The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

Gut Microbes

Volumn 4, Issue 1, 2013, Pages

  Saulnier, Delphine M ^a   Ringel, Yehuda ^b   Heyman, Melvin B ^c   Foster, Jane A ^d,e   Bercik, Premysl ^d,e   Shulman, Robert J ^f   Versalovic, James ^f,g   Verdu, Elena ^d   Dinan, Ted G ^h   Hecht, Gail ⁱ   Guarner, Francisco ^j  

^a NIZO FOOD RESEARCH   (Netherlands)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d MCMASTER UNIVERSITY   (Canada)

^e MCMASTER UNIVERSITY   (Canada)

^f BAYLOR COLLEGE OF MEDICINE   (United States)

^g TEXAS CHILDREN S HOSPITAL   (United States)

^h UNIVERSITY COLLEGE CORK   (Ireland)

ⁱ UNIVERSITY OF ILLINOIS   (United States)

^j HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

more..

Author keywords

Biomarkers; Gastrointestinal tract; Human trials; Immune; Microbiome; Microbiota; Neurogastroenterology; Prebiotic; Probiotic

Indexed keywords

4 AMINOBUTYRIC ACID; ACETYLCHOLINE; BRAIN DERIVED NEUROTROPHIC FACTOR; CALBINDIN; CARBOHYDRATE; CLAUDIN; CLAUDIN 2; CORTICOSTERONE; CORTICOTROPIN; CYTOKINE; FRUCTAN; GALACTOSE OLIGOSACCHARIDE; IMMUNOGLOBULIN A; INULIN; JUNCTIONAL ADHESION MOLECULE; MYOSIN LIGHT CHAIN KINASE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; NORADRENALIN; OCCLUDIN; PLACEBO; PREBIOTIC AGENT; PROBIOTIC AGENT; PROTEIN ZO2; SEROTONIN; TUMOR NECROSIS FACTOR ALPHA; GASTROINTESTINAL AGENT;

ABDOMINAL PAIN; ANXIETY; AUTISM; AUTONOMIC NERVOUS SYSTEM; BEHAVIOR; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL (TOPIC); COMORBIDITY; CONTROLLED CLINICAL TRIAL (TOPIC); GAMMAPROTEOBACTERIA; GASTROINTESTINAL DISEASE; HAEMOPHILUS PARAINFLUENZAE; HUMAN; HYPERALGESIA; HYPERSENSITIVITY; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; IMMUNE RESPONSE; IMMUNOFLUORESCENCE TEST; INTESTINE FLORA; INTESTINE INNERVATION; IRRITABLE COLON; LACTOBACILLUS ACIDOPHILUS; MEMORY DISORDER; MENTAL DISEASE; MICROBIOME; NONHUMAN; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STRESS; BIOMARKERS; EMOTION; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRACT; HUMAN TRIALS; IMMUNE; METAGENOME; MICROBIOLOGY; MICROFLORA; NEUROGASTROENTEROLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALIA; MAMMALIA;

BIOMARKERS; GASTROINTESTINAL TRACT; HUMAN TRIALS; IMMUNE; MICROBIOME; MICROBIOTA; NEUROGASTROENTEROLOGY; PREBIOTIC; PROBIOTIC;

BEHAVIOR; CENTRAL NERVOUS SYSTEM; EMOTIONS; ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL AGENTS; GASTROINTESTINAL DISEASES; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRACT; HUMANS; METAGENOME; PREBIOTICS; PROBIOTICS;

EID: 84871776844     PISSN: 19490976     EISSN: 19490984     Source Type: Journal    
DOI: 10.4161/gmic.22973     Document Type: Review

References (89)

1. O'Mahony SM, Hyland NP, Dinan TG, Cryan JF. Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology (Berl) 2011; 214:71-88; PMID:20886335; http://dx.doi.org/10.1007/s00213-010-2010-9.
2. O'Hara AM, Shanahan F. Gut microbiota: mining for therapeutic potential. Clin Gastroenterol Hepatol 2007; 5:274-84; PMID:17368226; http://dx.doi. org/10.1016/j.cgh.2006.12.009.
3. Bercik P, Collins SM, Verdu EF. Microbes and the gutbrain axis. Neurogastroenterol Motil 2012; 24:405-13; PMID:22404222; http://dx.doi.org/10.1111/j.1365-2982.2012.01906.x.
4. Grenham S, Clarke G, Cryan JF, Dinan TG. Brain-gutmicrobe communication in health and disease. Front Physiol 2011; 2:94; PMID:22162969.
5. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9:799-809; PMID:19855405; http://dx.doi.org/10.1038/nri2653.
6. Tlaskalová-Hogenová H, Stěpánková R, Kozáková H, Hudcovic T, Vannucci L, Tučková L, et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol 2011; 8:110-20; PMID:21278760; http://dx.doi.org/10.1038/cmi.2010.67.
7. Yan F, Polk DB. Probiotics and immune health. Curr Opin Gastroenterol 2011; 27:496-501; PMID:21897224; http://dx.doi.org/10.1097/MOG.0b013e32834baa4d.
8. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 2011; 141:769-76; PMID:21430248; http://dx.doi.org/10.3945/jn.110.135657.
9. Mennigen R, Nolte K, Rijcken E, Utech M, Loeffler B, Senninger N, et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 2009; 296:G1140-9; PMID:19221015; http://dx.doi.org/10.1152/ajpgi.90534.2008.
10. Natividad JM, Petit V, Huang X, de Palma G, Jury J, Sanz Y, et al. Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1(-/-);Nod2(-/-) Mice. Inflamm Bowel Dis 2011; PMID:22162005.
11. Yan F, Cao H, Cover TL, Washington MK, Shi Y, Liu L, et al. Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J Clin Invest 2011; 121:2242-53; PMID:21606592; http://dx.doi.org/10.1172/JCI44031.
12. Raheja G, Singh V, Ma K, Boumendjel R, Borthakur A, Gill RK, et al. Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism. Am J Physiol Gastrointest Liver Physiol 2010; 298:G395-401; PMID:20044511; http://dx.doi. org/10.1152/ajpgi.00465.2009.
13. Borthakur A, Gill RK, Tyagi S, Koutsouris A, Alrefai WA, Hecht GA, et al. The probiotic Lactobacillus acidophilus stimulates chloride/hydroxyl exchange activity in human intestinal epithelial cells. J Nutr 2008; 138:1355-9; PMID:18567760.
14. Kamm K, Hoppe S, Breves G, Schröder B, Schemann M. Effects of the probiotic yeast Saccharomyces boulardii on the neurochemistry of myenteric neurones in pig jejunum. Neurogastroenterol Motil 2004; 16:53-60; PMID:14764205; http://dx.doi.org/10.1046/j.1365-2982.2003.00458.x.
15. Fung C, Ellis M, Bornstein JC. Luminal Cholera Toxin Alters Motility in Isolated Guinea-Pig Jejunum via a Pathway Independent of 5-HT(3) Receptors. Front Neurosci 2010; 4:162; PMID:21048896; http://dx.doi.org/10.3389/fnins.2010.00162.
16. Kamiya T, Wang L, Forsythe P, Goettsche G, Mao Y, Wang Y, et al. Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague-Dawley rats. Gut 2006; 55:191-6; PMID:16361309; http://dx.doi.org/10.1136/gut.2005.070987.
17. Rousseaux C, Thuru X, Gelot A, Barnich N, Neut C, Dubuquoy L, et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med 2007; 13:35-7; PMID:17159985; http://dx.doi.org/10.1038/nm1521.
18. Ait-Belgnaoui A, Han W, Lamine F, Eutamene H, Fioramonti J, Bueno L, et al. Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction. Gut 2006; 55:1090-4; PMID:16507583; http://dx.doi. org/10.1136/gut.2005.084194.
19. Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gutbrain communication. Neurogastroenterol Motil 2011; 23:1132-9; PMID:21988661; http://dx.doi. org/10.1111/j.1365-2982.2011.01796.x.
20. Verdú EF, Bercík P, Bergonzelli GE, Huang XX, Blennerhasset P, Rochat F, et al. Lactobacillus paracasei normalizes muscle hypercontractility in a murine model of postinfective gut dysfunction. Gastroenterology 2004; 127:826-37; PMID:15362038; http://dx.doi. org/10.1053/j.gastro.2004.06.007.
21. Eutamene H, Lamine F, Chabo C, Theodorou V, Rochat F, Bergonzelli GE, et al. Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats. J Nutr 2007; 137:1901-7; PMID:17634262.
22. Duncker SC, Kamiya T, Wang L, Yang P, Bienenstock J. Probiotic Lactobacillus reuteri alleviates the response to gastric distension in rats. J Nutr 2011; 141:1813-8; PMID:21880952; http://dx.doi.org/10.3945/jn.110.136689.
23. Azpiroz F. Intestinal perception: mechanisms and assessment. Br J Nutr 2005; 93(Suppl 1):S7-12; PMID:15877899; http://dx.doi.org/10.1079/BJN20041338.
24. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 2010; 170:1179-88; PMID:20696216; http://dx.doi.org/10.1016/j.neuroscience.2010.08.005.
25. Clarke G, Fitzgerald P, Hennessy AA, Cassidy EM, Quigley EM, Ross P, et al. Marked elevations in proinflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome. J Lipid Res 2010; 51:1186-92; PMID:19965606; http://dx.doi. org/10.1194/jlr.P000695.
26. Wall R, Ross RP, Shanahan F, O'Mahony L, Kiely B, Quigley E, et al. Impact of administered bifidobacterium on murine host fatty acid composition. Lipids 2010; 45:429-36; PMID:20405232; http://dx.doi. org/10.1007/s11745-010-3410-7.
27. Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 2011; 23:255-64, e119; PMID:21054680; http://dx.doi.org/10.1111/j.1365-2982.2010.01620.x.
28. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 2011; 108:3047-52; PMID:21282636; http://dx.doi.org/10.1073/pnas.1010529108.
29. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 2004; 558:263-75; PMID:15133062; http://dx.doi.org/10.1113/jphysiol. 2004.063388.
30. Cushman J, Lo J, Huang Z, Wasserfall C, Petitto JM. Neurobehavioral changes resulting from recombinase activation gene 1 deletion. Clin Diagn Lab Immunol 2003; 10:13-8; PMID:12522033.
31. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011; 108:16050-5; PMID:21876150; http://dx.doi.org/10.1073/pnas.1102999108.
32. Lyte M. The role of microbial endocrinology in infectious disease. J Endocrinol 1993; 137:343-5; PMID:8371072; http://dx.doi.org/10.1677/joe.0.1370343.
33. Bailey MT, Lubach GR, Coe CL. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr 2004; 38:414-21; PMID:15085020; http://dx.doi. org/10.1097/00005176-200404000-00009.
34. Guthrie GD, Nicholson-Guthrie CS. gamma-Aminobutyric acid uptake by a bacterial system with neurotransmitter binding characteristics. Proc Natl Acad Sci U S A 1989; 86:7378-81; PMID:2552441; http://dx.doi.org/10.1073/pnas.86.19.7378.
35. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011; 105:755-64; PMID:20974015; http://dx.doi.org/10.1017/S0007114510004319.
36. Lyte M, Li W, Opitz N, Gaykema RP, Goehler LE. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiol Behav 2006; 89:350-7; PMID:16887154; http://dx.doi.org/10.1016/j.physbeh.2006.06.019.
37. Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, et al. Bacterial infection causes stress-induced memory dysfunction in mice. Gut 2011; 60:307-17; PMID:20966022; http://dx.doi. org/10.1136/gut.2009.202515.
38. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun 2010; 24:9-16; PMID:19481599; http://dx.doi. org/10.1016/j.bbi.2009.05.058.
39. Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2011; 2:256-61; PMID:21983070; http://dx.doi.org/10.4161/gmic.2.4.16108.
40. Association AP. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC, 2000.
41. Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol 2011; 11:22; PMID:21410934; http://dx.doi.org/10.1186/1471-230X-11-22.
42. Williams BL, Hornig M, Parekh T, Lipkin WI. Application of novel PCR-based methods for detection, quantitation and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio 2012; 3; PMID:22233678; http://dx.doi. org/10.1128/mBio.00261-11.
43. Williams BL, Hornig M, Buie T, Bauman ML, Cho Paik M, Wick I, et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 2011; 6:e24585; PMID:21949732; http://dx.doi.org/10.1371/journal.pone.0024585.
44. Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004; 70:6459-65; PMID:15528506; http://dx.doi.org/10.1128/AEM.70.11.6459-6465.2004.
45. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 2005; 54:987-91; PMID:16157555; http://dx.doi.org/10.1099/jmm.0.46101-0.
46. Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 2002; 35(Suppl 1):S6-16; PMID:12173102; http://dx.doi. org/10.1086/341914.
47. Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 2010; 16:444-53; PMID:20603222; http://dx.doi.org/10.1016/j.anaerobe.2010.06.008.
48. Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK. Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res 2010; 9:2996-3004; PMID:20337404; http://dx.doi. org/10.1021/pr901188e.
49. MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, et al. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res 2007; 176:149-69; PMID:16950524; http://dx.doi.org/10.1016/j.bbr.2006.07.025.
50. Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 2000; 15:429-35; PMID:10921511; http://dx.doi.org/10.1177/088307380001500701.
51. Kałużna-Czaplińska J, Błaszczyk S. The level of arabinitol in autistic children after probiotic therapy. Nutrition 2012; 28:124-6; PMID:22079796; http://dx.doi.org/10.1016/j.nut.2011.08.002.
52. Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011; 2011:161358; PMID:22114588; http://dx.doi. org/10.1155/2011/161358.
53. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006; 130:1377-90; PMID:16678553; http://dx.doi. org/10.1053/j.gastro.2006.03.008.
54. Chitkara DK, Rawat DJ, Talley NJ. The epidemiology of childhood recurrent abdominal pain in Western countries: a systematic review. Am J Gastroenterol 2005; 100:1868-75; PMID:16086724; http://dx.doi. org/10.1111/j.1572-0241.2005.41893.x.
55. Ringel Y, Drossman DA. Irritable Bowel Syndrome. In: MA RMaG, ed. Netter's textbook of Internal Medicine: Sauders elsevier, 2009:419-25.
56. Saito YA. The role of genetics in IBS. Gastroenterol Clin North Am 2011; 40:45-67; PMID:21333900; http://dx.doi.org/10.1016/j.gtc.2010.12.011.
57. Ringel Y, Carroll IM. Alterations in the intestinal microbiota and functional bowel symptoms. [vii.]. Gastrointest Endosc Clin N Am 2009; 19:141-50, vii; PMID:19232285; http://dx.doi.org/10.1016/j. giec.2008.12.004.
58. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil 2012; 24:521-30, e248; PMID:22339879; http://dx.doi.org/10.1111/j.1365-2982.2012.01891.x.
59. Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, Raza S, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 2011; 141:1782-91; PMID:21741921; http://dx.doi.org/10.1053/j. gastro.2011.06.072.
60. Rajilić-Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141:1792-801; PMID:21820992; http://dx.doi.org/10.1053/j.gastro. 2011.07.043.
61. Parkes GC, Rayment NB, Hudspith BN, Petrovska L, Lomer MC, Brostoff J, et al. Distinct microbial populations exist in the mucosa-associated microbiota of subgroups of irritable bowel syndrome. Neurogastroenterol Motil 2012; 24:31-9; PMID:22070725; http://dx.doi. org/10.1111/j.1365-2982.2011.01803.x.
62. Duboc H, Rainteau D, Rajca S, Humbert L, Farabos D, Maubert M, et al. Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil 2012; 24:513-20, e246-7; PMID:22356587; http://dx.doi.org/10.1111/j.1365-2982.2012.01893.x.
63. Krogius-Kurikka L, Lyra A, Malinen E, Aarnikunnas J, Tuimala J, Paulin L, et al. Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoeapredominant irritable bowel syndrome sufferers. BMC Gastroenterol 2009; 9:95; PMID:20015409; http://dx.doi.org/10.1186/1471-230X-9-95.
64. Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010; 59:325-32; PMID:19091823; http://dx.doi.org/10.1136/gut.2008.167270.
65. Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, et al. Prebiotic effects: metabolic and health benefits. Br J Nutr 2010; 104(Suppl 2):S1-63; PMID:20920376; http://dx.doi.org/10.1017/S0007114510003363.
66. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, et al.; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011; 364:22-32; PMID:21208106; http://dx.doi.org/10.1056/NEJMoa1004409.
67. Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol 2009; 104:1033-49, quiz 1050; PMID:19277023; http://dx.doi.org/10.1038/ajg.2009.25.
68. Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syndrome--focus on lactic acid bacteria. Aliment Pharmacol Ther 2012; 35:403-13; PMID:22225517; http://dx.doi.org/10.1111/j.1365-2036.2011.04965.x.
69. Hoveyda N, Heneghan C, Mahtani KR, Perera R, Roberts N, Glasziou P. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol 2009; 9:15; PMID:19220890; http://dx.doi.org/10.1186/1471-230X-9-15.
70. Ringel Y, Ringel-Kulka T. The rationale and clinical effectiveness of probiotics in irritable bowel syndrome. J Clin Gastroenterol 2011; 45(Suppl):S145-8; PMID:21992954; http://dx.doi.org/10.1097/MCG.0b013e31822d32d3.
71. Martínez C, Lobo B, Pigrau M, Ramos L, González-Castro AM, Alonso C, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2012; In press; PMID:22637702; http://dx.doi. org/10.1136/gutjnl-2012-302093.
72. Zeng J, Li YQ, Zuo XL, Zhen YB, Yang J, Liu CH. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2008; 28:994-1002; PMID:18671775; http://dx.doi.org/10.1111/j.1365-2036.2008.03818.x.
73. Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, et al. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol 2008; 295:G1025-34; PMID:18787064; http://dx.doi.org/10.1152/ajpgi.90227.2008.
74. Nissen L, Chingwaru W, Sgorbati B, Biavati B, Cencic A. Gut health promoting activity of new putative probiotic/protective Lactobacillus spp. strains: a functional study in the small intestinal cell model. Int J Food Microbiol 2009; 135:288-94; PMID:19775767; http://dx.doi.org/10.1016/j.ijfoodmicro.2009.08.027.
75. Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 2003; 52:988-97; PMID:12801956; http://dx.doi. org/10.1136/gut.52.7.988.
76. de Preter V, Vanhoutte T, Huys G, Swings J, Rutgeerts P, Verbeke K. Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment Pharmacol Ther 2008; 27:504-13; PMID:18081736; http://dx.doi. org/10.1111/j.1365-2036.2007.03588.x.
77. Lewis S, Burmeister S, Brazier J. Effect of the prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: a randomized, controlled study. Clin Gastroenterol Hepatol 2005; 3:442-8; PMID:15880313; http://dx.doi.org/10.1016/S1542-3565(04)00677-9.
78. Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O'neil DA, et al. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 2005; 54:242-9; PMID:15647189; http://dx.doi. org/10.1136/gut.2004.044834.
79. Casellas F, Borruel N, Torrejón A, Varela E, Antolin M, Guarner F, et al. Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 2007; 25:1061-7; PMID:17439507; http://dx.doi.org/10.1111/j.1365-2036.2007.03288.x.
80. Olesen M, Gudmand-Hoyer E. Efficacy, safety and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome. Am J Clin Nutr 2000; 72:1570-5; PMID:11101487.
81. Gibson PR, Shepherd SJ. Food choice as a key management strategy for functional gastrointestinal symptoms. Am J Gastroenterol 2012; 107:657-66, quiz 667; PMID:22488077; http://dx.doi.org/10.1038/ajg.2012.49.
82. Paineau D, Payen F, Panserieu S, Coulombier G, Sobaszek A, Lartigau I, et al. The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort of subjects with minor functional bowel disorders. Br J Nutr 2008; 99:311-8; PMID:17697398; http://dx.doi.org/10.1017/S000711450779894X.
83. Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2009; 29:508-18; PMID:19053980; http://dx.doi. org/10.1111/j.1365-2036.2008.03911.x.
84. Brownawell AM, Caers W, Gibson GR, Kendall CW, Lewis KD, Ringel Y, et al. Prebiotics and the health benefits of fiber: current regulatory status, future research and goals. J Nutr 2012; 142:962-74; PMID:22457389; http://dx.doi.org/10.3945/jn.112.158147.
85. Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 2012; 9:286-94; PMID:22392290; http://dx.doi. org/10.1038/nrgastro.2012.32.
86. Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 2010; 139:2102-12, e1; PMID:20600016; http://dx.doi. org/10.1053/j.gastro.2010.06.063.
87. Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 2011; 141:599-609, 609, e1-3; PMID:21683077; http://dx.doi.org/10.1053/j. gastro.2011.04.052.
88. Clarke G, O'Mahony SM, Hennessy AA, Ross P, Stanton C, Cryan JF, et al. Chain reactions: early-life stress alters the metabolic profile of plasma polyunsaturated fatty acids in adulthood. Behav Brain Res 2009; 205:319-21; PMID:19616034; http://dx.doi. org/10.1016/j.bbr.2009.07.008.
89. O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, et al. Early life stress alters behavior, immunity and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 2009; 65:263-7; PMID:18723164; http://dx.doi.org/10.1016/j.biopsych. 2008.06.026.