scholarly journals Mechanisms controlling hormone secretion in human gut and its relevance to metabolism

2020 ◽  
Vol 244 (1) ◽  
pp. R1-R15 ◽  
Author(s):  
Alyce M Martin ◽  
Emily W Sun ◽  
Damien J Keating
Keyword(s):  
Hormone Secretion ◽  
Enteroendocrine Cells ◽  
Microbial Metabolites ◽  
Human Gut ◽  
Glucose Lowering ◽  
Endocrine Organ ◽  
Metabolic Functions ◽  
Gut Epithelium ◽  
Gut Hormone ◽  
Regulation Of Metabolism

The homoeostatic regulation of metabolism is highly complex and involves multiple inputs from both the nervous and endocrine systems. The gut is the largest endocrine organ in our body and synthesises and secretes over 20 different hormones from enteroendocrine cells that are dispersed throughout the gut epithelium. These hormones include GLP-1, PYY, GIP, serotonin, and CCK, each of which play pivotal roles in maintaining energy balance and glucose homeostasis. Some are now the basis of several clinically used glucose-lowering and weight loss therapies. The environment in which these enteroendocrine cells exist is also complex, as they are exposed to numerous physiological inputs including ingested nutrients, circulating factors and metabolites produced from neighbouring gut microbiome. In this review, we examine the diverse means by which gut-derived hormones carry out their metabolic functions through their interactions with different metabolically important organs including the liver, pancreas, adipose tissue and brain. Furthermore, we discuss how nutrients and microbial metabolites affect gut hormone secretion and the mechanisms underlying these interactions.

scholarly journals Human intestinal enteroids with inducible neurogenin-3 expression as a novel model of gut hormone secretion

2019 ◽  
Author(s):  
Alexandra L. Chang-Graham ◽  
Heather A. Danhof ◽  
Melinda A. Engevik ◽  
Catherine Tomaro-Duchesneau ◽  
Umesh C. Karandikar ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Cell Types ◽  
Inducible Expression ◽  
Enteroendocrine Cells ◽  
Neurogenin 3 ◽  
Rotavirus Infection ◽  
Functional Studies ◽  
Gut Hormone ◽  
The Impact

AbstractBackgroundEnteroendocrine cells (EECs) are specialized epithelial cells that produce molecules vital for intestinal homeostasis, but due to their limited numbers, in-depth functional studies have remained challenging. Human intestinal enteroids (HIEs) that are derived from intestinal crypt stem cells are a biologically relevantin vitromodel of the intestinal epithelium. HIEs contain all intestinal epithelial cell types; however, like the intestine, HIEs spontaneously produce few EECs, which limits their study.MethodsTo increase the number of EECs in HIEs, we used lentivirus transduction to stably engineer jejunal HIEs with doxycycline-inducible expression of neurogenin-3 (NGN3), a transcription factor that drives EEC differentiation (tetNGN3-HIEs). We examined the impact ofNGN3induction on EECs by quantifying the increase in the enterochromaffin cells and other EEC subtypes. We functionally assessed secretion of serotonin and EEC hormones in response to norepinephrine and rotavirus infection.ResultsTreating tetNGN3-HIEs with doxycycline induced a dose-dependent increase of chromogranin A (ChgA)-positive and serotonin-positive cells, demonstrating increased enterochromaffin cell differentiation. Despite increased ChgA-positive cells, other differentiated cell types of the epithelium remained largely unchanged by gene expression and immunostaining. RNA sequencing of doxycycline-induced tetNGN3- HIEs identified increased expression of key hormones and enzymes associated with several other EEC subtypes. Doxycycline-induced tetNGN3-HIEs secreted serotonin, monocyte chemoattractant protein-1, glucose-dependent insulinotropic peptide, peptide YY, and ghrelin in response to norepinephrine and rotavirus infection, further supporting the presence of multiple EEC types.ConclusionsWe have combined HIEs and inducible-NGN3expression to establish a flexiblein vitromodel system for functional studies of EECs in enteroids and advance the molecular and physiological investigation of EECs.SynopsisEnteroendocrine cells have low abundance but exert widespread effects on gastrointestinal physiology. We engineered human intestinal enteroids with inducible expression of neurogenin-3, resulting in increased enteroendocrine cells and facilitating investigations of host responses to the dynamic intestinal environment.

scholarly journals Monitoring the Diversity and Metabolic Shift of Gut Microbes during Green Tea Feeding in an In Vitro Human Colonic Model

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5101
Author(s):  
Mengyang Xu ◽  
Kundi Yang ◽  
Jiangjiang Zhu
Keyword(s):  
Human Health ◽  
Green Tea ◽  
Microbial Population ◽  
Green Tea Extract ◽  
Microbial Metabolites ◽  
Human Gut ◽  
Microbial Composition ◽  
Metabolic Functions ◽  
Tea Extract

The human gut microbiome plays an important role in human health, and many factors such as environment, host genetics, age, and diet have been found to influence the microbial composition. Tea, as one of the widely consumed beverages, has been known for centuries to have antioxidant, anti-inflammatory, and anticancer effects. To investigate the impact of green tea polyphenol on the diversity and metabolic functions of human gut microbes, we applied an in vitro human colonic model (HCM) in this study to mimic a short-term green tea ingestion event and investigate its related changes to gut microbial composition and their metabolic functions. The pH, temperature, anaerobic environment, feeding nutrient, and time point in each compartment of the HCM were tightly controlled to simulate the intestinal system, and pooled human fecal samples of two healthy volunteers were used for the colon microbiota inoculation within the colonic model. By adding green tea extract (GTE) to the growth medium, the detailed impacts of GTE polyphenol on gut microbial population/diversity, gut microbial metabolites, metabolic pathways, and their associations were investigated via 16 S ribosomal DNA sequencing and liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analyses. Our data indicated that the treatment of green tea extract applied to gut microbiota can induce a significant decrease in the abundance of Firmicutes and a slight decrease in the abundance of Bacteroidetes, and these changes result in a decreased Firmicutes/Bacteroidetes ratio, which can be an effective indicator for successful GTE intervention, which may generate beneficial health effect to human. Meanwhile, the relative abundances of many detected bacteria genera among three HCM vessels changed through the GTE intervention. The overall effects of GTE on gut microbial beta-diversity were observed by multivariate statistical analyses, and the differences in metabolic profiles from different GTE treatment stages were detected. Moreover, we identified several associations between microbial population and microbial metabolites, which may assist us in establishing new hypotheses for future related studies. In summary, our study suggested that the microbial compositional changes induced by GTE also changed their metabolic functions, and consequentially, may change the host metabolism and impact human health.

scholarly journals Targeting the Gut in Obesity: Signals from the Inner Surface

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 39
Author(s):  
Natalia Petersen ◽  
Thomas U. Greiner ◽  
Lola Torz ◽  
Angie Bookout ◽  
Marina Kjærgaard Gerstenberg ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Gut Hormones ◽  
Energy Balance Equation ◽  
Enteroendocrine Cells ◽  
Therapeutic Interventions ◽  
Microbial Metabolites ◽  
Dipeptidyl Peptidase 4 ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Obesity is caused by prolonged energy surplus. Current anti-obesity medications are mostly centralized around the energy input part of the energy balance equation by increasing satiety and reducing appetite. Our gastrointestinal tract is a key organ for regulation of food intake and supplies a tremendous number of circulating signals that modulate the activity of appetite-regulating areas of the brain by either direct interaction or through the vagus nerve. Intestinally derived messengers are manifold and include absorbed nutrients, microbial metabolites, gut hormones and other enterokines, collectively comprising a fine-tuned signalling system to the brain. After a meal, nutrients directly interact with appetite-inhibiting areas of the brain and induce satiety. However, overall feeding behaviour also depends on secretion of gut hormones produced by highly specialized and sensitive enteroendocrine cells. Moreover, circulating microbial metabolites and their interactions with enteroendocrine cells further contribute to the regulation of feeding patterns. Current therapies exploiting the appetite-regulating properties of the gut are based on chemically modified versions of the gut hormone, glucagon-like peptide-1 (GLP-1) or on inhibitors of the primary GLP-1 inactivating enzyme, dipeptidyl peptidase-4 (DPP-4). The effectiveness of these approaches shows that that the gut is a promising target for therapeutic interventions to achieve significant weigh loss. We believe that increasing understanding of the functionality of the intestinal epithelium and new delivery systems will help develop selective and safe gut-based therapeutic strategies for improved obesity treatment in the future. Here, we provide an overview of the major homeostatic appetite-regulating signals generated by the intestinal epithelial cells and how these signals may be harnessed to treat obesity by pharmacological means.

scholarly journals Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 883
Author(s):  
Van B. Lu ◽  
Fiona M. Gribble ◽  
Frank Reimann
Keyword(s):  
Gastrointestinal Tract ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Nutrient Sensing ◽  
Enteroendocrine Cells ◽  
Cellular Mechanisms ◽  
Channel Modulation ◽  
Gut Hormone ◽  
Nutrient Utilisation ◽  
Glucagon Like Peptide 1

The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile.

scholarly journals Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 174
Author(s):  
Anne Christin Meyer-Gerspach ◽  
Jürgen Drewe ◽  
Wout Verbeure ◽  
Carel W. le Roux ◽  
Ludmilla Dellatorre-Teixeira ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gastric Emptying ◽  
Blood Lipids ◽  
Tap Water ◽  
Hormone Secretion ◽  
Gastrointestinal Symptoms ◽  
Gut Hormones ◽  
Double Blind ◽  
Gut Hormone ◽  
Dose Dependent

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

scholarly journals The Function of Gastrointestinal Hormones in Obesity—Implications for the Regulation of Energy Intake

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1839
Author(s):  
Mona Farhadipour ◽  
Inge Depoortere
Keyword(s):  
Energy Homeostasis ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Enteroendocrine Cells ◽  
Hormone Balance ◽  
Gut Hormone ◽  
Control Food ◽  
Induce Weight Loss ◽  
Novel Strategy ◽  
Control Food Intake

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity.

scholarly journals P-O01 A patient education video to support the management of post-gastrectomy / oesophagectomy syndromes

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Geoffrey Roberts ◽  
Andrew Stone ◽  
Nicola Sunderland ◽  
Sam Grimes ◽  
Frank Reimann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Patient Education ◽  
Hormone Secretion ◽  
Eating Behaviour ◽  
Physiological Basis ◽  
Upper Gi ◽  
Gut Hormone ◽  
Patient Representatives ◽  
Upper Gi Cancer ◽  
Nutritional Strategies

Abstract Background Oesophagectomy and gastrectomy result in profound and life-long changes in eating behaviour and appetite, and significant post-prandial symptoms. Despite decades of research, and recent advantages in the understanding of gut physiology, medical approaches to post-resectional patient care remain limited. The mainstay of treatment is patient education. Using clinical and lab-based studies, we investigated the effects of altered gut hormone secretion in patients after surgery for oesophageal and gastric cancer. We then produced a partially animated patient information video to better equip our patients to manage their altered alimentation. Methods The scientific background to the video was previously presented at AUGIS, and published. Studies included examination of eating behaviour, post-prandial symptoms, glucose homeostasis, gut hormone profiles and intestinal transcriptomic / peptidomic changes in a cohort of patients after oesophagectomy and gastrectomy. The movie storyboard and script were written by a team of surgeons, dietitians, patient representatives, clinical scientists and communications specialists. The goal was to communicate the physiological basis of altered eating in post-operative patients and appropriate nutritional strategies. Results The video is now freely available on Vimeo at: https://vimeo.com/356892336 It is in routine use for pre- and post-operative patient education. Conclusions Multimedia patient education is a useful tool to help manage the late effects of upper GI cancer treatment.

Proximal and distal gut hormone secretion in slow transit constipation

2000 ◽  
Vol 118 (4) ◽  
pp. A297
Author(s):  
C. Penning ◽  
J.B. Delemarre ◽  
I. Biemond ◽  
C.B. Lamers ◽  
A.A. Masclee
Keyword(s):  
Hormone Secretion ◽  
Slow Transit Constipation ◽  
Gut Hormone ◽  
Slow Transit ◽  
Transit Constipation

scholarly journals Simultaneously Quantitative Analysis of Naringin and Its Major Human Gut Microbial Metabolites Naringenin and 3-(4′-Hydroxyphenyl) Propanoic Acid via Stable Isotope Deuterium-Labeling Coupled with RRLC-MS/MS Method

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4287 ◽  
Author(s):  
Taobin Chen ◽  
Hao Wu ◽  
Yan He ◽  
Wenjun Pan ◽  
Zenghao Yan ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Propanoic Acid ◽  
Microbial Metabolites ◽  
Deuterium Labeling ◽  
Human Gut ◽  
Matrix Interferences ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Long Time ◽  
Active Precursor

Widespread in citrus fruits, naringin, a natural 2,3-dihydroflavonoid, is of particular interest to scientists and has a broad range of beneficial bioactivities to health. Orally administered naringin remains in the gut tract for a relatively long time because of its low bioavailability. Under the metabolism mediated by human gut microbiota, naringin could be an active precursor for derived metabolites to play important physiological roles. However, naringin and its metabolites are hard to accurately quantify due to severe endogenic interference. In this study, an analytical rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method coupled with stable isotope deuterium-labeling is developed and validated to simultaneously quantify naringin as well as its major human gut microbial metabolites naringenin and 3-(4′-hydroxyphenyl) propanoic acid. By eliminating the matrix interferences, this strategy not only confirms naringenin and 3-(4′-hydroxyphenyl) propanoic acid as the predominant metabolites which contribute to the pharmacological effects of naringin but also provides a suitable choice for other flavonoid pharmacokinetics study.

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