Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice

The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells is of great interest because of the potential antidiabetic and antiobesity effects of GLP-1 and PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate, and butyrate. We show that luminal and especially vascular infusion of acetate and butyrate significantly increases colonic GLP-1 secretion, and to a minor extent also PYY secretion, but only after enhancement of intracellular cAMP. Propionate neither affected GLP-1 nor PYY secretion whether administered luminally or vascularly. A FFAR2- and FFAR3–specific agonist [( S)-2-(4-chlorophenyl)-3,3-dimethyl- N-(5-phenylthiazol-2-yl)butamide (CFMB)/ AR420626 ] had no effect on colonic GLP-1 output, and a FFAR3 antagonist ( AR399519 ) did not decrease the SCFA-induced GLP-1 response. However, the voltage-gated Ca2+-channel blocker nifedipine, the KATP-channel opener diazoxide, and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses. FFAR2 receptor studies confirmed low-potent partial agonism of acetate, propionate, and butyrate, compared with CFMB, which is a full agonist with ~750-fold higher potency than the SCFAs. In conclusion, SCFAs may increase colonic GLP-1/PYY secretion, but FFAR2/FFAR3 do not seem to be involved. Rather, SCFAs are metabolized and appear to function as a colonocyte energy source.NEW & NOTEWORTHY By the use of in situ isolated perfused rat colon we show that short-chain fatty acids (SCFAs) primarily are used as a colonocyte energy source in the rat, subsequently triggering glucagon like peptide-1 (GLP-1) secretion independent of the free fatty acid receptors FFAR2 and FFAR3. Opposite many previous studies on SCFAs and FFAR2/FFAR3 and GLP-1 secretion, this experimental model allows investigation of the physiological interactions between luminal nutrients and secretion from cells whose function depend critically on their blood supply as well as nerve and paracrine interactions.

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The effectiveness of glucagon-like peptide 1 receptor agonist and prebiotic on short-chain fatty acids and carbohydrate metabolism in patients with carbohydrate metabolism violation

Endocrine Abstracts ◽

10.1530/endoabs.70.aep464 ◽

2020 ◽

Author(s):

Lilit Egshatyan ◽

Nane Khachaturian ◽

Svetlana Silvestrova ◽

Ashot Mkrtumyan

Keyword(s):

Fatty Acids ◽

Carbohydrate Metabolism ◽

Receptor Agonist ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Chain Fatty Acids

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The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids

Scientific Reports ◽

10.1038/s41598-019-56743-x ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 5

Author(s):

Sarah Ducastel ◽

Véronique Touche ◽

Mohamed-Sami Trabelsi ◽

Alexis Boulinguiez ◽

Laura Butruille ◽

...

Keyword(s):

Fatty Acids ◽

Nuclear Receptor ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Chain Fatty Acids

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Faculty Opinions recommendation of Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725300895.793509795 ◽

2015 ◽

Author(s):

Jonathan Kaunitz

Keyword(s):

Fatty Acids ◽

T Cells ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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The Consumption of Galactomannan Effervescent Drinks made from Coconut Pulp Waste and Colonic Microbiota in Wistar Rats

International Journal of Probiotics and Prebiotics ◽

10.37290/ijpp2641-7197.15:52-56 ◽

2020 ◽

Vol 15 (1) ◽

pp. 52-56

Author(s):

Sri Winarti ◽

Agung Pasetyo

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Wistar Rats ◽

Short Chain Fatty Acids ◽

Short Chain ◽

E Coli ◽

Colonic Microbiota ◽

Male Wistar Rats ◽

Lactobacillus Spp ◽

Chain Fatty Acids

The consumption of prebiotics is known to affect the balance of gut microbiota. The purpose of this study was to explore how a galactomannan-rich effervescent drink can affect the population of Lactobacillus, Bifidobacterium, E. coli, and the concentration of short-chain fatty acids in the cecum of rats. Twenty-eight male Wistar rats (aged 2 months) were divided equally into 7 groups and treated orally each day for 15 days with 2 mL effervescent drinks with increasing levels of prebiotic galactomannan. The dosage of 500 mg galactomannan increased the growth of Lactobacillus spp. and Bifidobacterium spp. with inhibition of the growth of E.coli with increased formation of short-chain fatty acids such as acetate, propionate, and butyrate in the cecum of rats.

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Impact of oral COMT-inhibitors on gut microbiota and short chain fatty acids in Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2019.11.020 ◽

2020 ◽

Vol 70 ◽

pp. 20-22 ◽

Cited By ~ 1

Author(s):

Daniel Grün ◽

Valerie C. Zimmer ◽

Jil Kauffmann ◽

Jörg Spiegel ◽

Ulrich Dillmann ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Comt Inhibitors ◽

Chain Fatty Acids

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Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation

Nutrients ◽

10.3390/nu13051427 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1427

Author(s):

Junhui Zhang ◽

Fengqin Feng ◽

Minjie Zhao

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Dose Group ◽

Low Dose ◽

Short Chain Fatty Acids ◽

Normal Diet ◽

Short Chain ◽

High Dose ◽

Dose Treatment ◽

Chain Fatty Acids

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg−1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.

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Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease

Molecular Neurodegeneration ◽

10.1186/s13024-021-00427-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Velma T. E. Aho ◽

Madelyn C. Houser ◽

Pedro A. B. Pereira ◽

Jianjun Chang ◽

Knut Rudi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Inflammatory Responses ◽

Disease Onset ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Chain Fatty Acids

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

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The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

Acta Diabetologica ◽

10.1007/s00592-021-01727-5 ◽

2021 ◽

Author(s):

Dominic Salamone ◽

Angela Albarosa Rivellese ◽

Claudia Vetrani

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Gut Microbiota ◽

Dietary Fibre ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Microbiota Composition ◽

The Relationship ◽

Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

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