Mechanisms of the 35624® Strain

This unique Bifidobacterium longum probiotic strain is considered to have the best evidence base for efficacy in irritable bowel syndrome (IBS). The mechanisms underlying the efficacy of the 35624® culture in IBS have been extensively studied.

    This research shows that the strain locks onto the irritated bowel to provide a calming and strengthening layer, thereby countering the impairment of gut barrier function that occurs in IBS and  reducing IBS symptoms: bloating and gas, abdominal pain, and unpredictable diarrhoea and constipation.

    The 35624® strain:


    Arrives: Survives alive through the gut, reaching the intestines – the site of its activity.


    Binds: Adheres to the intestinal epithelial cells and mucus layer of the gut barrier.


    Calms: Reduces the disruption of the gut barrier that occurs in IBS.

    «Not all probiotics are alike. The affects are strain specific and potential health benifits can only be attributed to the strain tested.»

    The Gut Barrier

    This separates the gut lumen from the body’s internal environment. The gut barrier (Fig 1) is vital for maintaining intestinal homeostasis: it allows uptake of ions, nutrients and water into the body whilst restricting the entry of pathogens and harmful substances.3,7

    [illustrasjon] Figure 1. Components of the gut barrier
    [illustrasjon] Figure 1. Components of the gut barrier

    Commensal Bacteria and Gut Barrier Function

    Figure 2.  Electron micrograph of bifidobacteria binding to human epithelial Caco-2 cells
    Figure 2.  Electron micrograph of bifidobacteria binding to human epithelial Caco-2 cells

    Bacteria in the gut help maintain gut barrier function.17,27 Probiotic strains have also been shown to have direct effects on this.21 Evidence of the ability of bifidobacteria (including B. longum strains) to bind to the intestinal mucosa first came from in vitro tests using human intestinal cell lines that are validated models of the human colon: Caco-2 and the mucus-secreting HT29-MTX (Fig 2).2,8 Bifidobacteria have also been shown to adhere to mucus and inflamed mucosa.13,15,18,28 and can use host-derived mucins as growth substrates.26 A number of adhesion factors on the surface of bifidobacteria enable them to adhere to host structures.29


    Impairment of the Gut Barrier in IBS

    Loss of the integrity of the intestinal epithelium increases intestinal permeability (Fig 4a), which is seen in many IBS patients, particularly those with IBS-D. 3,19 Increased intestinal permeability (sometimes called ‘leaky gut syndrome’) has been linked to diarrhoea, low-grade inflammation and increasing severity of disease and visceral hypersensitivity in IBS. 4,11,12,19

    Visceral hypersensitivity (a lower pain threshold) is observed in most IBS patients. 10 Compared to healthy people, patients experience more pain during episodes of bloating, flatulence or intestinal dysfunction, regardless of IBS subtype.

    Certain IBS risk factors are also risks for intestinal dysbiosis (e.g. stress, dietary ingredients, antibiotics and infectious diarrhoea) and the profile of the faecal microbiota of people with IBS can differ from that of healthy people.11,25 Differences in the composition of mucosa-adherent bacteria have also been observed.22 In IBS, disruption of the gut microbiota composition contributes to the dysregulation of gut barrier function that occurs in this disease.22

    Impairment of the Gut Barrier in IBS

    Loss of the integrity of the intestinal epithelium increases intestinal permeability (Fig 4a), which is seen in many IBS patients, particularly those with IBS-D. 3,19 Increased intestinal permeability (sometimes called ‘leaky gut syndrome’) has been linked to diarrhoea, low-grade inflammation and increasing severity of disease and visceral hypersensitivity in IBS. 4,11,12,19

    Visceral hypersensitivity (a lower pain threshold) is observed in most IBS patients. 10 Compared to healthy people, patients experience more pain during episodes of bloating, flatulence or intestinal dysfunction, regardless of IBS subtype.

    Certain IBS risk factors are also risks for intestinal dysbiosis (e.g. stress, dietary ingredients, antibiotics and infectious diarrhoea) and the profile of the faecal microbiota of people with IBS can differ from that of healthy people.11,25 Differences in the composition of mucosa-adherent bacteria have also been observed.22 In IBS, disruption of the gut microbiota composition contributes to the dysregulation of gut barrier function that occurs in this disease.22

    Figure 3. Altered visceral pain perception in IBS patients (blue) compared to healthy people (green) 20
    Figure 3. Altered visceral pain perception in IBS patients (blue) compared to healthy people (green)20
    Figure 4a.  Impairment of the gut barrier in IBS and Figure 4b. Calming effect of the 35624® strain

    The 35624® culture: effects on the gut barrier in IBS and Clinical Evidence

    The 35624® culture tackles symptoms of IBS by locking onto the irritated bowel and providing a calming and strengthening layer, countering the impairment of gut barrier function that occurs in IBS (Fig 4b) and reducing symptoms of bloating and gas, abdominal pain, and unpredictable diarrhoea and constipation. Key evidence for these effects are:


    Arrives: Clinical trials showing survival of the 35624® strain through the gut.


    Binds: Biopsies and lab studies showing live cells of the 35624® strain binding to gut cells


    Calms: Clinical trials showing that the 35624® strain reduces symptoms of IBS

    Evidence for the 35624® strain

    Arrives

    • Human intervention studies showing survival of 35624® through the gut (Fig 5).6,16,23,28 The strain was detected at levels up to 108 CFU/g in faeces. 
    • Production of an exopolysaccharide (EPS) layer, which helps protect the bacteria during transit through the gut to reach the colon alive and may contribute to gut barrier function.1,5
    Figure 5. Survival of the 35624® culture through the gut.16

    Binds

    • Isolation of the 35624® strain directly from the epithelium of a healthy human terminal ileum.21 Laboratory tests showed that the strain was tightly bound to the intestinal cells.9
    • Direct observation of 35624® cells binding to intestinal cell lines (HT-29 and Caco-2) in vitro by direct observation. The 35624® cells were confirmed as viable (Fig 6).14
    • Demonstration of the binding of 35624® to an inflamed colonic mucosa in vivo, and recovery of live cells from colonic biopsies from ulcerative colitis patients and a control.28
    Figure 6. Adherence of 35624® to human epithelial cells 14


    Calms

    • Large scale placebo-controlled, randomised trials showing significant benefit for IBS patients associated with the 35624® strain (Fig 7). 23, 30
    • The 35624® strain showed significant improvement (compared to placebo) for
      • Abdominal pain/discomfort
      • Passage of gas
      • Bloating/distension
      • Significantly better global IBS symptom relief.
    Figure 7. Clinical study: 35624® intervention associated with reduction of IBS symptoms 30

    References:
    1. Altmann F. et al. (2016) PLoS One 11(9), e0162983.
    2. Bernet M.F. et al. (1993) Applied & Environmental Microbiology 59, 4121-8.
    3. Bischoff S.C., et al. (2014) BMC Gastroenterology 14, 189.
    4. Camilleri M. et al. (2012) American Journal of Physiology-Gastrointestinal & Liver Physiology 303, G775-G785.
    5. Castro-Bravo N. et al. (2018) Frontiers in Microbiology 9, 2426.
    6. Charbonneau D. et al. (2013). Gut Microbes 4, 201-211.
    7. Chelakkot C. et al. (2018) Experimental & Molecular Medicine 50, 103.
    8. Crociani J. et al. (1995) Letters in Applied Microbiology 21, 146-148.
    9. Dunne C. et al. (1999) Antonie Van Leeuwenhoek 76(1-4), 279-92.
    10. Farzaei M.H. et al. (2016) Journal of Neurogastroenterology & Motility 22, 558-574.
    11. Foxx-Orenstein A.E. (2016) Therapeutic Advances in Gastroenterology 9, 354-375.
    12. Fukui H. (2016) Inflammatory Intestinal Diseases 1, 135-145.
    13. González-Rodriguez I. et al. (2012) Applied & Environmental Microbiology 78, 3992-3998.
    14. Groeger D. (2018) GI adherence of Bifidobacterium infantis 35624 in vitro. PrecisionBiotics Internal Report.
    15. He F. et al. (2001) Microbiology & Immunology 45, 259-262.
    16. Healy S. et al. (2017) Gut 66, A25.
    17. Hiipala K. et al. (2018) Nutrients 10, pii E988.
    18. Izquierdo E. et al. (2008) Current Microbiology 56, 613-618.
    19. Martinez C. et al. (2014) Gut & Liver 6, 305-315.
    20. Mertz H. et al. (1999) American Journal of Gastroenterology 94,609-615.
    21. Ohland C.L. & McNaughton W.K. (2010) American Journal of Physiology-Gastrointestinal & Liver Physiology 298, G807-G819.
    22. Ohman L. et al. (2015) Nature Reviews in Gastroenterology & Hepatology 12, 36-49.
    23. O’Mahony L. et al. (2005) Gastroenterology 128(3), 541-51.
    24. Quigley E.M.M. et al. (2016) Journal of Clinical Gastroenterology 50, 704-713.
    25. Quigley E.M.M. et al. (2018) Journal of Clinical Medicine 7, 6.
    26. Tailford L.E. et al. (2015) Frontiers in Genetics 6, 81.
    27. Ulluwishewa D. et al. (2011) Journal of Nutrition 141, 769-776.
    28. Von Wright A. et al. (2002) International Dairy Journal 12,197-200.
    29. Westermann C. et al. (2016) Frontiers in Microbiology 7, 1220.
    30. Whorwell P.J. et al. (2006) American Journal of Gastroenterology 101, 1581-90.