The relationship between the effects of short‐chain fatty acids on intestinal motility <i>in vitro</i> and GPR43 receptor activation

Dass, Narinder B.; John, Axel; Bassil, Anna K.; Crumbley, Christopher W.; Shehee, W R; Maurio, Frank; Moore, Gary B.T.; Taylor, Carol M.; Sanger, Gareth J.

doi:10.1111/j.1365-2982.2006.00853.x

Cited by 151 publications

(125 citation statements)

References 37 publications

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“…Gene expression levels of both GPR41 and GPR43 in the stomach and small intestine are comparatively lower than other tissues including spleen, bone marrow and other tissues (1,11). On the other hand, quantitative real-time PCR revealed that GPR43 gene expression in the large intestine was higher than in other regions of the GI tract (5). Furthermore, we recently reported the presence of GPR43 in the rat terminal ileum and colon (8) and human colon as well as its gene and protein expression patterns (9).…”

Section: Methodsmentioning

confidence: 94%

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Expression of short-chain fatty acid receptor GPR41 in the human colon

et al. 2009

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Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are the most commonly found anions found in the monogastric mammalian large intestine, and are known to have a variety of physiological and pathophysiological effects on the gastrointestinal tract. We investigated the protein and mRNA expression levels of GPR41, a possible G protein coupled receptor for SCFA, using Western blot analysis and reverse transcriptase-polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41 protein is localized in cytoplasm of enterocytes and enteroendocrine cells. Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not serotonin or GPR43. The cellular population of GPR41 (0.01 ± 0.01 cells/crypt) was much smaller than that of GPR43 (0.33 ± 0.01 cells/crypt) in the human colon. However, the potency order of SCFA-induced phasic contraction of colonic smooth muscle that we previously reported is consistent with GPR41 (propionate ≧ butyrate > acetate) but not GPR43 (propionate = butyrate = acetate). Therefore, the present study suggests that GPR41 expressed in human colonic mucosa may function as a sensor for luminal SCFAs.Short-chain fatty acids (SCFA) are a major anion present in the large intestinal lumen of monogastric mammals including humans. SCFAs are produced during anaerobic bacterial fermentation of unabsorbed carbohydrates and dietary fibers. The concentration of SCFAs in human feces is reported to be approximately 100 mM, and are primarily comprised of acetate, propionate, and butyrate. Molar ratios of SCFAs in human fecal content are 50-60, 15-20, and 10-20 for acetate, propionate, and butyrate respectively (3, 22). Through absorption and metabolism of SCFAs, the host is able to salvage energy from food not digested in the upper intestine. Furthermore, luminal SCFAs have various physiological and pathophysiological effects in the gastrointestinal (GI) tract (4,10,17,19). In our previous studies, we demonstrated that SCFAs evoke two different effects on rat colonic smooth muscle in vitro (13)(14)(15). In the early phase, propionate and butyrate induced concentrationdependent phasic contractions in circular and longitudinal muscle, but acetate had no such effect (13-15). In the late phase, propionate induced a concentration-dependent increase in frequency of spontaneous contractions in circular (13) and longitudinal muscle (15), but butyrate did not affect the frequency of spontaneous longitudinal muscle contractions (15). On the other hand, acetate induced a

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Section: Methodsmentioning

confidence: 94%

“…The rabbits were bled from the marginal ear vein, ten days after each immunization. After six immunizations, one of the three rabbits revealed a high titer antiserum (RY1494) against human GPR41 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and was used for the present study.…”

Section: Methodsmentioning

confidence: 99%

Expression of short-chain fatty acid receptor GPR41 in the human colon

et al. 2009

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“…The mechanisms for this are thought to be related to alterations in the intestinal microflora and production of short chain fatty acids SCFA, which biological and clinical properties have been extensively investigated [22,23]. SCFA stimulate the motility of the intestine probably through colonic motility by stimulating mucosal receptors connected to enteric and vagal nerves [56], colonic smooth muscle [57], and releasing gastrointestinal regulatory peptides that modulate intestinal motility such as polypeptide YY [58]. The motility of the GIT is important for absorption, transport, and clearance.…”

Section: Chronic Constipationmentioning

confidence: 99%

Probiotics for Human and Poultry Use in the Control of Gastrointestinal Disease: A Review of Real-World Experiences

Téllez¹,

Rodríguez‐Fragoso²,

Va³

et al. 2013

Altern Integ Med

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Over a century ago Eli Metchnikoff proposed the revolutionary idea to consume viable bacteria to promote health by modulating the intestinal microflora. The idea is more applicable now than ever, since bacterial antimicrobial resistance has become a serious worldwide problem both in medical and agricultural fields. The interest in digestive physiology and the microbiome has generated data whereby well being of all living organisms with a digestive tract can be enhanced and the risk of disease reduced. Given the recent international legislation and domestic consumer pressures to withdraw growth-promoting antibiotics and limit antibiotics available for treatment of bacterial infections, probiotics can offer alternative options. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Current indications are that mechanism of action involves a number of possibilities like rapid activation of innate host immune responses, assisting in the digestion of food materials etc. In this review, we focused on applying probiotic concept to alleviate chronic constipation and idiopathic diarrhea in humans or for specific pathogen reduction and improvement of GIT diseases in poultry.

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“…Within the human colon, concentrations of acetate, propionate and butyrate were reported to be in the range of 20-43 mmol/L, 6-13 mmol/L and 6-15 mmol/L, respectively [21] . GPR43 has been reported to be expressed in human, mouse and rat colons [22][23][24] . Induction of antiinflammatory activities by SCFAs in the colon may contribute to the bacterial evasion of the immune system [25] .…”

Section: Introductionmentioning

confidence: 99%

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

Cox¹,

Jackson²,

Stanton³

et al. 2009

WJG

329

244

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AIM:To investigate the effect of short-chain fatty acids (SCFAs) on production of prostaglandin E2 (PGE2), cytokines and chemokines in human monocytes. METHODS:Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction. The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells (PBMC) was studied by measuring PGE2, cytokines and chemokines in the supernatant.The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS:Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide (LPS). In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 (MCP-1) production and LPS-induced interleukin-10 (IL-10) production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-γ in human PBMC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws (P < 0.01). CONCLUSION:SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.

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The relationship between the effects of short‐chain fatty acids on intestinal motility in vitro and GPR43 receptor activation

Cited by 151 publications

References 37 publications

Expression of short-chain fatty acid receptor GPR41 in the human colon

Expression of short-chain fatty acid receptor GPR41 in the human colon

Probiotics for Human and Poultry Use in the Control of Gastrointestinal Disease: A Review of Real-World Experiences

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

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