modif cell nitestinale ap chir baria 2017 pharma.pdf
32 Endocrine and metabolic diseases
after RYGB, associated with an increase in TER. These
results suggest a decreased paracellular permeability after
RYGB that could eventually contribute to decreased LPS
translocation. However, this study only addressed the
adaptation of the RYGB-remodelled jejunum where only
few bacteria are present and changes in epithelial permeability of the distal parts of the small intestine and
colon remain to be explored. Another study, using a
mouse model of sleeve gastrectomy, reported a decrease
in jejunal permeability after 4weeks and an increase in
colonic permeability associated with an increase in LPS
translocation in the plasma . This observation contradicts a human study, which reported that LPS levels are
diminished after sleeve surgeries . However, in the
murine study, animals were maintained on a high fat diet
after surgery and changes in nutrient composition, in
particular fat content, may play a role in the ameliorated
intestinal barrier function.
In addition, changes in gut microbiota after bariatric
surgery in human or murine models and their relation
to improved metabolic state have been largely illustrated
[39–42,43 ]. Faecal transplantation, which significantly
alters gut microbiota composition and associated phenotype, represents one of the most promising tools for GI
and metabolic disorders .
Alternatively, the bacteria specie Akkermansia muciniphila
by itself can improve obesity associated metabolic conditions . Recently, a specific A. muciniphila product
(Amuc_1100) has been shown to mimic part of the effects
of the living organism and could thus be a therapeutic tool
in the management of the obesity [50 ].
Could bariatric surgery help to design new therapeutic
targets to improve intestinal permeability? GLP-2, an
enterohormone co-secreted with GLP-1, has been
reported to be increased in patients after bariatric surgery
[9,51] and was shown in mice to improve barrier function
and reduce metabolic endotoxemia . The pharmacological GLP-2 analogue Teduglutide is already used in
patients suffering from short bowel syndrome in order to
increase intestinal growth and to improve intestinal function . The use of teduglutide as a treatment to prevent
endotoxemia in obese patients merits further
The three main functions of the GI tract — nutrient
absorption, endocrine secretion and barrier integrity —
are modified by bariatric surgery. Each of these modifications seem to contribute to the beneficial effects of the
procedures. Recent research and drug development programmes offer the potential of new opportunities to
mimic some of the effects of surgery, but no single drug
is able to equal the surgical intervention. Although the
most promising recent development is a monomeric
Current Opinion in Pharmacology 2017, 37:29–34
GLP1/GIP/glucagon triagonist [54 ,55]. Whether using
a combination/cocktail of drugs will be safe, appropriate
for long-term use and less constraining than the surgery
itself remains to be evaluated.
This work was supported by Inserm, University Paris
Diderot. LRP received funding from the Fondation pour
la Recherche Me´dicale, JBC received funding from Afero
and the Prix Claude Roze´, MLG received funding from
Socie´te´ Francophone du Diabe`te, SFNEP and Institut
Conflict of interest statement
We thanks all Bado’s team members and especially A. Bado for advice and
constant support. We are grateful to Dr Lionel Arnaud for drawing Figure 1,
and to Nicholas Nguyen for English editing.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
of special interest
of outstanding interest
Mahawar KK, Sharples AJ: Contribution of malabsorption to
weight loss after Roux-en-Y gastric bypass: a systematic
review. Obes Surg 2017 http://dx.doi.org/10.1007/s11695-0172762-y.
Batterham RL, Cummings DE: Mechanisms of diabetes
improvement following bariatric/metabolic surgery. Diabetes
Care 2016, 39:893-901.
Sweeney TE, Morton JM: Metabolic surgery: action via
hormonal milieu changes, changes in bile acids or gut
microbiota? A summary of the literature. Best Pract Res Clin
Gastroenterol 2014, 28:727-740.
Meek CL, Lewis HB, Reimann F, Gribble FM, Park AJ: The effect
of bariatric surgery on gastrointestinal and pancreatic peptide
hormones. Peptides 2016, 77:28-37.
Salehi M, D’Alessio DA: Effects of glucagon like peptide-1 to
mediate glycemic effects of weight loss surgery. Rev Endocr
Metab Disord 2014, 15:171-179.
Cummings DE, Overduin J, Foster-Schubert KE: Gastric bypass
for obesity: mechanisms of weight loss and diabetes
resolution. J Clin Endocrinol Metab 2004, 89:2608-2615.
Chambers AP, Smith EP, Begg DP, Grayson BE, Sisley S, Greer T,
Sorrell J, Lemmen L, LaSance K, Woods SC et al.: Regulation of
gastric emptying rate and its role in nutrient-induced GLP-1
secretion in rats after vertical sleeve gastrectomy. Am J Physiol
Endocrinol Metab 2014, 306:E424-E432.
Nguyen NQ, Debreceni TL, Bambrick JE, Chia B, Deane AM,
Wittert G, Rayner CK, Horowitz M, Young RL: Upregulation of
intestinal glucose transporters after Roux-en-Y gastric
bypass to prevent carbohydrate malabsorption. Obesity 2014,
le Roux CWM, Borg CF, Wallis KM, Vincent RP, Bueter M,
Goodlad R, Ghatei MA, Patel AF, Bloom SRF, Aylwin SJBF: Gut
hypertrophy after gastric bypass is associated with increased
glucagon-like peptide 2 and intestinal crypt cell proliferation.
Ann Surg 2010, 252:50-56.
10. Taqi E, Wallace LE, de Heuvel E, Chelikani PK, Zheng H,
Berthoud H-R, Holst JJ, Sigalet DL: The influence of nutrients,
biliary-pancreatic secretions, and systemic trophic hormones