The intestinal microbiota and chronic disorders of the gut

Dupont, Andrew; DuPont, Herbert L.

doi:10.1038/nrgastro.2011.133

Cited by 266 publications

(194 citation statements)

References 119 publications

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“…9,10,22,28,29,[34][35][36][37][38] Our recent study highlights a novel area of influence for gut microbes and SCFAs-blood pressure control.…”

Section: Discussionmentioning

confidence: 99%

“…A recent and growing body of literature demonstrates that gut microbiota-derived metabolites play important roles in regulating the physiology of the host, and have been implicated in pathophysiological processes as varied as immune disorders, 10,[28][29][30] metabolism, [31][32][33] atherosclerosis, 34 irritable bowel syndrome, 35,36 and chronic kidney disease. 37,38 Gut microbes produce SCFAs (chiefly acetate, propionate and butyrate) such that the concentration in the colon is approximately 100mM.…”

Section: Scfas: the Gut Microbiotamentioning

confidence: 99%

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A novel SCFA receptor, the microbiota, and blood pressure regulation

2013

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T he maintenance of blood pressure homeostasis is a complex process which is carefully regulated by a variety of inputs. We recently identified two sensory receptors (Olfactory receptor 78 and G protein couple receptor 41) as novel regulators of blood pressure. Both Olfr78 and Gpr41 are receptors for short chain fatty acids (SCFAs), and we showed that propionate (a SCFA) modifies blood pressure in a manner which is differentially modulated by the absence of either Olfr78 or Gpr41. In addition, propionate modifies renin release in an Olfr78-dependent manner. Our study also demonstrated that antibiotic treatment modulates blood pressure in Olfr78 null mice, indicating that SCFAs produced by the gut microbiota likely influence blood pressure regulation. In this addendum, we summarize the findings of our recent study and provide a perspective on the implications of the interactions between the gut microbiota and blood pressure control. IntroductionA recent paradigm in sensory physiology suggests that "sensory" receptors (taste receptors, olfactory receptors, and many other G-protein coupled receptors) play important roles in non-sensory tissues, where they serve as selective and sensitive chemoreceptors. For example, sour taste receptors function in the tongue to sense changes in pH as an indicator of sour taste 1,2 -in addition, these receptors are also found in neurons which contact the central canal of the spinal column, where they function to detect changes in pH in cerebrospinal fluid.1 In addition, olfactory receptors (ORs) participate in muscle cell migration 3 and sperm chemotaxis, 4 sweet taste receptors are found in the bladder, 5 and bitter taste receptors mediate both bronchodilation and ciliary beat frequency in airways.6,7 G-protein coupled receptors of the GPR gene family are also known to act as sensors of metabolites. [8][9][10][11][12] Intriguingly, ligands for these sensory receptors are often generated by physiological processes or metabolic pathways, 1,8,12,13 suggesting that known metabolites or chemicals may have signaling functions beyond their traditional roles. 8,12,13 Furthermore, sensory receptors such as ORs are expressed in a variety of tissues in mice, humans, and other primates, where their functional role has not yet been defined. 14-16 Localization of Renal Olfactory Receptor Olfr78We previously identified Olfactory Receptor 78 (Olfr78) as a "renal" olfactory receptor (OR), 17 and in a recent study 18 we set out to localize and to identify the ligand for this OR. We took advantage of a β-galactosidase reporter mouse model in order to localize Olfr78, and determined that Olfr78 is found in vascular resistance beds in a variety of tissues, as well in the renal afferent arteriole. The renal afferent arteriole is an incredibly specialized vessel: blood enters the renal glomerulus for filtration via the afferent arteriole, and this arteriole is the site where renin (the initial, rate-limiting step in the renin-angiotensin-aldosterone pathway) is stored for eventual release into the blood...

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“…9,10,22,28,29,[34][35][36][37][38] Our recent study highlights a novel area of influence for gut microbes and SCFAs-blood pressure control.…”

Section: Discussionmentioning

confidence: 99%

Section: Scfas: the Gut Microbiotamentioning

confidence: 99%

A novel SCFA receptor, the microbiota, and blood pressure regulation

2013

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“…Growing evidences suggest that IBS patients have a dysbiotic intestinal microbiota. 61,62 Approximately 8% of children experience recurrent functional abdominal pain and about 61% of these children continue to report abdominal pain or IBS. In childhood, recurrent abdominal pain (RAP) consists of pain symptoms similar and often indistinguishable from those in IBS suggesting that there are similar underlying pathophysiologies.…”

Section: Alterations Of the M Icrobiome In Visceral Pain Disordersmentioning

confidence: 99%

Visceral Pain and Gastrointestinal Microbiome

Chichlowski

Rudolph

2015

J Neurogastroenterol Motil

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A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the production of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. There are critical sensitive periods that can impact visceral pain responses in adulthood. In this review we provide a brief background of the intestinal microbiome and emerging concepts of the bidirectional interactions between the microbiome, gut and brain. We also discuss recent work in animal models, and human clinical trials using prebiotics and probiotics that alter the microbiome with resultant alterations in visceral pain responses.

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“…Gut microflora, a major environmental player in IBD [43,68,71]: altered immune response to otherwise 'normal' mucosal flora in IBD altered microflora in some cases of IBD: contributor to the disease, or a consequence of inflammation? Major players in IBD [43,69,70,[72][73][74]:…”

Section: Box 1 Inflammatory Bowel Diseasesmentioning

confidence: 99%