Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases

Current Opinion in Infectious Diseases

Volumn 22, Issue 3, 2009, Pages 292-301

  Packey, Christopher D ^a   Sartor, R Balfour ^a  

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

Author keywords

Bacteria; Commensals; Dysbiosis; IBD; Probiotics

Indexed keywords

ALPHA DEFENSIN; AMINOSALICYLIC ACID; BETA DEFENSIN; CARCINOEMBRYONIC ANTIGEN RELATED CELL ADHESION MOLECULE 6; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CLARITHROMYCIN; CYTOKINE; ETHAMBUTOL; FLAGELLIN; HY 7801; INTERFERON; ISPAGULA; OUTER MEMBRANE PROTEIN C; PREDNISOLONE; PROBIOTIC AGENT; RIFABUTIN; T CELL FACTOR PROTEIN; T CELL FACTOR PROTEIN 4; TRINITROBENZENESULFONIC ACID; UNCLASSIFIED DRUG; VSL3; WNT PROTEIN; X BOX BINDING PROTEIN 1;

BACTERIAL VIRULENCE; BACTERICIDAL ACTIVITY; BACTEROIDES FRAGILIS; BACTEROIDETES; BIFIDOBACTERIUM ANIMALIS; BIFIDOBACTERIUM BIFIDUM; BIFIDOBACTERIUM BREVE; BIFIDOBACTERIUM LONGUM; BIFIDOBACTERIUM LONGUM INFANTIS; BIODIVERSITY; CHRONIC GRANULOMATOUS DISEASE; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE; COLITIS; COMMENSAL; CROHN DISEASE; DNA POLYMORPHISM; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG TOLERABILITY; ENTERITIS; ENTEROBACTERIACEAE; ENTEROCOCCUS; ENTEROCOCCUS DURANS; ESCHERICHIA COLI; FAECALIBACTERIUM PRAUSNITZII; FIRMICUTES; FLUORESCENCE IN SITU HYBRIDIZATION; HELICOBACTER; HUMAN; ILEITIS; IMMUNE RESPONSE; IRRITABLE COLON; LACTOBACILLUS; LACTOBACILLUS ACIDOPHILUS; LACTOBACILLUS BULGARICUS; LACTOBACILLUS CASEI; LACTOBACILLUS DELBRUECKII; LACTOBACILLUS GASSERI; LACTOBACILLUS JOHNSONII; LACTOBACILLUS PLANTARUM; LACTOBACILLUS REUTERI; LACTOBACILLUS RHAMNOSUS; LACTOBACILLUS SUNTORYEUS; MICROFLORA; MOLECULAR BIOLOGY; MYCOBACTERIUM PARATUBERCULOSIS; NONHUMAN; OPPORTUNISTIC INFECTION; PANETH CELL; PATHOGENESIS; PATHOPHYSIOLOGY; POLYMERASE CHAIN REACTION; RECURRENT DISEASE; REVIEW; SIGNAL TRANSDUCTION; STREPTOCOCCUS THERMOPHILUS; ULCERATIVE COLITIS; BACTERIUM; GASTROINTESTINAL TRACT; GENETICS; IMMUNOLOGY; MICROBIOLOGY; MUCOSAL IMMUNITY; PATHOGENICITY;

BACTERIA; BIODIVERSITY; GASTROINTESTINAL TRACT; HUMANS; IMMUNITY, MUCOSAL; INFLAMMATORY BOWEL DISEASES; PROBIOTICS;

EID: 65549129496     PISSN: 09517375     EISSN: 14736527     Source Type: Journal    
DOI: 10.1097/QCO.0b013e32832a8a5d     Document Type: Review

References (82)

1. Kappelman M, Rifas-Shiman SL, Porter CQ, et al. Direct healthcare costs of Crohn's disease and ulcerative colitis in US children and adults. Gastroenterology 2008; 135:1907-1913. This study estimates the direct costs of Crohn's disease and ulcerative colitis in over 19 000 patients in the USA, describes the distribution of costs and identifies sociodemographic factors that influence these costs.
2. Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology 2008; 134:577-594. This comprehensive review outlines the roles of commensal bacterial species, host genetic polymorphisms and hyperactive immune responses in the pathogenesis of IBD.
3. Winslet MC, Allan A, Poxon V, et al. Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process. Gut 1994; 35:236-242.
4. Kang SS, Bloom SM, Norian LA, et al. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Medicine 2008; 5:e41.
5. Korzenik JR. Is Crohn's disease due to defective immunity? Gut 2007; 56: 2-5.
6. Wehkamp J, Salzman NH, Porter E, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 2005; 102:18129-18134.
7. Fellermann K, Stange DE, Schaeffeler E, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006; 79:439-448.
8. Wehkamp J, Wang G, Kubler I, et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol 2007; 179:3109-3118.
9. Kobayashi KS, Chamaillard M, Ogura Y, et al. NOD2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005; 307:731-734.
10. Cadwell K, Liu JY, Brown SL, et al. A key role for autophagy and the autophagy gene ATG16L1 in mouse and human intestinal Paneth cells. Nature 2008; 456:259-263. This study reports a novel link between autophagy, the biological function of Paneth cells and IBD.
11. -/- mice were generated, with evidence of ER stress, absent Paneth cells, and susceptibility to experimental colitis. The association between single nucleotide polymorphisms within the XBP1 gene region, endoplasmic reticulum stress and IBD in a German cohort of over 1000 patients with IBD and 1000 controls makes these findings more compelling.
12. Prescott NJ, Fisher SA, Franke A, et al. A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5. Gastroenterology 2007; 132:1665-1671. The T300A variant of ATG16L1 was genotyped in two cohorts in the UK totaling over 1200 Crohn's disease patients and 1200 controls, and was found to confer a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease.
13. Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007; 39:596-604. A strong and significantly replicated association was made between ileal Crohn's disease and a coding variant in ATG16L1 in this study, which included 988 patients with ileal Crohn's disease and over 1000 controls. ATG16L1 was also shown to be expressed in intestinal epithelial cell lines and involved in killing an intracellular pathogen.
14. Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008; 40:955-962. This study combined data from three previous studies on Crohn's disease, including 3230 cases and 4829 controls, and confirmed 11 previously reported loci while providing genome-wide significant evidence for 21 additional loci. This study is important because it provides the largest set of patients for Crohn's disease genome-wide association studies.
15. Sartor RB. Does Mycobacterium avium subspecies paratuberculosis cause Crohn's disease? Gut 2005; 54:896-898.
16. Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic char-acterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007; 104:13780-13785. This study reveals differences in microbiotas between patients with IBD and healthy controls, notably a depletion of members of the phyla Firmicutes and Bacteroidetes in IBD. F. prausnitzii is one of the bacterial species found to be depleted in the tissues of IBD patients.
17. Baumgart M, Dogan B, Rishniw M, et al. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME J 2007; 1:403-418. Invasive E. coli was linked to ileal Crohn's disease in this study, with enrichment of their sequences in inflamed ileal mucosa. The number of E. coli in situ correlated with the severity of ileal disease.
18. Scanu AM, Bull TJ, Cannas S, et al. Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease: common neural and immune pathogenicities. J Clin Microbiol 2007; 45:3883-3890.
19. Toracchio S, El-Zimaity HM, Urmacher C, et al. Mycobacterium avium subspecies paratuberculosis and Crohn's disease granulomas. Scand J Gastroenterol 2008; 43:1108-1111.
20. Singh AV, Singh SV, Makharia GK, et al. Presence and characterization of Mycobacterium avium subspecies paratuberculosis from clinical and suspected cases of Crohn's disease and in the healthy human population in India. Int J Infect Dis 2008; 12:190-197.
21. Bentley RW, Keenan JI, Gearry RB, et al. Incidence of Mycobacterium avium subspecies paratuberculosis in a population-based cohort of patients with Crohn's disease and control subjects. Am J Gastroenterol 2008; 103:1168-1172.
22. Juste RA, Elguezabal N, Garrido JM, et al. On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease. PLoS ONE 2008; 3:e2537.
23. Clancy R, Ren Z, Turton J, et al. Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion. Dig Liver Dis 2007; 39:445-451.
24. Ren Z, Turton J, Borody T, et al. Selective Th2 pattern of cytokine secretion in Mycobacterium avium subsp. paratuberculosis infected Crohn's disease. J Gastroenterol Hepatol 2008; 23:310-314.
25. Jeyanathan M, Boutros-Tadros O, Radhi J, et al. Visualization of Mycobacterium avium in Crohn's tissue by oil-immersion microscopy. Microbes Infect 2007; 9:1567-1573.
26. Bernstein CN, Wang MH, Sargent M, et al. Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in cases of inflammatory bowel disease. J Clin Microbiol 2007; 45:968-971. This study reports a lack of association between MAP serologies and NOD2 polymorphisms.
27. Abubakar I, Myhill DJ, Hart AR, et al. A case-control study of drinking water and dairy products in Crohn's Disease-further investigation of the possible role of Mycobacterium avium paratuberculosis. Am J Epidemiol 2007; 165:776-783. This epidemiological survey refuted any association between MAP and contamination of water sources in the UK. This is important because of the historical concern regarding potential transmission of MAP through water sources.
28. Selby W, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease. Gastroenterology 2007; 132:2313-2319. This large, placebo-controlled trial reported no sustained benefit of triple anti-mycobacterial therapy.
29. Singh UP, Singh S, Singh R, et al. Influence of Mycobacterium avium subsp. paratuberculosis on colitis development and specific immune responses during disease. Infect Immun 2007; (8):3722-3728.
30. Darfeuille-Michaud A, Boudeau J, Bulois P, et al. High prevalence of adherentinvasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 2004; 127:412-421.
31. Barnich N, Darfeuille-Michaud A. Adherent-invasive Escherichia coli and Crohn's disease. Curr Opin Gastroenterol 2007; 23:16-20.
32. Sasaki M, Sitaraman SV, Babbin BA, et al. Invasive Escherichia coli are a feature of Crohn's disease. Lab Invest 2007; 87:1042-1054. Invasive strains of E. coli were strongly associated with Crohn's disease by gentamicin protection assays and biochemical profiling.
33. Meconi S, Vercellone A, Levillain F, et al. Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro. Cell Microbiol 2007; 9:1252-1261. Prototypical AIEC LF82 selectively induced the aggregation of infected human macrophages to form granulomas.
34. Mow WS, Vasiliauskas EA, Lin YC, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gas-troenterology 2004; 126:414-424.
35. E pathway are involved in adhesion and invasion of the Crohn's disease-associated Escher-ichia coli strain LF82. Mol Microbiol 2007; 63:1684-1700. One of a series of important studies by Darfeuille-Michaud's group investigating the pathways utilized by the prototype AIEC strain to adhere to and invade epithelial cells.
36. Carvalho FA, Barnich N, Sauvanet P, et al. Crohn's disease-associated Escherichia coli LF82 aggravates colitis in injured mouse colon via signaling by flagellin. Inflamm Bowel Dis 2008; 14:1051-1060. Mechanisms by which nonpathogenic E. coli strains acquire virulence are elucidated in this animal model.
37. Bringer MA, Rolhion N, Glasser AL, Darfeuille-Michaud A. The oxidoreductase DsbA plays a key role in the ability of the Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 to resist macrophage killing. J Bacteriol 2007; 189:4860-4871. Molecular mechanisms by which LF82 resist macrophage killing is elucidated. AIEC can replicate intracellularly within macrophages.
38. Eaves-Pyles T, Allen CA, Taormina J, et al. Escherichia coli isolated from a Crohn's disease patient adhere, invade, and induce inflammatory responses in polarized intestinal epithelial cells. Int J Med Microbiol 2008; 298:397-409. In this study, AIEC strains isolated from patients with Crohn's disease demonstrated the ability to induce inflammatory responses in Caco-2BBe and T-84 intestinal epithelial cells in in-vitro experiments.
39. Barnich N, Carvalho FA, Glasser AL, et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn's disease. J Clin Invest 2007; 117:1566-1574. The adhesion characteristics of AIEC that are implicated in the pathogenesis of IBD are investigated in this study by Darfeuille-Michaud's group. Ileal epithelial cells of patients with Crohn's disease express higher levels of CEACAM 6, which is further up-regulated by AIEC exposure.
40. Peeters H, Bogaert S, Laukens D, et al. CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease. Int J Immunogenet 2007; 34:181-191. This is one of the first, important attempts to investigate associations between polymorphisms linked to Crohn's disease and the adhesion and invasion characteristics of AIEC.
41. Liu B, Schmitz JM, Holt LC, et al. Increased intracellular survival of E. coli NC101 within macrophages may contribute to its ability to induce colitis [abstract]. Gastroenterology (in press).
42. Porter CK, Tribble DR, Aliaga PA, et al. Infectious gastroenteritis and risk of developing inflammatory bowel disease. Gastroenterology 2008; 135:781-786.
43. Issa M, Vijayapal A, Graham MB, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007; 5:345-351. The role of a traditional triggering pathogen in the pathogenesis of IBD is explored.
44. Kim H, Rhee SH, Pothoulakis C, et al. Inflammation and apoptosis in Clostridium difficile enteritis is mediated by PGE(2) up-regulation of Fas ligand. Gastroenterology 2007; 133:875-886.
45. Rabizadeh S, Rhee KJ, Wu S, et al. Enterotoxigenic Bacteroides fragilis: a potential instigator of colitis. Inflamm Bowel Dis 2007; 13:1475-1483.
46. Veijola L, Nilsson I, Halme L, et al. Detection of Helicobacter species in chronic liver disease and chronic inflammatory bowel disease. Ann Med 2007; 39:554-560.
47. Lupp C, Robertson ML, Wickham ME, et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2007; 2:119-129.
48. Kotlowski R, Bernstein CN, Sepehri S, Krause DO. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut 2007; 56:669-675. This study corroborates findings from previous studies that E. coli are increased in tissues of patients with IBD. A novel finding of this study is the higher prevalence of E. coli from the B2 + D phylogenetic group in these tissues. In addition, serine protease autotransporters were also found to be more prevalent in isolates from patients with IBD.
49. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 2008; 105:16731-16736. F. prausnitzii decreased IL-12 and IFN-γ production in stimulated peripheral blood mononuclear cells, and reduced the severity of TNBS colitis after being fed to mice. These results suggest that counterbalancing dysbiosis using F. prausnitzii could be a means of reducing inflammation in IBD patients.
50. Swidsinski A, Loening-Baucke V, Vaneechoutte M, Doerffel Y. Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis 2008; 14:147-161. In this study, FISH was used to compare the mucosa-associated microbiota (MAM) of patients with IBD and healthy controls. F. prausnitzii were found to be depleted in the tissues of patients with Crohn's disease and increased in the tissues of patients with ulcerative colitis.
51. Andoh A, Sakata S, Koizumi Y, et al. Terminal restriction fragment length polymorphism analysis of the diversity of fecal microbiota in patients with ulcerative colitis. Inflamm Bowel Dis 2007; 13:955-962. Dysbiosis was seen in the feces of patients with ulcerative colitis using terminal restriction fragment length polymorphism (T-RFLP).
52. Takaishi H, Matsuki T, Nakazawa A, et al. Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int J Med Microbiol 2008; 298:463-472.
53. Dicksved J, Halfvarson J, Rosenquist M, et al. Molecular analysis of the gut microbiota of identical twins with Crohn's disease. ISME J 2008; 2: 716-727. This study is novel in that it analyzes the microbiotas of monozygotic twin pairs with and without Crohn's disease.
54. Nishikawa J, Kudo T, Sakata S, et al. Diversity of mucosa-associated microbiota in active and inactive ulcerative colitis. Scand J Gastroenterol 2008; 30:1-7. Using T-RFLP, this study demonstrated in a small cohort that the MAM of patients with active ulcerative colitis differs from that of patients with inactive disease. Microbial compositions were more diverse in patients with inactive ulcerative colitis when compared to patients with active disease.
55. Ott SJ, Plamondon S, Hart A, et al. Dynamics of the mucosa-associated flora in ulcerative colitis patients during remission and clinical relapse. J Clin Microbiol 2008; 46:3510-3513. Patients with ulcerative colitis were found to have less biodiversity in their MAM than healthy controls.
56. Martinez C, Antolin M, Santos J, et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 2008; 103:643-648. PCR and denaturing gradient gel electrophoresis (DGGE) revealed that patients with ulcerative colitis who do not have active disease demonstrate low biodiversity and temporal instability in their fecal microbiota.
57. Zhang M, Liu B, Zhang Y, et al. Structural shifts of mucosa-associated Lactobacilli and Clostridium leptum subgroup in patients with ulcerative colitis. J Clin Microbiol 2007; 45:496-500.
58. Vasquez N, Mangin I, Lepage P, et al. Patchy distribution of mucosal lesions in ileal Crohn's disease is not linked to differences in the dominant mucosa-associated bacteria: a study using fluorescence in situ hybridization and temporal temperature gradient gel electrophoresis. Inflamm Bowel Dis 2007; 13:684-692.
59. Bäckhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism in the human intestine. Science 2005; 307:1915-1920.
60. Kim SC, Tonkonogy SL, Karrasch T, et al. Dual-association of gnotobiotic IL-10-/-mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis. Inflamm Bowel Dis 2007; 13:1457-1466. Demonstration that in the setting of immunoregulatory defects, nonpathogenic bacteria have additive effects in causing immune-mediated colitis.
61. Keita AV, Salim SY, Jiang T, et al. Increased uptake of nonpathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease. J Pathol 2008; 215:135-144. This is an important study because it demonstrates that in IBD, typically nonpathogenic bacteria such as E. coli strains K-12 and HB101 can cause inflammation through increased intercellular and transcellular uptake. This was demonstrated by E. coli strains isolated from the tissue of patients with Crohn's disease, but not in strains isolated from ulcerative colitis patient specimens.
62. Roediger WE. Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis. Aliment Pharmacol Ther 2008; 27:531-541. This review summarizes novel studies investigating metabolic properties of bacteria that may play key roles in the pathogenesis of ulcerative colitis, which should stimulate further investigations.
63. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology 2004; 126:1620-1633.
64. Boirivant M, Strober W. The mechanism of action of probiotics. Curr Opin Gastroenterol 2007; 23:679-692. This review offers background on the use of probiotics, the mechanisms of action of probiotics and the effects of probiotics on epithelial barrier function, lymphoid cells, development of regulatory cells, inflammatory responses and IBD.
65. Sheil B, Shanahan F, O'Mahony L. Probiotic effects on inflammatory bowel disease. J Nutr 2007; 137:S819-S824.
66. Hedin C, Whelan K, Lindsay JO. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proc Nutr Soc 2007; 66:307-315.
67. Isaacs K, Herfarth H. Role of probiotic therapy in IBD. Inflamm Bowel Dis 2008; 14:1597-1605. This is an excellent, comprehensive review of past clinical trials investigating the use of probiotics to treat Crohn's disease, ulcerative colitis and pouchitis.
68. Peran L, Camuesco D, Comalada M, et al. A comparative study of the preventive effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis. J Appl Microbiol 2007; 103:836-844.
69. Llopis M, Antolin M, Carol M, et al. Lactobacillus casei downregulates commensals' inflammatory signals in Crohn's disease mucosa. Inflamm Bowel Dis 2009; 15:275-283.
70. Kim N, Kunisawa J, Kweon MN, et al. Oral feeding of Bifidobacterium bifidum (BGN4) prevents CD4(+) CD45RB(high) T cell-mediated inflammatory bowel disease by inhibition of disordered T cell activation. Clin Immunol 2007; 123:30-39. This study identifies a probiotic that can inhibit disordered T cell activation in mice. In humans, dysregulation of T cell activation is an important component of IBD.
71. Carroll IM, Andrus JM, Bruno-Barcena JM, et al. Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 2007; 293:G729-G738. This study demonstrates the intricate connection between regulation of the immune system and metabolic properties of commensal bacteria.
72. Lee JH, Lee B, Lee HS, et al. Lactobacillus suntoryeus inhibits proinflammatory cytokine expression and TLR-4-linked NF-kappaB activation in experimental colitis. Int J Colorectal Dis 2009; 24:231-237. This study investigates the effects of probiotics on the NF-κB (an important transcription regulator) pathway, which is intimately linked to inflammation.
73. Imaoka A, Shima T, Kato K, et al. Anti-inflammatory activity of probiotic Bifidobacterium: enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells. World J Gastroenterol 2008; 14:2511-2516.
74. Lin YP, Thibodeaux CH, Peña JA, et al. Probiotic Lactobacillus reuteri suppresses proinflammatory cytokines via c-Jun. Inflamm Bowel Dis 2008; 14:1068-1083. This study demonstrates that secreted factors of probiotics can possess immunoregulatory capabilities.
75. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305-309.
76. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124:1202-1209.
77. Fitzpatrick LR, Hertzog KL, Quatse AL, et al. Effects of the probiotic formulation VSL#3 on colitis in weanling rats. J Pediatr Gastroenterol Nutr 2007; 44:561-570.
78. Huynh HQ, Debruyn J, Guan L, et al. Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: a pilot study. Inflamm Bowel Dis 2009 [Epub ahead of print]. The probiotic preparation VSL#3 induced remission in children with ulcerative colitis in a small clinical trial.
79. Pronio A, Montesani C, Butteroni C, et al. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis 2008; 14:662-668. VSL#3 was found to treat pouchitis in this open-label clinical trial involving 31 patients.
80. Fujimori S, Tatsuguchi A, Gudis K, et al. High dose antibiotic and prebiotic cotherapy for remission induction of active Crohn's disease. J Gastroenterol Hepatol 2007; 22:1199-1204. In a small cohort, this study showed that high-dose probiotics are well tolerated by human patients, and that two components of the much-studied probiotic preparation VSL#3 may hold promise for inducing remission in ulcerative colitis patients, even in a subset that has failed other treatments.
81. Raz I, Gollop N, Polak-Charcon S, Schwartz B. Isolation and characterization of new putative probiotic bacteria from human colonic flora. Br J Nutr 2007; 97:725-734. Enterococcus durans was found to reduce inflammation in Balb/c mice in the DSS model of colitis. More importantly, this study emphasizes the importance of characterizing various commensal bacteria in the hope of discovering a novel probiotic species to treat ulcerative colitis or Crohn's disease.
82. Van Gossum A, Dewit O, Louis E, et al. Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after ileo-caecal resection. Inflamm Bowel Dis 2007; 13:135-142.