IntroductionProbiotics are live non-pathogenic commensal organisms that promote beneficial health effects when ingested [1]. Organisms used as probiotics are most frequently of the Lactobacillus or Bifidobacterium species, and clinically beneficial effects of probiotics have been described in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease [2][3][4][5][6]. Although experimental modulation of intestinal motility [7] and visceral pain [7][8][9] Abstract Probiotics are live non-pathogenic commensal organisms that exert therapeutic effects in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease. Little is known about mechanisms of action of commensal bacteria on intestinal motility and motilityinduced pain. It has been proposed that probiotics affect intestinal nerve function, but direct evidence for this has thus far been lacking. We hypothesized that probiotic effects might be mediated by actions on colonic intrinsic sensory neurons. We first determined whether

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...