Verdu EF, Bercik P, Verma-Gandhu M, et al. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice

Intestinal Disease Research Program, McMaster University, 1200 Main S West, Hamilton, Ontario, Canada.
Gut (Impact Factor: 14.66). 03/2006; 55(2):182-90. DOI: 10.1136/gut.2005.066100
Source: PubMed


Abdominal pain and discomfort are common symptoms in functional disorders and are attributed to visceral hypersensitivity. These symptoms fluctuate over time but the basis for this is unknown. Here we examine the impact of changes in gut flora and gut inflammatory cell activity on visceral sensitivity.
Visceral sensitivity to colorectal distension (CRD) was assessed at intervals in healthy mice for up to 12 weeks, and in mice before and after administration of dexamethasone or non-absorbable antibiotics with or without supplementation with Lactobacillus paracasei (NCC2461). Tissue was obtained for measurement of myeloperoxidase activity (MPO), histology, microbiota analysis, and substance P (SP) immunolabelling.
Visceral hypersensitivity developed over time in healthy mice maintained without sterile precautions. This was accompanied by a small increase in MPO activity. Dexamethasone treatment normalised MPO and CRD responses. Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity. Administration of Lactobacillus paracasei in spent culture medium normalised visceral sensitivity and SP immunolabelling, but not intestinal microbiota counts.
Perturbations in gut flora and in inflammatory cell activity alter sensory neurotransmitter content in the colon, and result in altered visceral perception. Changes in gut flora may be a basis for the variability of abdominal symptoms observed in functional gastrointestinal disorders and may be prevented by specific probiotic administration.

Download full-text


Available from: Yukang K Mao
  • Source
    • "Embryonic and postnatal stages were calculated with the day of vaginal plug detection as E0 and with the day of birth of offspring as P0. We attempted to deplete mice of their gut microbiota by providing a combination of non-absorbable AB according to the published protocols[4,5,13]. Non-absorbable AB become concentrated in the gastrointestinal tract, thereby reducing the production of intestinal microbiota with limited serum concentrations[14,15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7±3.4%) than in control offspring (42.1±6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2±5.0%) than in control offspring (16.4±3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7-8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.
    Full-text · Article · Jan 2016 · PLoS ONE
    • "Common animal facilities are equipped to breed " conventional animals " that are populated by a very diverse microbiota, potentially also containing pathobionts, depending on the hygiene level of each facility. A substantial reduction of the microbiota can be achieved by oral application of a mixture of selectively acting antibiotics ; however, using this approach the microbiota cannot be eliminated entirely, and often a dysbiosis arises (Verdu et al., 2006). The term specific pathogen free (SPF) defines the absence of common rodent pathogens but indicates very little about the true composition of the microbiota. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gnotobiology technology for the breeding of experimental mice originated in the first half of the twentieth century. Earlier studies conducted in germ-free animals revealed the importance of the microbiota in the development of the immune system, gut morphology, and metabolism. These seminal studies have been confirmed and complemented by recent work that exploits the use of modern gnotobiotic technology as well as the combination of high-throughput molecular techniques to study the composition and metabolic capacity of the intestinal microbiota. From a historical perspective, this chapter discusses the evolution of theory concerning complex host-microbiota interactions and probiotics species. It also reviews the current evidence for a role of maladaptive interactions in the development of disease within and beyond the gastrointestinal tract.
    No preview · Article · Dec 2015
  • Source
    • "Since DSM decreased the firing frequency of nociceptive fibres, we wondered if the TRPV1 channel was involved since this is a major receptor involved in visceral nociception (Btesh et al.,2013). Verdu et al showed that antibiotic therapy induced visceral pain hypersensitivity which was inhibited by probiotic therapy (Verdu et al., 2006). Early life treatment of rats with vancomycin resulting in an altered gut microbiome, induced heightened visceral pain perception accompanied by a decrease in spinal cord TRPV1 expression (O'Mahony et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin-evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin- and distension-evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin-evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited capsaicin-evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin-evoked excitability. The TRPV1 antagonist 6-iodonordihydrocapsaicin or the use of TRPV1 knock-out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties. Journal compilation
    Full-text · Article · Jun 2015 · The Journal of Physiology
Show more