Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases

Probiotics and synbiotics are used to treat chronic diseases, principally due to their role in immune system modulation and the anti-inflammatory response. The present study reviewed the effects of probiotics and synbiotics on intestinal chronic diseases in in vitro, animal, and human studies, particularly in randomized clinical trials. The selected probiotics exhibit in vitro anti-inflammatory properties. Probiotic strains and cell-free supernatants reduced the expression of pro-inflammatory cytokines via action that is principally mediated by toll-like receptors. Probiotic administration improved the clinical symptoms, histological alterations, and mucus production in most of the evaluated animal studies, but some results suggest that caution should be taken when administering these agents in the relapse stages of IBD. In addition, no effects on chronic enteropathies were reported. Probiotic supplementation appears to be potentially well tolerated, effective, and safe in patients with IBD, in both CD and UC. Indeed, probiotics such as Bifidobacterium longum 536 improved the clinical symptoms in patients with mild to moderate active UC. Although it has been proposed that probiotics can provide benefits in certain conditions, the risks and benefits should be carefully assessed before initiating any therapy in patients with IBD. For this reason, further studies are required to understand the precise mechanism by which probiotics and synbiotics affect these diseases.

[1]  D. Aust,et al.  Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group. , 2012, Journal of Crohn's & colitis.

[2]  R. Dorfman,et al.  Mucosa-reparing and microbiota-balancing therapeutic effect of Bacillus subtilis alleviates dextrate sulfate sodium-induced ulcerative colitis in mice , 2016, Experimental and therapeutic medicine.

[3]  Zhongjian Chen,et al.  Protective effects of Lactobacillus plantarum on epithelial barrier disruption caused by enterotoxigenic Escherichia coli in intestinal porcine epithelial cells. , 2016, Veterinary immunology and immunopathology.

[4]  Á. Gil,et al.  Lactobacillus rhamnosus and its cell-free culture supernatant differentially modulate inflammatory biomarkers in Escherichia coli-challenged human dendritic cells. , 2014, The British journal of nutrition.

[5]  C. Langner,et al.  Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. , 2017, Journal of Crohn's & colitis.

[6]  L. Morelli,et al.  FAO Technical meeting on prebiotics. , 2008, Journal of clinical gastroenterology.

[7]  F. Romero,et al.  Cell-Free Culture Supernatant of Bifidobacterium breve CNCM I-4035 Decreases Pro-Inflammatory Cytokines in Human Dendritic Cells Challenged with Salmonella typhi through TLR Activation , 2013, PloS one.

[8]  Y. Ringel,et al.  Alterations in the intestinal microbiota and functional bowel symptoms. , 2009, Gastrointestinal endoscopy clinics of North America.

[9]  Subrata Ghosh,et al.  Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. , 2012, Gastroenterology.

[10]  Adolfo Suárez,et al.  Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. , 2014, World journal of gastroenterology.

[11]  J. Macfie,et al.  Impact of probiotics on colonic microflora in patients with colitis: a prospective double blind randomised crossover study. , 2013, International journal of surgery.

[12]  J. Leblanc,et al.  Effect of probiotic administration on the intestinal microbiota, current knowledge and potential applications. , 2014, World journal of gastroenterology.

[13]  P. O’Toole,et al.  Probiotic Bacteria Influence the Composition and Function of the Intestinal Microbiota , 2008, Interdisciplinary perspectives on infectious diseases.

[14]  Yue-jiao Shi,et al.  Study on the effects of microencapsulated Lactobacillus delbrueckii on the mouse intestinal flora , 2015, Journal of microencapsulation.

[15]  Xia Yang 杨 霞,et al.  Impact of probiotics on toll-like receptor 4 expression in an experimental model of ulcerative colitis , 2013, Journal of Huazhong University of Science and Technology [Medical Sciences].

[16]  A. Kraneveld,et al.  Specific probiotic dietary supplementation leads to different effects during remission and relapse in murine chronic colitis. , 2016, Beneficial microbes.

[17]  G R Gibson,et al.  Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. , 1995, The Journal of nutrition.

[18]  A. Hart,et al.  Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota , 2013, Mediators of inflammation.

[19]  F. Abadía-Molina,et al.  Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains , 2017, Scientific Reports.

[20]  D. Werling,et al.  Effects of Ex-Vivo and In-Vivo Treatment with Probiotics on the Inflammasome in Dogs with Chronic Enteropathy , 2015, PloS one.

[21]  D. Raoult,et al.  Lactobacillus rhamnosus bacteremia: an emerging clinical entity , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[22]  A. Margolles,et al.  Association of Levels of Antibodies from Patients with Inflammatory Bowel Disease with Extracellular Proteins of Food and Probiotic Bacteria , 2014, BioMed research international.

[23]  M. Geier,et al.  Effects of a Lactobacillus reuteri BR11 Mutant Deficient in the Cystine-Transport System in a Rat Model of Inflammatory Bowel Disease , 2012, Digestive Diseases and Sciences.

[24]  H. Rafa,et al.  Beneficial role of the probiotic mixture Ultrabiotique on maintaining the integrity of intestinal mucosal barrier in DSS-induced experimental colitis , 2013, Immunopharmacology and immunotoxicology.

[25]  M. Roberfroid Prebiotics and probiotics: are they functional foods? , 2000, The American journal of clinical nutrition.

[26]  G. Rossolini,et al.  Breakthrough Lactobacillus rhamnosus GG bacteremia associated with probiotic use in an adult patient with severe active ulcerative colitis: case report and review of the literature , 2015, Infection.

[27]  J M T Hamilton-Miller,et al.  Some insights into the derivation and early uses of the word ‘probiotic’ , 2003, British Journal of Nutrition.

[28]  H. Nakase,et al.  Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double‐blinded, placebo‐controlled multicenter trial , 2016, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society.

[29]  M. Roberfroid Prebiotics and probiotics: are they functional foods? , 2000, The American journal of clinical nutrition.

[30]  M. Geier,et al.  Probiotic factors partially prevent changes to caspases 3 and 7 activation and transepithelial electrical resistance in a model of 5-fluorouracil-induced epithelial cell damage , 2012, Supportive Care in Cancer.

[31]  T. Churchill,et al.  VSL#3 probiotics provide protection against acute intestinal ischaemia/reperfusion injury. , 2013, Beneficial microbes.

[32]  Tadao Saito,et al.  Lactobacillus delbrueckii TUA4408L and its extracellular polysaccharides attenuate enterotoxigenic Escherichia coli-induced inflammatory response in porcine intestinal epitheliocytes via Toll-like receptor-2 and 4. , 2014, Molecular nutrition & food research.

[33]  S. Salminen,et al.  Probiotics: an overview of beneficial effects , 2002, Antonie van Leeuwenhoek.

[34]  A. Bitton,et al.  The probiotic VSL#3 has anti-inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn's disease. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[35]  C. Dai,et al.  VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis , 2012, Molecular and Cellular Biochemistry.

[36]  K. Whelan,et al.  Fiber in the Treatment and Maintenance of Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials , 2014, Inflammatory bowel diseases.

[37]  Á. Gil,et al.  Pyrosequencing Analysis Reveals Changes in Intestinal Microbiota of Healthy Adults Who Received a Daily Dose of Immunomodulatory Probiotic Strains , 2015, Nutrients.

[38]  S. Vermeire,et al.  Butyricicoccus pullicaecorum in inflammatory bowel disease , 2012, Gut.

[39]  I. Elmadfa,et al.  Regulation of TLR4, p38 MAPkinase, IκB and miRNAs by inactivated strains of lactobacilli in human dendritic cells. , 2012, Beneficial microbes.

[40]  Á. Gil,et al.  Probiotic Mechanisms of Action , 2012, Annals of Nutrition and Metabolism.

[41]  C. Gómez-Llorente,et al.  International Immunonutrition Workshop Session 5 : Early programming of the immune system and the role of nutrition Role of Toll-like receptors in the development of immunotolerance mediated by probiotics , 2010 .

[42]  J. Galmiche,et al.  Saccharomyces boulardii does not prevent relapse of Crohn's disease. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[43]  C. S. Satish Kumar,et al.  Protective effect of Lactobacillus plantarum 21, a probiotic on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. , 2015, International immunopharmacology.

[44]  Elaheh Vahabnezhad,et al.  Lactobacillus bacteremia associated with probiotic use in a pediatric patient with ulcerative colitis. , 2013, Journal of clinical gastroenterology.

[45]  Elie. Metchnikoff The Prolongation of Life: Optimistic Studies , 2003 .

[46]  R. Lechler,et al.  Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epithelium , 2006, European journal of immunology.

[47]  T. R. Desai,et al.  Probiotics: A Review , 2012 .

[48]  S. Ng,et al.  Human Gut Dendritic Cells Drive Aberrant Gut-specific T-cell Responses in Ulcerative Colitis, Characterized by Increased IL-4 Production and Loss of IL-22 and IFN&ggr; , 2014, Inflammatory bowel diseases.

[49]  M. Comalada,et al.  The association of minocycline and the probiotic Escherichia coli Nissle 1917 results in an additive beneficial effect in a DSS model of reactivated colitis in mice. , 2011, Biochemical pharmacology.

[50]  Takuya Suzuki,et al.  Modulatory activity of Lactobacillus rhamnosus OLL2838 in a mouse model of intestinal immunopathology. , 2015, Immunobiology.

[51]  F. Romero,et al.  Human Intestinal Dendritic Cells Decrease Cytokine Release against Salmonella Infection in the Presence of Lactobacillus paracasei upon TLR Activation , 2012, PloS one.

[52]  S. Fiorucci,et al.  Inhibition of Chronic Ulcerative Colitis-associated Adenocarcinoma Development in Mice by VSL#3 , 2015, Inflammatory bowel diseases.

[53]  Á. Gil,et al.  Sources, isolation, characterisation and evaluation of probiotics , 2013, British Journal of Nutrition.

[54]  D. Werling,et al.  A Prospective, Randomized, Blinded, Placebo‐Controlled Pilot Study on the Effect of Enterococcus faecium on Clinical Activity and Intestinal Gene Expression in Canine Food‐Responsive Chronic Enteropathy , 2015, Journal of veterinary internal medicine.

[55]  Namita Singh,et al.  Fecal Microbial Transplant Via Nasogastric Tube for Active Pediatric Ulcerative Colitis , 2015, Journal of pediatric gastroenterology and nutrition.

[56]  J. Söderholm,et al.  The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis , 2013, Alimentary pharmacology & therapeutics.

[57]  F. Abadía-Molina,et al.  Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on Hepatic Steatosis in Zucker Rats , 2014, PloS one.

[58]  A. Krag,et al.  Profermin is Efficacious in Patients with Active Ulcerative Colitis—A Randomized Controlled Trial , 2013, Inflammatory bowel diseases.

[59]  H. Rafa,et al.  Mucosal intestinal alteration in experimental colitis correlates with nitric oxide production by peritoneal macrophages: Effect of probiotics and prebiotics , 2012, Immunopharmacology and immunotoxicology.

[60]  M. Kamm,et al.  Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial , 2017, The Lancet.

[61]  G. Gloor,et al.  Microbial composition analysis of Clostridium difficile infections in an ulcerative colitis patient treated with multiple fecal microbiota transplantations. , 2014, Journal of Crohn's & colitis.

[62]  D. Corella,et al.  Safety and Immunomodulatory Effects of Three Probiotic Strains Isolated from the Feces of Breast-Fed Infants in Healthy Adults: SETOPROB Study , 2013, PloS one.

[63]  Yasuo Suzuki,et al.  Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis. , 2015, World journal of gastroenterology.

[64]  A. Petersen,et al.  Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis: a double-blind randomized placebo controlled clinical trial. , 2014, Journal of Crohn's & colitis.

[65]  A. Bomba,et al.  Co-administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 with prebiotic inulin alleviates the intestinal inflammation in rats exposed to N,N-dimethylhydrazine. , 2015, International immunopharmacology.

[66]  G. Hwang,et al.  1H NMR-based metabonomic assessment of probiotic effects in a colitis mouse model , 2010, Archives of pharmacal research.

[67]  E. Szigethy,et al.  Inflammatory bowel disease. , 2011, Pediatric clinics of North America.

[68]  F. Hoentjen,et al.  Probiotics and prebiotics in ulcerative colitis. , 2016, Best practice & research. Clinical gastroenterology.

[69]  J. Plaza-Díaz,et al.  Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials , 2016, International journal of molecular sciences.

[70]  S. Salminen,et al.  The impact of probiotic on gut health. , 2009, Current drug metabolism.

[71]  Yinglin Xia,et al.  Vitamin D receptor pathway is required for probiotic protection in colitis. , 2015, American journal of physiology. Gastrointestinal and liver physiology.

[72]  C. Cho,et al.  Protective effects of cathelicidin‐encoding Lactococcus lactis in murine ulcerative colitis , 2012, Journal of gastroenterology and hepatology.

[73]  Glenn R. Gibson,et al.  The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic , 2014 .

[74]  T. Dinan,et al.  Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut , 2013, Gut microbes.

[75]  Xiaowei Liu,et al.  Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice , 2016, PloS one.