1.Mearin, F, Lacy, BE, Chang, L et al. (2016) Bowel disorders. Gastroenterology 150, 1393–1407.
2.Suares, NC & Ford, AC (2011) Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol 106, 1582–1591.
3.Dimidi, E, Cox, C, Grant, R et al. (2019) Perceptions of constipation among the general public and people with constipation differ strikingly from those of general and specialist doctors and the Rome IV criteria. Am J Gastroenterol ().
4.Dimidi, E, Dibley, L, Cotterill, N et al. (2016) Validated constipation symptom and quality-of-life measures neither reflect patient and clinician concerns nor use words familiar to patients. Gastrointest Nurs 14, 29–38.
5.Wald, A, Scarpignato, C, Kamm, MA et al. (2007) The burden of constipation on quality of life: results of a multinational survey. Aliment Pharmacol Ther 26, 227–236.
6.Sun, SX, Dibonaventura, M, Purayidathil, FW et al. (2011) Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey. Dig Dis Sci 56, 2688–2695.
7.Nellesen, D, Yee, K, Chawla, A et al. (2013) A systematic review of the economic and humanistic burden of illness in irritable bowel syndrome and chronic constipation. J Manag Care Pharm 19, 755–764.
9.Shafe, AC, Lee, S, Dalrymple, JS et al. (2011) The LUCK study: Laxative Usage in patients with GP-diagnosed Constipation in the UK, within the general population and in pregnancy. An epidemiological study using the General Practice Research Database (GPRD). Therap Adv Gastroenterol 4, 343–363.
10.Guerin, A, Carson, RT, Lewis, B et al. (2014) The economic burden of treatment failure amongst patients with irritable bowel syndrome with constipation or chronic constipation: a retrospective analysis of a Medicaid population. J Med Econ 17, 577–586.
11.Christodoulides, S, Dimidi, E, Fragkos, KC et al. (2016) Systematic review with meta-analysis: effect of fibre supplementation on chronic idiopathic constipation in adults. Aliment Pharmacol Ther 44, 103–116.
12.Bharucha, AE, Pemberton, JH & Locke, GR 3rd. (2013) American Gastroenterological Association technical review on constipation. Gastroenterology 144, 218–238.
13.Johanson, JF & Kralstein, J (2007) Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther 25, 599–608.
14.Emmanuel, A, Quigley, EM, Simren, M et al. (2013) Factors affecting satisfaction with treatment in European women with chronic constipation: An internet survey. United European Gastroenterol J 1, 375–384.
15.Hill, C, Guarner, F, Reid, G et al. (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11, 506–514.
16.Dimidi, E, Christodoulides, S, Scott, SM et al. (2017) Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Adv Nutr 8, 484–494.
17.Chassard, C, Dapoigny, M, Scott, KP et al. (2012) Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther 35, 828–838.
18.Parthasarathy, G, Chen, J, Chen, X et al. (2016) Relationship between microbiota of the colonic mucosa vs feces and symptoms, colonic transit, and methane production in female patients with chronic constipation. Gastroenterology 150, 367–379.
19.Ishizuka, A, Tomizuka, K, Aoki, R et al. (2012) Effects of administration of Bifidobacterium animalis subsp. lactis GCL2505 on defecation frequency and bifidobacterial microbiota composition in humans. J Biosci Bioeng 113, 587–591.
20.Kim, SE, Choi, SC, Park, KS et al. (2015) Change of fecal flora and effectiveness of the short-term VSL#3 probiotic treatment in patients with functional constipation. J Neurogastroenterol Motil 21, 111–120.
21.Matsumoto, K, Takada, T, Shimizu, K et al. (2006) The effects of a probiotic milk product containing Lactobacillus casei strain Shirota on the defecation frequency and the intestinal microflora of sub-optimal health state volunteers: a randomized placebo-controlled cross-over study. Biosci Microflora 25, 39–48.
22.Dimidi, E, Zdanaviciene, A, Christodoulides, S et al. (2019) Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation. Aliment Pharmacol Ther 49, 251–264.
23.Morrison, DJ & Preston, T (2016) Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7, 189–200.
24.Yajima, T (1985) Contractile effect of short-chain fatty acids on the isolated colon of the rat. J Physiol 368, 667–678.
25.Cherbut, C, Aube, AC, Blottiere, HM et al. (1996) In vitro contractile effects of short chain fatty acids in the rat terminal ileum. Gut 38, 53–58.
26.Rondeau, MP, Meltzer, K, Michel, KE et al. (2003) Short chain fatty acids stimulate feline colonic smooth muscle contraction. J Feline Med Surg 5, 167–173.
27.Fukumoto, S, Tatewaki, M, Yamada, T et al. (2003) Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 284, R1269–R1276.
28.Liu, ZM, Xu, ZY, Han, M et al. (2015) Efficacy of pasteurised yoghurt in improving chronic constipation: A randomised, double-blind, placebo-controlled trial. Int Dairy J 40, 1–5.
29.Spanhaak, S, Havenaar, R & Schaafsma, G (1998) The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans. Eur J Clin Nutr 52, 899–907.
30.Valerio, F, Russo, F, de Candia, S et al. (2010) Effects of Probiotic Lactobacillus paracasei-enriched artichokes on constipated patients: a pilot study. J Clin Gastroenterol 44, S49–S53.
31.Riezzo, G, Orlando, A, D'Attoma, B et al. (2012) Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation – a double-blind, controlled, crossover study. Aliment Pharmacol Ther 35, 441–450.
32.Sakai, T, Makino, H, Ishikawa, E et al. (2011) Fermented milk containing Lactobacillus casei strain Shirota reduces incidence of hard or lumpy stools in healthy population. Int J Food Sci Nutr 62, 423–430.
33.Marsono, Y, Illman, RJ, Clarke, JM et al. (1993) Plasma lipids and large bowel volatile fatty acids in pigs fed on white rice, brown rice and rice bran. Br J Nutr 70, 503–513.
34.Matsuo, K, Ota, H, Akamatsu, T et al. (1997) Histochemistry of the surface mucous gel layer of the human colon. Gut 40, 782–789.
35.Snape, WJ Jr., Shiff, S & Cohen, S (1980) Effect of deoxycholic acid on colonic motility in the rabbit. Am J Physiol 238, G321–G325.
36.Keely, SJ, Scharl, MM, Bertelsen, LS et al. (2007) Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships. Am J Physiol Gastrointest Liver Physiol 292, G290–G297.
37.Caballero-Franco, C, Keller, K, De Simone, C et al. (2007) The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 292, G315–G322.
38.Ouwehand, AC, Lagstrom, H, Suomalainen, T et al. (2002) Effect of probiotics on constipation, fecal azoreductase activity and fecal mucin content in the elderly. Ann Nutr Metab 46, 159–162.
39.Marteau, P, Cuillerier, E, Meance, S et al. (2002) Bifidobacterium animalis strain DN-173 010 shortens the colonic transit time in healthy women: a double-blind, randomized, controlled study. Aliment Pharmacol Ther 16, 587–593.
40.Tillisch, K, Labus, J, Kilpatrick, L et al. (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144, 1394–1401.
41.Kunze, WA, Mao, YK, Wang, B et al. (2009) Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J Cell Mol Med 13, 2261–2270.
42.Wang, B, Mao, YK, Diorio, C et al. (2010) Lactobacillus reuteri ingestion and IK(Ca) channel blockade have similar effects on rat colon motility and myenteric neurones. Neurogastroenterol Motil 22, 98–107.
43.Khalif, IL, Quigley, EM, Konovitch, EA et al. (2005) Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig Liver Dis 37, 838–849.
44.Collins, SM (1996) The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterology 111, 1683–1699.
45.Guarino, MP, Altomare, A, Stasi, E et al. (2008) Effect of acute mucosal exposure to Lactobacillus rhamnosus GG on human colonic smooth muscle cells. J Clin Gastroenterol 42(Suppl 3 ), S185–S190.
46.Isolauri, E, Sutas, Y, Kankaanpaa, P et al. (2001) Probiotics: effects on immunity. Am J Clin Nutr 73(2 Suppl), 444S–450S.
47.Ibnou-Zekri, N, Blum, S, Schiffrin, EJ et al. (2003) Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro. Infect Immun 71, 428–436.
48.Arunachalam, K, Gill, HS & Chandra, RK (2000) Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019). Eur J Clin Nutr 54, 263–267.
49.Yang, YX, He, M, Hu, G et al. (2008) Effect of a fermented milk containing Bifidobacterium lactis DN-173010 on Chinese constipated women. World J Gastroenterol 14, 6237–6243.
50.Waller, PA, Gopal, PK, Leyer, GJ et al. (2011) Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults. Scand J Gastroenterol 46, 1057–1064.
51.Ibarra, A, Latreille-Barbier, M, Donazzolo, Y et al. (2018) Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: a double-blind, randomized, placebo-controlled, and dose-ranging trial. Gut Microbes 9, 236–251.
52.Ojetti, V, Ianiro, G, Tortora, A et al. (2014) The effect of Lactobacillus reuteri supplementation in adults with chronic functional constipation: a randomized, double-blind, placebo-controlled trial. J Gastrointestin Liver Dis 23, 387–391.
53.Koebnick, C, Wagner, I, Leitzmann, P et al. (2003) Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation. Can J Gastroenterol 17, 655–659.
54.Mazlyn, MM, Nagarajah, LH, Fatimah, A et al. (2013) Effects of a probiotic fermented milk on functional constipation: a randomized, double-blind, placebo-controlled study. J Gastroenterol Hepatol 28, 1141–1147.
55.Del Piano, M, Carmagnola, S, Anderloni, A et al. (2010) The use of probiotics in healthy volunteers with evacuation disorders and hard Stools. A double-blind, randomized, placebo-controlled study. J Clin Gastroenterol 44, S30–SS4.
56.Chmielewska, A & Szajewska, H (2010) Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol 16, 69–75.
57.Miller, LE, Zimmermann, AK & Ouwehand, AC (2016) Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit. World J Gastroenterol 22, 5122–5131.
58.Miller, LE, Ouwehand, AC & Ibarra, A (2017) Effects of probiotic-containing products on stool frequency and intestinal transit in constipated adults: systematic review and meta-analysis of randomized controlled trials. Ann Gastroenterol 30, 629–639.
59.Miller, LE & Ouwehand, AC (2013) Probiotic supplementation decreases intestinal transit time: meta-analysis of randomized controlled trials. World J Gastroenterol 19, 4718–4725.
60.Ford, AC, Quigley, EM, Lacy, BE et al. (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109, 1547–1561.
61.Dimidi, E, Christodoulides, S, Fragkos, KC et al. (2014) The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 100, 1075–1084.
62.Whelan, K (2014) Editorial: The importance of systematic reviews and meta-analyses of probiotics and prebiotics. Am J Gastroenterol 109, 1563–1565.
63.Hung, A, Kang, N, Bollom, A et al. (2015) Complementary and alternative medicine use is prevalent among patients with gastrointestinal diseases. Dig Dis Sci 60, 1883–1888.
64.Dimidi, E, Cox, C, Scott, SM et al. (2019) Probiotic use is common in constipation, but only a minority of general and specialist doctors recommend them and consider there to be an evidence base. Nutrition 61, 157–163.
65.Cheng, C, Chan, AO, Hui, WM et al. (2003) Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study. Aliment Pharmacol Ther 18, 319–326.
66.Cordina, C, Shaikh, I, Shrestha, S et al. (2011) Probiotics in the management of gastrointestinal disease: analysis of the attitudes and prescribing practices of gastroenterologists and surgeons. J Dig Dis 12, 489–496.
67.Jordan, D, Johnson, N & Thomas, L (2015) Probiotics in primary care: a survey of health professionals. Practice Nursing 26, 550–554.
68.Hedin, CR, Mullard, M, Sharratt, E et al. (2010) Probiotic and prebiotic use in patients with inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 16, 2099–2108.
69.He, M, Hu, G & Yang, Y (2009) Effect of probiotic yogurt containing Bifidobacterium animalis strain DN-173010 on symptoms of constipation. Chin J Gastroenterol 14, 287–289.
70.Krammer, H, von Seggern, H, Schaumburg, J et al. (2011) Effect of Lactobacillus casei Shirota on colonic transit time in patients with chronic constipation. Coloproctology 33, 109–113.
71.Kieffer, DA, Martin, RJ & Adams, SH (2016) Impact of dietary fibers on nutrient management and detoxification organs: gut, liver, and kidneys. Adv Nutr 7, 1111–1121.
72.Yano, JM, Yu, K, Donaldson, GP et al. (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276.
73.Triantafyllou, K, Chang, C & Pimentel, M (2014) Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil 20, 31–40.
74.Collins, SM & Bercik, P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136, 2003–2014.
75.Ng, SC, Benjamin, JL, McCarthy, NE et al. (2011) Relationship between human intestinal dendritic cells, gut microbiota, and disease activity in Crohn's disease. Inflamm Bowel Dis 17, 2027–2037.
76.Brun, P, Giron, MC, Qesari, M et al. (2013) Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145, 1323–1333.