Nutrient Control of Energy Homeostasis via Gut-Brain Neural Circuits

Mithieux, Gilles

doi:10.1159/000369070

Cited by 19 publications

(13 citation statements)

References 49 publications

(63 reference statements)

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“…Though the liver is the primary site of GNG, this pathway is also induced in the intestine and kidneys during specific conditions. Intestinal GNG is a central signal in glucose and energy homeostasis [33]. We observed no significant change in the expression levels of glucogenic amino acids, which indicates GNG is not induced by a substrate effect putatively initiated by these amino acids as substrates (Additional file 1: Figure S8).…”

Section: Discussionmentioning

confidence: 69%

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Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis

et al. 2017

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BackgroundOrganophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process.ResultsHere we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes.ConclusionCollectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1134-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 69%

“…5a and b). Intestinal GNG was shown to induce benefits in glucose control since it initiates a neutrally mediated suppression of hepatic glucose production [33]. However, when hepatic GNG is strongly altered, e.g.…”

Section: Discussionmentioning

confidence: 99%

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis

et al. 2017

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“…Dietary protein and soluble fibre may influence energy and glucose homeostasis through the induction of intestinal gluconeogenesis that is sensed by neural receptors in the wall of the portal vein (Mithieux, 2014;Mithieux et al, 2005). Intestinal gluconeogenesis and release into the portal vein may play a key role in hunger, satiety, and endogenous glucose production through influences on hepatic insulin sensitivity.…”

Section: Portal Vein Nutrient Sensingmentioning

confidence: 99%

Neuroendocrine adaptations to bariatric surgery

Dixon

Lambert

2015

Molecular and Cellular Endocrinology

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“…74 It is also imperative to speculate that changes in the gut-brain neural circuit activities because of altered gut neuropeptides after small bowel resection, may play an important role in the adaptation process with possible enhancement of intestinal gluconeogenesis and gut homeostasis. 75,76 Concrete data concerning the above described adaptive changes are sparse with the exact underlying mechanisms remain to be fully elucidated. 71 Nonetheless, the extent of gut adaptation is commonly influenced by the site and extent of bowel resection, initiation of enteral feeding, growth of beneficial intestinal microbiota, and stimulation of endogenous enterotrophic factors including glucagon-like peptide 2.…”

Section: Surgical Resection and Intestinal Adaptationmentioning

confidence: 99%

Management of Crohnʼs Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation

Nyabanga

Kochhar

Costa

et al. 2016

Inflammatory Bowel Diseases

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Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.

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Nutrient Control of Energy Homeostasis via Gut-Brain Neural Circuits

Cited by 19 publications

References 49 publications

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis

Neuroendocrine adaptations to bariatric surgery

Management of Crohnʼs Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation

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