, De Col A, Monteleone P, et al. The cholestyramine-induced decrease of PYY postprandial response is negatively correlated with fat mass in obese women. Horm Metab Res. 2011;43(8):569–573. doi: 10.1055/s-0031-1280783. [DOI] [PubMed] [Google Scholar]
  • 118.Glicksman C, Pournaras DJ, Wright M, Roberts R, Mahon D, Welbourn R, et al. Postprandial plasma bile acid responses in normal weight and obese subjects. Ann Clin Biochem. 2010;47(Pt 5):482–484. doi: 10.1258/acb.2010.010040. [DOI] [PubMed] [Google Scholar]
  • 119.Halmy L, Fehér T, Steczek K, Farkas A. High serum bile acid level in obesity: its decrease during and after total fasting. Acta Med Hung. 1986;43(1):55–58. [PubMed] [Google Scholar]
  • 120.Mok HY, von Bergmann K, Crouse JR, Grundy SM. Bilary lipid metabolism in obesity. Effects of bile acid feeding before and during weight reduction. Gastroenterology. 1979;76(3):556–567. [PubMed] [Google Scholar]
  • 121.Trouillot TE, Pace DG, McKinley C, Cockey L, Zhi J, Haeussler J, et al. Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss. Am J Gastroenterol. 2001;96(6):1888–1894. doi: 10.1111/j.1572-0241.2001.03783.x. [DOI] [PubMed] [Google Scholar]
  • 122.Nakatani H, Kasama K, Oshiro T, Watanabe M, Hirose H, Itoh H. Serum bile acid along with plasma incretins and serum high-molecular weight adiponectin levels are increased after bariatric surgery. Metabolism. 2009;58(10):1400–1407. doi: 10.1016/j.metabol.2009.05.006. [DOI] [PubMed] [Google Scholar]
  • 123.Kohli R, Bradley D, Setchell KD, Eagon JC, Abumrad N, Klein S. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab. 2013;98(4):E708–E712. doi: 10.1210/jc.2012-3736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Ahmad NN, Pfalzer A, Kaplan LM. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes (Lond) 2013;37(12):1553–1559. doi: 10.1038/ijo.2013.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 125.Ashrafian H, Li JV, Spagou K, Harling L, Masson P, Darzi A, et al. Bariatric surgery modulates circulating and cardiac metabolites. J Proteome Res. 2014;13(2):570–580. doi: 10.1021/pr400748f. [DOI] [PubMed] [Google Scholar]
  • 126.Gerhard GS, Styer AM, Wood GC, Roesch SL, Petrick AT, Gabrielsen J, et al. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care. 2013;36(7):1859–1864. doi: 10.2337/dc12-2255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 127.Jansen PL, van Werven J, Aarts E, Berends F, Janssen I, Stoker J, et al. Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery. Dig Dis. 2011;29(1):48–51. doi: 10.1159/000324128. [DOI] [PubMed] [Google Scholar]
  • 128.Patti ME, Houten SM, Bianco AC, Bernier R, Larsen PR, Holst JJ, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring) 2009;17(9):1671–1677. doi: 10.1038/oby.2009.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129.Simonen M, Dali-Youcef N, Kaminska D, Venesmaa S, Käkelä P, Pääkkönen M, et al. Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass. Obes Surg. 2012;22(9):1473–1480. doi: 10.1007/s11695-012-0673-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 130.Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2014;11(1):55–67. doi: 10.1038/nrgastro.2013.151. [DOI] [PubMed] [Google Scholar]
  • 131.Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband-Zadeh J, Mahon D, et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012;153(8):3613–3619. doi: 10.1210/en.2011-2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Lundåsen T, Gälman C, Angelin B, Rudling M. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med. 2006;260(6):530–536. doi: 10.1111/j.1365-2796.2006.01731.x. [DOI] [PubMed] [Google Scholar]
  • *133.David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–563. doi: 10.1038/nature12820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 134.Sayin SI, Wahlström A, Felin J, Jäntti S, Marschall HU, Bamberg K, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17(2):225–235. doi: 10.1016/j.cmet.2013.01.003. [DOI] [PubMed] [Google Scholar]
  • 135.Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837–848. doi: 10.1016/j.cell.2006.02.017. [DOI] [PubMed] [Google Scholar]
  • 136.Armougom F, Henry M, Vialettes B, Raccah D, Raoult D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One. 2009;4(9):e7125. doi: 10.1371/journal.pone.0007125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 137.Balamurugan R, George G, Kabeerdoss J, Hepsiba J, Chandragunasekaran AM, Ramakrishna BS. Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children. Br J Nutr. 2010;103(3):335–338. doi: 10.1017/S0007114509992182. [DOI] [PubMed] [Google Scholar]
  • *138.Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59(12):3049–3057. doi: 10.2337/db10-0253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 139.Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond) 2008;32(11):1720–1724. doi: 10.1038/ijo.2008.155. [DOI] [PubMed] [Google Scholar]
  • 140.Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri JM, Garagorri M, et al. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond) 2009;33(7):758–767. doi: 10.1038/ijo.2008.260. [DOI] [PubMed] [Google Scholar]
  • 141.Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180. doi: 10.1038/nature09944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 142.Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106(7):2365–2370. doi: 10.1073/pnas.0812600106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 143.Li JV, Reshat R, Wu Q, Ashrafian H, Bueter M, le Roux CW, et al. Experimental bariatric surgery in rats generates a cytotoxic chemical environment in the gut contents. Front Microbiol. 2011;2:183. doi: 10.3389/fmicb.2011.00183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 144.Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13(6):514–522. doi: 10.1038/tpj.2012.43. [DOI] [PubMed] [Google Scholar]
  • 145.Osto M, Abegg K, Bueter M, le Roux CW, Cani PD, Lutz TA. Roux-en-Y gastric bypass surgery in rats alters gut microbiota profile along the intestine. Physiol Behav. 2013;119:92–96. doi: 10.1016/j.physbeh.2013.06.008. [DOI] [PubMed] [Google Scholar]
  • 146.Vrieze A, Out C, Fuentes S, Jonker L, Reuling I, Kootte RS, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824–831. doi: 10.1016/j.jhep.2013.11.034. [DOI] [PubMed] [Google Scholar]
  • 147.Wu T, Zhang Z, Liu B, Hou D, Liang Y, Zhang J, et al. Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study. BMC Genomics. 2013;14:669. doi: 10.1186/1471-2164-14-669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 148.Woodard GA, Encarnacion B, Downey JR, Peraza J, Chong K, Hernandez-Boussard T, et al. Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg. 2009;13(7):1198–1204. doi: 10.1007/s11605-009-0891-x. [DOI] [PubMed] [Google Scholar]

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