Synbiotics in Inflammatory Bowel Diseases: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Immunology | Nutrition & Dietetics | Gastroenterology & Hepatology
Contributor:
Tanvi Shinde
,
Kent Taylor

Inflammatory bowel disease (IBD) is a group of chronic relapsing gastrointestinal disorders that are characterized by inflammation of the gastrointestinal tract. The involvement of three distinct recurrent inflammatory features that sustains the chronic inflammation in IBD have been clearly identified that includes, disturbances in the gut microbiota, dysregulated immune response and altered colonic epithelial integrity. Dietary components such as prebiotic dietary fibres (DF) and probiotics due to their potential in modulating immune functions and influencing microbiota are promising strategies in the context of IBD. In this entry, we review the recent evidence from in-vivo studies to support the application of synergistic synbiotic carrying whole-plant complex prebiotic fibre and probiotic in resolving in the inflammatory cycle in IBD.

  • Probiotic
  • Prebiotic
  • Inflammation
  • Gut Health
  • Synbiotic
  • Microbiome
  • Sugarcane Dietary Fibre
  • IBD
  • Short Chain Fatty Acid
  • Gut Barrier

1. Introduction

Inflammatory bowel disease (IBD) is a group of chronic relapsing gastrointestinal tract (GIT) disorders including ulcerative colitis (UC) and Crohn’s disease (CD) that are characterized by inflammation of the gastrointestinal tract and dysbiosis of the gut microbiota[1]. The incidence of CD and UC is rising globally[2]. The adoption of “Westernised” diet low in fruits and vegetables has been blamed as a potential factor for the recent rise in IBD incidence[3][4]. Despite current medical treatments that focus primarily on immunosuppression[5], overall 20% of patients with CD still require surgery and over 10% of UC patients still require colectomy[6]. This highlights the urgent need for research into prevention and management of these complex pathologies to avoid debilitating complications and the need for substantial medical interventions.

2. Three-part inflammatory cycle in IBD

Although, the etiopathology of IBD remains largely unknown, emerging evidence supports the interrelated roles of genetic, environmental, microbial and immunological factors[7][8]. IBD is thought to result from an aberrant and continuing inflammatory response to commensal microbes in a genetically susceptible host[7]. Alterations in the intestinal epithelial and mucosal barrier are known to support bacterial translocation resulting in dysfunctional intestinal inflammatory cascade[9][10][11], leading to pathologic proliferation of inflammatory mediators. There is an increasing level of evidence highlighting the key role of intestinal microbiota in driving inflammatory response during disease development and progression[12][13][14]. The microbial imbalance in the colon, also known as gut dysbiosis, is associated with dysregulated immune responses that further disturbs the colonic health. Thus, IBD encompasses a distinct tripartite pathophysiological circuit involving altered colonic mucosal barrier, dysregulated immune response and gut microbial dysbiosis as hallmarks of this complex pathology[1]. 

3. Combining prebiotic and probiotic functionalities to break the inflammatory cycle in IBD

Given the complexity of the involvement of multiple factors in the onset, progression, and pathogenesis of IBD, preventive and therapeutic approaches that hinder or break the inflammatory circuit by resolving one or more of the pathophysiological inflammatory components are needed. In this view, probiotic and prebiotic dietary fibres (DF) that regulate immune parameters by influencing gut microbiota and colonic barrier functions are important in the context of IBD[15].  The use of synbiotic formulations that capture the synergy of probiotic and prebiotic functioning is considered a pragmatic approach to resolving the gut inflammatory cycle[15][16][17][18].

Mechanistic research evidence indicates augmented efficacy of synergistic synbiotic combinations in modulating gut inflammation. An in-vivo study utilising a synbiotic combination of whole-plant dietary fibre and spore probiotic have been confirmed to protect mice against chemically induced IBD, with synergistic effect being more profound than that observed for either probiotic or prebiotic alone[19].  Preconditioning of mice with synbiotic (sugarcane-derived complex whole-plant prebiotic DF and probiotic Bacillus coagulans spores) – supplemented diet proved significantly effective in repressing the onset and severity of Dextran-Sulfate-Sodium (DSS)-induced colitis in mice model of IBD. The synbiotic pre-supplementation resulted in a substantial prophylactic and anti-inflammatory effect, reducing disease severity, colonic damage, and inflammatory mediators while modulating the metabolite and short-chain fatty acids (SCFA) profiles of DSS-induced gut damage.

The synergistic synbiotic combination of whole-plant prebiotic sugarcane fibre and B. coagulans spores was also demonstrated to impart therapeutic effect by reducing established gut inflammation in a genetically mutant mice model of IBD[20]. While prebiotic and probiotic supplemented diet were effective in alleviating some inflammatory parameters, synergistic synbiotic was most efficacious in modulating local and systemic cytokine profiles, reduce colonic epithelial damage and ameliorating severity of diseases symptoms. Furthermore, synbiotic combination was confirmed to confer site-specific modulations in gut microbiota diversity and boosted SCFA levels along the entire colon length. This study also highlights the importance of fermentation of prebiotic fibre and concomitant production of SCFAs at uniform rate to nourish the whole colon (proximal and distal)[20][21][22].

The benefits from prebiotic dietary fibre are largely dependent on the presence and/or abundance of fibre-digesting gut bacteria to produce anti-inflammatory SCFAs with immune regulating properties[23][24]. However, dysbiosis in IBD with characteristic depletion of fibre-degrading-SCFA-producing bacterial members and concurrent reduced levels of SCFAs is commonly reported. Thus, lack of fibre-digesting gut members in IBD limits the health outcomes through consumption of fibre-rich diet during inflammatory dysbiotic state. Similarly, probiotic administration alone without a fibre substrate would also be unreliable to affect health outcomes.

Thus, co-administration of probiotic bacteria that can synergistically metabolise the administered prebiotic DF as synbiotic and consequently improve the probiotic activity to produce beneficial metabolites and influence the microbiota is imperative in positively modulating the microbial environment to induce immune homeostasis.

References

  1. Stephen M. Vindigni; Timothy L. Zisman; David L. Suskind; Christopher J. Damman; The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therapeutic Advances in Gastroenterology 2016, 9, 606-625, 10.1177/1756283x16644242.
  2. Gilaad G. Kaplan; The global burden of IBD: from 2015 to 2025. Nature Reviews Gastroenterology & Hepatology 2015, 12, 720-727, 10.1038/nrgastro.2015.150.
  3. Jason K Hou; Bincy Abraham; Hashem El-Serag; Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature. American Journal of Gastroenterology 2011, 106, 563-573, 10.1038/ajg.2011.44.
  4. Devendra K Amre; Savio D'souza; Kenneth Morgan; Gillian Seidman; Philippe Lambrette; Guy Grimard; David Israel; David Mack; Parviz Ghadirian; Colette Deslandres; et al. Imbalances in Dietary Consumption of Fatty Acids, Vegetables, and Fruits Are Associated With Risk for Crohn's Disease in Children. American Journal of Gastroenterology 2007, 102, 2016-2025, 10.1111/j.1572-0241.2007.01411.x.
  5. Nicholas J Talley; Maria T Abreu; Jean-Paul Achkar; Charles N Bernstein; Marla C Dubinsky; Stephen B Hanauer; Sunanda V Kane; William J Sandborn; Thomas A Ullman; Paul Moayyedi; et al. An Evidence-Based Systematic Review on Medical Therapies for Inflammatory Bowel Disease. American Journal of Gastroenterology 2011, 106, S2-S25, 10.1038/ajg.2011.58.
  6. Christine Rungoe; Ebbe Langholz; Mikael Andersson; Saima Basit; Nete M Nielsen; Jan Wohlfahrt; Tine Jess; Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979–2011. Gut 2014, 63, 1607-1616, 10.1136/gutjnl-2013-305607.
  7. Bernard Khor; Agnès Gardet; Ramnik J. Xavier; Genetics and pathogenesis of inflammatory bowel disease. Nature 2011, 474, 307-317, 10.1038/nature10209.
  8. R. J. Xavier; D. K. Podolsky; Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007, 448, 427-434, 10.1038/nature06005.
  9. Michelle L. Hermiston; Jeffrey I. Gordon; Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin. Science 1995, 270, 1203-1207, 10.1126/science.270.5239.1203.
  10. Gerd Bouma; Warren Strober; The immunological and genetic basis of inflammatory bowel disease. Nature Reviews Immunology 2003, 3, 521-533, 10.1038/nri1132.
  11. Gerd Bouma; Anjali Kaushiva; Warren Strober; Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology 2002, 123, 554-565, 10.1053/gast.2002.34752.
  12. Guillaume Pineton De Chambrun; Jean-Frédéric Colombel; Daniel Poulain; Arlette Darfeuille-Michaud; Pathogenic agents in inflammatory bowel diseases. Current Opinion in Gastroenterology 2008, 24, 440-447, 10.1097/mog.0b013e3283023be5.
  13. Dirk Gevers; Subra Kugathasan; Lee A. Denson; Yoshiki Vázquez-Baeza; Will Van Treuren; Boyu Ren; Emma Schwager; Dan Knights; Se Jin Song; Moran Yassour; et al. The Treatment-Naive Microbiome in New-Onset Crohn’s Disease. Cell Host & Microbe 2014, 15, 382-392, 10.1016/j.chom.2014.02.005.
  14. Dan Knights; Kara G. Lassen; Ramnik J. Xavier; Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut 2013, 62, 1505-1510, 10.1136/gutjnl-2012-303954.
  15. Andrzej Wasilewski; Marta Zielińska; Martin Storr; Jakub Fichna; Beneficial Effects of Probiotics, Prebiotics, Synbiotics, and Psychobiotics in Inflammatory Bowel Disease. Inflammatory Bowel Diseases 2015, 21, 1674-1682, 10.1097/mib.0000000000000364.
  16. H. Steed; G. T. Macfarlane; K. L. Blackett; B. Bahrami; N. Reynolds; S. V. Walsh; J. H. Cummings; S. Macfarlane; Clinical trial: the microbiological and immunological effects of synbiotic consumption - a randomized double-blind placebo-controlled study in active Crohn’s disease. Alimentary Pharmacology & Therapeutics 2010, 32, 872-883, 10.1111/j.1365-2036.2010.04417.x.
  17. Shunji Fujimori; Katya Gudis; Keigo Mitsui; Tsuguhiko Seo; Masaoki Yonezawa; Shu Tanaka; Atsushi Tatsuguchi; Choitsu Sakamoto; A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition 2009, 25, 520-525, 10.1016/j.nut.2008.11.017.
  18. Tanvi Shinde; Agampodi Promoda Perera; Ravichandra Vemuri; Shakuntla V. Gondalia; David J. Beale; Avinash V. Karpe; Sonia Shastri; Waheedha Basheer; Benjamin Southam; Rajaraman Eri; et al. Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases. European Journal of Nutrition 2020, 59, 3669-3689, 10.1007/s00394-020-02200-9.
  19. Tanvi Shinde; Agampodi Promoda Perera; Ravichandra Vemuri; Shakuntla V. Gondalia; Avinash V. Karpe; David J. Beale; Sonia Shastri; Benjamin Southam; Rajaraman Eri; Roger Stanley; et al. Synbiotic Supplementation Containing Whole Plant Sugar Cane Fibre and Probiotic Spores Potentiates Protective Synergistic Effects in Mouse Model of IBD. Nutrients 2019, 11, 818, 10.3390/nu11040818.
  20. Tanvi Shinde; Ravichandra Vemuri; Sonia Shastri; Agampodi Promoda Perera; Shakuntla V. Gondalia; David J. Beale; Avinash V. Karpe; Rajaraman Eri; Roger Stanley; Modulating the Microbiome and Immune Responses Using Whole Plant Fibre in Synbiotic Combination with Fibre-Digesting Probiotic Attenuates Chronic Colonic Inflammation in Spontaneous Colitic Mice Model of IBD. Nutrients 2020, 12, 2380, 10.3390/nu12082380.
  21. Dietary Fibre from Virgin Sugarcane . Encyclopedia Scholarly Community. Retrieved 2021-3-29
  22. Amandeep Kaur; Devin J. Rose; Pinthip Rumpagaporn; John A. Patterson; Bruce R. Hamaker; In Vitro Batch Fecal Fermentation Comparison of Gas and Short-Chain Fatty Acid Production Using “Slowly Fermentable” Dietary Fibers. Journal of Food Science 2011, 76, H137-H142, 10.1111/j.1750-3841.2011.02172.x.
  23. Daniela Parada Venegas; Marjorie K. De La Fuente; Glauben Landskron; María Julieta González; Rodrigo Quera; Gerard Dijkstra; Hermie J. M. Harmsen; Klaas Nico Faber; Marcela A. Hermoso; Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Frontiers in Immunology 2019, 10, 277, 10.3389/fimmu.2019.00277.
  24. Dallas R. Donohoe; Darcy Holley; Leonard B. Collins; Stephanie A. Montgomery; Alan C. Whitmore; Andrew Hillhouse; Kaitlin P. Curry; Sarah W. Renner; Alicia Greenwalt; Elizabeth P. Ryan; et al. A Gnotobiotic Mouse Model Demonstrates That Dietary Fiber Protects against Colorectal Tumorigenesis in a Microbiota- and Butyrate-Dependent Manner. Cancer Discovery 2014, 4, 1387-1397, 10.1158/2159-8290.cd-14-0501.
More
©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback