Rectal Instillation of Butyrate Provides a Novel Clinically Relevant Model of Noninflammatory Colonic Hypersensitivity in Rats

Bourdu, Sophie; Dapoigny, Michel; Chapuy, Eric; Artigue, Fabrice; Vasson, Marie‐Paule; Déchelotte, Pierre; Bommelaer, Gilles; Eschalier, Alain; Ardid, Denis

doi:10.1053/j.gastro.2005.03.082

Cited by 153 publications

(140 citation statements)

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“…However, the extent to which changes in the soma compared with peripheral or central terminals and synapses are responsible for the modulation of behavioral sensitization cannot be deduced from the present study. Our results add to an increasing list (9,17,21) of animal models where sensory pathway sensitization is induced in the absence of overt induction of chronic inflammation by chemical irritants or infection.…”

Section: Discussionsupporting

confidence: 54%

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Ma¹,

Mao²,

Wang³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kunze W. Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli. Am J Physiol Gastrointest Liver Physiol 296: G868 -G875, 2009. First published January 29, 2009 doi:10.1152/ajpgi.90511.2008.-Lactobacillus species ingestion can decrease autonomic responses and spinal fiber discharge to nociceptive colorectal distension (CRD), even in the absence of inflammation. The present study aimed to determine whether dorsal root ganglion (DRG) somas could be a locus where the antinociceptive probiotic may have an effect. Healthy rats were fed with Lactobacillus reuteri or vehicle control for 9 days whereupon they were anesthetized, and intermittent distal colonic CRD at 80 mmHg distension was either performed for 1 h or not. The animals were immediately euthanized and patch-clamp recordings taken after isolation and overnight culture from those DRG that projected to the distal colon. CRD decreased the threshold for action potential generation and increased the number of spikes discharged during a standard depolarizing test stimulus, and this effect was blocked by prior probiotic ingestion. The increase in excitability was paralleled by an increase in DRG capacitance, which was not altered by Lactobacillus reuteri ingestion. CRD did not increase tissue weight or myeloperoxidase activity. We suggest that the effects of CRD may have been caused by activity-dependent neurotransmission between DRG somas. CRD evoked increases in action potential upstroke speed, which suggests that it may also have led to augmentation of sodium channel conductances. Probiotic ingestion may have interfered with this hypothetical mechanism since it blocked the effect of CRD on the action potential. colorectal distension; dorsal root ganglion; probiotics; sensory neurons PROBIOTICS ARE HEALTH-PROMOTING commensal bacteria that can have therapeutic or preventative roles when ingested. Probiotics are most frequently of the Lactobacillus or Bifidobacterium species, and clinically beneficial effects of probiotics have been described in travelers' diarrhea, irritable bowel syndrome, and inflammatory bowel disease (13,29,35,44,46). In addition, probiotics can modulate postinflammatory gut hypersensitivity and alter neuropeptide content (20,43). Because of their therapeutic potential and their presumed consumer safety, the actions of probiotics on the physiological mechanisms underlying peripheral and centrally directed nociceptive signals are increasingly being investigated.Ingestion of probiotic commensals can decrease colorectal distension (CRD)-evoked pain in healthy animals, that is, in the absence of overt inflammation in the intestine. Experimental modulation of intestinal motility (32) and visceral pain (18,32,43) by Lactobacillus species have been convincingly demonstrated for the murine colon. Lactobacillus reuteri (L. reuteri) ingestion can alter the excitability of myenteric intrinsic sensory neurons that were recorded from colon segments taken from healthy rats. Remarkably, in anesthetized he...

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Section: Discussionsupporting

confidence: 54%

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Ma¹,

Mao²,

Wang³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Similarly, in the study of Malinen et al (2005), all IBS subgroups had elevated levels of Veillonella spp., C. coccoides and R. productus, all able to produce acetate and succinate (Liu et al, 2008). However, as IBS-D patients have also been documented to have more butyrate but less total SCFAs than HCs (Treem et al, 1996), and as butyrate induces visceral hypersensitivity in a rat model (Bourdu et al, 2005), the clinical effects of organic acids in IBS remain to be verified.…”

Section: Functional Perspective On Ibs-related Microbiotamentioning

confidence: 99%

Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives

2010

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that has been associated with aberrant microbiota. This review focuses on the recent molecular insights generated by analysing the intestinal microbiota in subjects suffering from IBS. Special emphasis is given to studies that compare and contrast the microbiota of healthy subjects with that of IBS patients classified into different subgroups based on their predominant bowel pattern as defined by the Rome criteria. The current data available from a limited number of patients do not reveal pronounced and reproducible IBS-related deviations of entire phylogenetic or functional microbial groups, but rather support the concept that IBS patients have alterations in the proportions of commensals with interrelated changes in the metabolic output and overall microbial ecology. The lack of apparent similarities in the taxonomy of microbiota in IBS patients may partially arise from the fact that the applied molecular methods, the nature and location of IBS subjects, and the statistical power of the studies have varied considerably. Most recent advances, especially the finding that several uncharacterized phylotypes show non-random segregation between healthy and IBS subjects, indicate the possibility of discovering bacteria specific for IBS. Moreover, tools are being developed for the functional analysis of the relationship between the intestinal microbiota and IBS. These approaches may be instrumental in the evaluation of the ecological dysbiosis hypothesis in the gut ecosystem. Finally, we discuss the future outlook for research avenues and candidate microbial biomarkers that may eventually be used in IBS diagnosis. IntroductionWe are colonized from birth by a complex microbiota that affects health and disease. By far the greater part of this microbiota resides in the gastrointestinal (GI) tract, and can be considered as an organ within an organ (Bocci, 1992). As many of the GI tract microbes have not yet been cultured and are only recognized based on their 16S rDNA sequences, molecular high-throughput approaches have been developed to study the diversity and functionality of the thousands of phylotypes that have been predicted to be present in the GI tract (for a full review, see Zoetendal et al., 2008). These studies have revealed that the composition of the microbiota in healthy adults is highly subject-specific and stable, indicating an individual core. Comparative microbiota analyses between multiple healthy subjects indicate that a limited proportion of phylotypes are shared between individuals, forming a common core microbiota that is assumed to be functionally redundant (Qin et al., 2010;Tap et al., 2009;Turnbaugh et al., 2009). Recent metagenomic sequence analysis of the GI tract microbiota has confirmed this and defined a reference set of over three million unique genes that vastly exceeds the coding capacity of the human genome (Qin et al., 2010). Insight into the microbiota of healthy subjects allows comparisons with that of compromised...

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“…Although the mechanism(s) for the leftward shift of P2X 3 -agonists concentration-response curves in c-DRG neurons after zymosan treatment is unclear, it is noteworthy that P2X 3 function can be upregulated by calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF), both of which are known to participate in visceral pain in IBS models (Barreau et al 2008;Bourdu et al 2005). CGRP stimulates trafficking of P2X 3 receptors from intracellular stores to the cell membrane via protein-kinase-A-and protein-kinase-C-dependent mechanisms (Fabbretti et al 2006), and NGF rescues P2X 3 from an inhibitory control of conductance by C-terminal Src inhibitory kinase-dependent phosphorylation (D'Arco et al 2009).…”

Section: Purinergic Responses and Colorectal Hypersensitivitymentioning

confidence: 99%

Altered Purinergic Signaling in Colorectal Dorsal Root Ganglion Neurons Contributes to Colorectal Hypersensitivity

Shinoda

La²,

Bielefeldt

et al. 2010

Journal of Neurophysiology

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Shinoda M, La JH, Bielefeldt K, Gebhart GF. Altered purinergic signaling in colorectal dorsal root ganglion neurons contributes to colorectal hypersensitivity. J Neurophysiol 104: 3113-3123, 2010. First published September 22, 2010 doi:10.1152/jn.00560.2010. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by pain and hypersensitivity in the relative absence of colon inflammation or structural changes. To assess the role of P2X receptors expressed in colorectal dorsal root ganglion (c-DRG) neurons and colon hypersensitivity, we studied excitability and purinergic signaling of retrogradely labeled mouse thoracolumbar (TL) and lumbosacral (LS) c-DRG neurons after intracolonic treatment with saline or zymosan (which reproduces 2 major features of IBSpersistent colorectal hypersensitivity without inflammation) using patch-clamp, immunohistochemical, and RT-PCR techniques. Although whole cell capacitances did not differ between LS and TL c-DRG neurons and were not changed after zymosan treatment, membrane excitability was increased in LS and TL c-DRG neurons from zymosan-treated mice. Purinergic agonist adenosine-5=-triphosphate (ATP) and ␣,␤-methylene ATP [␣,␤-meATP] produced inward currents in TL c-DRG neurons were predominantly P2X 3 -like fast (ϳ70% of responsive neurons); P2X 2/3 -like slow currents were more common in LS c-DRG neurons (ϳ35% of responsive neurons). Transient currents were not produced by either agonist in c-DRG neurons from P2X 3 Ϫ/Ϫ mice. Neither total whole cell Kv current density nor the sustained or transient Kv components was changed in c-DRG neurons after zymosan treatment. The number of cells expressing P2X 3 protein and its mRNA and the kinetic properties of ATP-and ␣,␤-meATPevoked currents in c-DRG neurons were not changed by zymosan treatment. However, the EC 50 of ␣,␤-meATP for the fast current decreased significantly in TL c-DRG neurons. These findings suggest that colorectal hypersensitivity produced by intracolonic zymosan increases excitability and enhances purinergic signaling in c-DRG neurons.

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Rectal Instillation of Butyrate Provides a Novel Clinically Relevant Model of Noninflammatory Colonic Hypersensitivity in Rats

Cited by 153 publications

References 65 publications

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives

Altered Purinergic Signaling in Colorectal Dorsal Root Ganglion Neurons Contributes to Colorectal Hypersensitivity

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