Constipation has a significant influence on quality of life. Patients with constipation have slow waves in their gastrointestinal smooth muscles and less faecal water contents, which are closely associated with down-regulation of the interstitial cells of Cajal (ICC) in the gastrointestinal muscles and the aquaporin protein AQP3 expressed in colon epithelial cells. Recent studies supported that patients with constipation have altered intestinal microbial structures compared with healthy controls. Intestinal dysbiosis might be one possible pathophysiological mechanism causing constipation. Bacterial strains, such as Lactobacillus spp., have shown many beneficial effects on the amelioration of constipation. However, few studies reported the structural changes of intestinal microbiota post-intervention of probiotics. In this study, a bacterial mixture was administrated to rats with loperamide-induced constipation. Effects of the bacterial mixture on small intestine transit (SIT), faecal water content, and the intestinal microbiome in rats were evaluated. Meanwhile, we investigated several factors involved in signalling pathways that regulate function of ICC and expression of AQP3 to discuss the possible underlying molecular mechanisms. Intervention of the bacterial mixture improved SIT and faecal water content in constipated rats. The up-regulation of C-kit/SP signalling pathways in ICC and AQP3 significantly contributed to improvements. These changes were closely associated with the manipulation of intestinal dysbiosis in constipated rats. Furthermore, our results revealed the important role of intestinal microbiota in affecting gut motility through regulation of serotonin biosynthesis. This monoamine neurotransmitter, secreted from enterochromaffin cells, up-regulated both substance P/neurokinin 1 receptors pathway of ICC and the expression of AQP3 in intestinal epithelial cells. Our study suggested that the disrupted microbiome in patients could be a potential therapeutic target for the improvement of constipation.
Chassard, C., Dapoigny, M., Scott, K.P., Crouzet, L., Del’homme, C., Marquet, P., Martin, J.C., Pickering, G., Ardid, D., Eschalier, A., Dubray, C., Flint, H.J. and Bernalier-Donadille, A., 2012. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Alimentary Pharmacology and Therapeutics 35: 828-838.
'Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome ' () 35 Alimentary Pharmacology and Therapeutics : 828 -838.
Daniel, E.E., 2001. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. III. Interaction of interstitial cells of Cajal with neuromediators: an interim assessment. American Journal of Physiology, Gastrointestinal and Liver Physiology 281: G1329-1332.
'Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside ' () 281 American Journal of Physiology, Gastrointestinal and Liver Physiology : G1329 -1332.
Ge, X., Ding, C., Zhao, W., Xu, L., Tian, H., Gong, J., Zhu, M., Li, J. and Li, N., 2017. Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility. Journal of Translational Medicine 15: 13.
'Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility ' () 15 Journal of Translational Medicine : 13.
Han, S.H., Hong, K.B., Kim, E.Y., Ahn, S.H. and Suh, H.J., 2016. Effect of dual-type oligosaccharides on constipation in loperamide-treated rats. Nutrition Research and Practice 10: 583-589.
'Effect of dual-type oligosaccharides on constipation in loperamide-treated rats ' () 10 Nutrition Research and Practice : 583 -589.
Hua, Y., Ding, S., Zhang, W., Zhou, Q., Ye, W., Chen, M. and Zhu, X., 2015. Expression of AQP3 protein in hAECs is regulated by Camp-PKA-CREB signalling pathway. Frontiers in Bioscience 20: 1047-1055.
'Expression of AQP3 protein in hAECs is regulated by Camp-PKA-CREB signalling pathway ' () 20 Frontiers in Bioscience : 1047 -1055.
Huizinga, J.D., Thuneberg, L., Kluppel, M., Malysz, J., Mikkelsen, H.B. and Bernstein, A., 1995. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373: 347-349.
'W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity ' () 373 Nature : 347 -349.
Hyland, N.P. and Cryan, J.F., 2016. Microbe-host interactions: Influence of the gut microbiota on the enteric nervous system. Developmental Biology 417: 182-187.
'Microbe-host interactions: Influence of the gut microbiota on the enteric nervous system ' () 417 Developmental Biology : 182 -187.
Ikarashi, N., Mochiduki, T., Takasaki, A., Ushiki, T., Baba, K., Ishii, M., Kudo, T., Ito, K., Toda, T., Ochiai, W. and Sugiyama, K., 2011. A mechanism by which the osmotic laxative magnesium sulphate increases the intestinal aquaporin 3 expression in HT-29 cells. Life Sciences 88: 194-200.
'A mechanism by which the osmotic laxative magnesium sulphate increases the intestinal aquaporin 3 expression in HT-29 cells ' () 88 Life Sciences : 194 -200.
Jeong, D., Kim, D.H., Kang, I.B., Kim, H., Kim, H.S., Seo, K.H. and Song, K.Y., 2017. Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1. Food and Function 8: 680-686.
'Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1 ' () 8 Food and Function : 680 -686.
Joossens, M., Huys, G., Cnockaert, M., De Preter, V., Verbeke, K., Rutgeerts, P., Vandamme, P. and Vermeire, S., 2011. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60: 631-637.
'Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives ' () 60 Gut : 631 -637.
Jun, J.Y., Choi, S., Yeum, C.H., Chang, I.Y., You, H.J., Park, C.K., Kim, M.Y., Kong, I.D., Kim, M.J., Lee, K.P., So, I. and Kim, K.W., 2004. Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. European Journal of Pharmacology 495: 35-42.
'Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine ' () 495 European Journal of Pharmacology : 35 -42.
Khalif, I.L., Quigley, E.M., Konovitch, E.A. and Maximova, I.D., 2005. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 37: 838-849.
'Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation ' () 37 Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver : 838 -849.
Kim, S.E., Choi, S.C., Park, K.S., Park, M.I., Shin, J.E., Lee, T.H., Jung, K.W., Koo, H.S. and Myung, S.J., 2015. Change of fecal flora and effectiveness of the short-term VSL#3 probiotic treatment in patients with functional constipation. Journal of Neurogastroenterology and Motility 21: 111-120.
'Change of fecal flora and effectiveness of the short-term VSL#3 probiotic treatment in patients with functional constipation ' () 21 Journal of Neurogastroenterology and Motility : 111 -120.
King, L.S., Kozono, D. and Agre, P., 2004. From structure to disease: the evolving tale of aquaporin biology. Nature reviews. Molecular Cell Biology 5: 687-698.
'From structure to disease: the evolving tale of aquaporin biology ' () 5 Molecular Cell Biology : 687 -698.
Koh, S.D., Sanders, K.M. and Ward, S.M., 1998. Spontaneous electrical rhythmicity in cultured interstitial cells of cajal from the murine small intestine. Journal of Physiology 513(1): 203-213.
'Spontaneous electrical rhythmicity in cultured interstitial cells of cajal from the murine small intestine ' () 513 Journal of Physiology : 203 -213.
Kon, R., Ikarashi, N., Hayakawa, A., Haga, Y., Fueki, A., Kusunoki, Y., Tajima, M., Ochiai, W., Machida, Y. and Sugiyama, K., 2015. Morphine-induced constipation develops with increased aquaporin-3 expression in the colon via increased serotonin secretion. Toxicological Sciences 145: 337-347.
'Morphine-induced constipation develops with increased aquaporin-3 expression in the colon via increased serotonin secretion ' () 145 Toxicological Sciences : 337 -347.
Kunde, D.A., Crawford, A. and Geraghty, D.P., 2013. Tachykinin (NK1, NK2 and NK3) receptor, transient receptor potential vanilloid 1 (TRPV1) and early transcription factor, cFOS, mRNA expression in rat tissues following systemic capsaicin treatment. Regulatory Peptides 183: 35-41.
'Tachykinin (NK1, NK2 and NK3) receptor, transient receptor potential vanilloid 1 (TRPV1) and early transcription factor, cFOS, mRNA expression in rat tissues following systemic capsaicin treatment ' () 183 Regulatory Peptides : 35 -41.
Lakhan, S.E. and Kirchgessner, A., 2010. Neuroinflammation in inflammatory bowel disease. Journal of Neuroinflammation 7: 37.
'Neuroinflammation in inflammatory bowel disease ' () 7 Journal of Neuroinflammation : 37.
Latorre, E., Layunta, E., Grasa, L., Castro, M., Pardo, J., Gomollon, F., Alcalde, A.I. and Mesonero, J.E., 2016. Intestinal serotonin transporter inhibition by toll-like receptor 2 activation. A feedback modulation. PLoS ONE 11: e0169303.
'Intestinal serotonin transporter inhibition by toll-like receptor 2 activation ' () 11 PLoS ONE : e0169303.
Li, C., Nie, S.P., Zhu, K.X., Xiong, T., Li, C., Gong, J. and Xie, M.Y., 2015. Effect of Lactobacillus plantarum NCU116 on loperamide-induced constipation in mice. International Journal of Food Sciences and Nutrition 66: 533-538.
'Effect of Lactobacillus plantarum NCU116 on loperamide-induced constipation in mice ' () 66 International Journal of Food Sciences and Nutrition : 533 -538.
Pryde, S.E., Duncan, S.H., Hold, G.L., Stewart, C.S. and Flint, H.J., 2002. The microbiology of butyrate formation in the human colon. FEMS Microbiology Letters 217: 133-139.
'The microbiology of butyrate formation in the human colon ' () 217 FEMS Microbiology Letters : 133 -139.
Reigstad, C.S., Salmonson, C.E., Rainey 3rd, J.F., Szurszewski, J.H., Linden, D.R., Sonnenburg, J.L., Farrugia, G. and Kashyap, P.C., 2015. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB Journal 29: 1395-1403.
'Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells ' () 29 FASEB Journal : 1395 -1403.
Sanders, K.M., 1996. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 111: 492-515.
'A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract ' () 111 Gastroenterology : 492 -515.
Sanders, K.M. and Ward, S.M., 2007. Kit mutants and gastrointestinal physiology. Journal of Physiology 578: 33-42.
'Kit mutants and gastrointestinal physiology ' () 578 Journal of Physiology : 33 -42.
Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermudez-Humaran, L.G., Gratadoux, J.J., Blugeon, S., Bridonneau, C., Furet, J.P., Corthier, G., Grangette, C., Vasquez, N., Pochart, P., Trugnan, G., Thomas, G., Blottiere, H.M., Dore, J., Marteau, P., Seksik, P. and Langella, P., 2008. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences of the USA 105: 16731-16736.
'Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients ' () 105 Proceedings of the National Academy of Sciences of the USA : 16731 -16736.
Suares, N.C. and Ford, A.C., 2011. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. American Journal of Gastroenterology 106: 1582-1591.
'Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis ' () 106 American Journal of Gastroenterology : 1582 -1591.
Suo, H., Zhao, X., Qian, Y., Li, G., Liu, Z., Xie, J. and Li, J., 2014. Therapeutic effect of activated carbon-induced constipation mice with Lactobacillus fermentum Suo on treatment. International Journal of Molecular Sciences 15: 21875-21895.
'Therapeutic effect of activated carbon-induced constipation mice with Lactobacillus fermentum Suo on treatment ' () 15 International Journal of Molecular Sciences : 21875 -21895.
Takaki, M., 2003. Gut pacemaker cells: the interstitial cells of Cajal (ICC). Journal of Smooth Muscle Research (Nihon Heikatsukin Gakkai kikanshi) 39: 137-161.
'Gut pacemaker cells: the interstitial cells of Cajal (ICC) ' () 39 Journal of Smooth Muscle Research (Nihon Heikatsukin Gakkai kikanshi) : 137 -161.
Tong, W.D., Liu, B.H., Zhang, L.Y., Xiong, R.P., Liu, P. and Zhang, S.B., 2005. Expression of c-kit messenger ribonucleic acid and c-kit protein in sigmoid colon of patients with slow transit constipation. International Journal of Colorectal Disease 20: 363-367.
'Expression of c-kit messenger ribonucleic acid and c-kit protein in sigmoid colon of patients with slow transit constipation ' () 20 International Journal of Colorectal Disease : 363 -367.
Utsumi, D., Matsumoto, K., Amagase, K., Horie, S. and Kato, S., 2016. 5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis. British Journal of Pharmacology 173: 1835-1849.
'5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis ' () 173 British Journal of Pharmacology : 1835 -1849.
Wang, H., Gong, J., Wang, W., Long, Y., Fu, X., Fu, Y., Qian, W. and Hou, X., 2014. Are there any different effects of Bifidobacterium, Lactobacillus and Streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model? PLoS ONE 9: e90153.
'Are there any different effects of Bifidobacterium, Lactobacillus and Streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model? ' () 9 PLoS ONE : e90153.
Wang, L., Hu, L., Xu, Q., Yin, B., Fang, D., Wang, G., Zhao, J., Zhang, H. and Chen, W., 2017. Bifidobacterium adolescentis exerts strain-specific effects on constipation induced by loperamide in BALB/c mice. International Journal of Molecular Sciences 18: 318.
'Bifidobacterium adolescentis exerts strain-specific effects on constipation induced by loperamide in BALB/c mice ' () 18 International Journal of Molecular Sciences : 318.
Watson, S.P. and Downes, C.P., 1983. Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus. European Journal of Pharmacology 93: 245-253.
'Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus ' () 93 European Journal of Pharmacology : 245 -253.
Wojtyniak, K., Horvath, A., Dziechciarz, P. and Szajewska, H., 2017. Lactobacillus casei rhamnosus Lcr35 in the management of functional constipation in children: a randomized trial. Journal of Pediatrics 184: 101-105.
'Lactobacillus casei rhamnosus Lcr35 in the management of functional constipation in children: a randomized trial ' () 184 Journal of Pediatrics : 101 -105.
Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., Ann, P., Ma, L., Nagler, C.R., Ismagilov, R.F., Mazmanian, S.K. and Hsiao, E.Y., 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161: 264-276.
'Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis ' () 161 Cell : 264 -276.
Yu, T., Zheng, Y.P., Tan, J.C., Xiong, W.J., Wang, Y. and Lin, L., 2017. Effects of prebiotics and synbiotics on functional constipation. American Journal of the Medical Sciences 353: 282-292.
'Effects of prebiotics and synbiotics on functional constipation ' () 353 American Journal of the Medical Sciences : 282 -292.
Zhao, X., Suo, H.Y., Qian, Y., Li, G.J., Liu, Z.H. and Li, J., 2015. Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice. Molecular Medicine Reports 12: 3191-3199.
'Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice ' () 12 Molecular Medicine Reports : 3191 -3199.
Zhi, H. and Yuan, W.T., 2011. Expression of aquaporin 3, 4, and 8 in colonic mucosa of rat models with slow transit constipation. Chinese Journal of Gastrointestinal Surgery (Zhonghua Wei Chang Wai Ke Za Zhi) 14: 459-461.
'Expression of aquaporin 3, 4, and 8 in colonic mucosa of rat models with slow transit constipation ' () 14 Chinese Journal of Gastrointestinal Surgery (Zhonghua Wei Chang Wai Ke Za Zhi) : 459 -461.
Zhu, L., Liu, W., Alkhouri, R., Baker, R.D., Bard, J.E., Quigley, E.M. and Baker, S.S., 2014. Structural changes in the gut microbiome of constipated patients. Physiological Genomics 46: 679-686.
'Structural changes in the gut microbiome of constipated patients ' () 46 Physiological Genomics : 679 -686.
Zhu, S., Ran, J., Yang, B. and Mei, Z., 2017. Aquaporins in digestive system. Advances in Experimental Medicine and Biology 969: 123-130.
'Aquaporins in digestive system ' () 969 Advances in Experimental Medicine and Biology : 123 -130.
Zoppi, G., Cinquetti, M., Luciano, A., Benini, A., Muner, A. and Bertazzoni Minelli, E., 1998. The intestinal ecosystem in chronic functional constipation. Acta Paediatrica 87: 836-841.
'The intestinal ecosystem in chronic functional constipation ' () 87 Acta Paediatrica : 836 -841.
All Time | Past 365 days | Past 30 Days | |
---|---|---|---|
Abstract Views | 0 | 0 | 0 |
Full Text Views | 306 | 245 | 52 |
PDF Views & Downloads | 169 | 133 | 32 |
Constipation has a significant influence on quality of life. Patients with constipation have slow waves in their gastrointestinal smooth muscles and less faecal water contents, which are closely associated with down-regulation of the interstitial cells of Cajal (ICC) in the gastrointestinal muscles and the aquaporin protein AQP3 expressed in colon epithelial cells. Recent studies supported that patients with constipation have altered intestinal microbial structures compared with healthy controls. Intestinal dysbiosis might be one possible pathophysiological mechanism causing constipation. Bacterial strains, such as Lactobacillus spp., have shown many beneficial effects on the amelioration of constipation. However, few studies reported the structural changes of intestinal microbiota post-intervention of probiotics. In this study, a bacterial mixture was administrated to rats with loperamide-induced constipation. Effects of the bacterial mixture on small intestine transit (SIT), faecal water content, and the intestinal microbiome in rats were evaluated. Meanwhile, we investigated several factors involved in signalling pathways that regulate function of ICC and expression of AQP3 to discuss the possible underlying molecular mechanisms. Intervention of the bacterial mixture improved SIT and faecal water content in constipated rats. The up-regulation of C-kit/SP signalling pathways in ICC and AQP3 significantly contributed to improvements. These changes were closely associated with the manipulation of intestinal dysbiosis in constipated rats. Furthermore, our results revealed the important role of intestinal microbiota in affecting gut motility through regulation of serotonin biosynthesis. This monoamine neurotransmitter, secreted from enterochromaffin cells, up-regulated both substance P/neurokinin 1 receptors pathway of ICC and the expression of AQP3 in intestinal epithelial cells. Our study suggested that the disrupted microbiome in patients could be a potential therapeutic target for the improvement of constipation.
All Time | Past 365 days | Past 30 Days | |
---|---|---|---|
Abstract Views | 0 | 0 | 0 |
Full Text Views | 306 | 245 | 52 |
PDF Views & Downloads | 169 | 133 | 32 |