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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity.
Soldavini, J, Kaunitz, JD
Digestive diseases and sciences. 2013;(10):2756-66
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Abstract
BACKGROUND The lumen of the gastrointestinal tract contains many substances produced from the breakdown of foodstuffs, from salivary, esophageal, intestinal, hepatic, and pancreatic secretions, and from sloughed cells present in the gastrointestinal lumen. Although these substances were traditionally regarded as waste products, there is increasing realization that many can be biologically active, either as signalling compounds or as nutrients. For example, proteins are broken down into amino acids, which are then sensed by nutrient receptors. The gut microbiome, which is at highest abundance in the ileocecum, has powerful metabolic activity, digesting and breaking down unabsorbed carbohydrates, proteins, and other ingested nutrients into phenols, amines, volatile organic compounds, methane, carbon dioxide, hydrogen, and hydrogen sulfide into volatile fatty acids, also called short-chain fatty acids (SCFAs). CONCLUSION These latter substances are the topic of this review. In this review, we will briefly discuss recent advances in the understanding SCFA production, signalling, and absorption, followed by a detailed description and discussion of trials of SCFAs, probiotics, and prebiotics in the treatment of gastrointestinal disease, in particular ulcerative colitis (UC), pouchitis, short bowel syndrome, and obesity.
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[Metabolic activity of intestinal microflora and its role in determination of nutritional support tactic after gastrectomy].
Kuz'mina, TN, Sil'vestrova, SIu, Ruchkina, IN, Petrakov, AV
Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology. 2009;(6):35-41
Abstract
Nutrition recommendations in symptoms of postgastrectomy syndroms is very different. The calculation of regimen using the parenteral and enteral alimentation may be established in the control test of definition of fecal short-chain fatty acids and microflora in such patients. Probiotics attach to the intestinal wall and protect it from the attacks of pathologic microorganisms. Probiotics are especially useful in the complex treatment of postgastrectomy syndroms.
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Probiotic-induced changes in the intestinal epithelium: implications in gastrointestinal disease.
Ramakrishna, BS
Tropical gastroenterology : official journal of the Digestive Diseases Foundation. 2009;(2):76-85
Abstract
There is resurgent interest in the use of probiotics to maintain gastrointestinal and systemic health, driven by recent advances in knowledge of bacterial interactions with the epithelium and innate immune system of the intestine. The effects of probiotic bacteria on the intestinal epithelium and their downstream consequences are reviewed. Probiotics prevent pathogen adherence and invasion of the epithelium, partly by blocking adherence sites but also by upregulating gene expression of MUC2 and of antimicrobial peptides. Metabolic effects of probiotics on the intestinal epithelium include production of short chain fatty acids which influence epithelial cell metabolism, turnover and apoptosis. Bacterial metabolism of unabsorbed dietary constituents with production of free radicals and phenolic metabolites can lead to DNA damage and cancer; probiotics restore eubiosis and potentially prevent this. Probiotics alter expression and redistribution of tight junction proteins and reduce intestinal permeability limiting absorption of noxious molecules from the gut lumen. Most studied are the effects of probiotics on epithelial cells which are the first line of innate immune-capable cells that encounter luminal flora. Probiotics, through secreted molecules, influence the innate inflammatory response of epithelial cells to stimuli from the gut lumen, and reduce mucosal inflammation. Through effects on dendritic, and possibly epithelial, cells they influence naïve T cells in the lamina propria of the gut and thus influence adaptive immunity. These varied effects of probiotics have implications for the treatment of several gastrointestinal diseases including antibiotic-associated colitis, acute gastroenteritis, inflammatory bowel disease, colon cancer, and irritable bowel syndrome.
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Intestinal permeability and systemic infections in critically ill patients: effect of glutamine.
De-Souza, DA, Greene, LJ
Critical care medicine. 2005;(5):1125-35
Abstract
OBJECTIVE This article provides a critical review of the evidence indicating that an increase in intestinal permeability is associated with the installation of bacteremia, sepsis, and the multiple organ failure syndrome and that glutamine in pharmacologic doses reduces the acute increase of intestinal permeability and the infection frequency in critically ill patients. DATA SOURCE All studies published until December 2004 about intestinal permeability, bacterial translocation, and glutamine were located by search of PubMed and Web of Science. The reference lists of review articles and primary publications were also examined to identify references not detected in the computer search. STUDY SELECTION Clinical and experimental studies investigating the correlation between intestinal permeability, bacterial translocation, and frequency of infections, associated or not with the effect of glutamine administration. DATA EXTRACTION Information regarding patient population, experimental design, glutamine doses and routes of administration, nutritional therapy prescribed, methods used to assess intestinal permeability, metabolic variables, and the frequency of infections were obtained from the primary literature. DATA SYNTHESIS Intestinal permeability is increased in critically ill patients. The results have not always been consistent, but the studies whose results support the association between intestinal permeability and systemic infections have had better design and more appropriate controls. The administration of glutamine by the intravenous or oral route and at the doses recommended before or immediately after surgery, burns, or the administration of parenteral nutrition has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine reduces the frequency of systemic infections and may also reduce the translocation of intestinal bacteria and toxins, but this has not been demonstrated. CONCLUSIONS Glutamine administration improves the prognosis of critically ill patients presumably by maintaining the physiologic intestinal barrier and by reducing the frequency of infections.