Role of Bacteria in Gastrointestinal Conditions

Role of Bacteria in Gastrointestinal Conditions

Dr Samantha Coulson, Professor Luis Vitetta
Medlab Clinical Ltd

Human Anatomy Perhaps the most studied site for investigating probiotic efficacy is the gastrointestinal tract (GIT) and inflammatory conditions such as Crohn’s disease (CD), ulcerative colitis (UC) and irritable bowel syndrome (IBS). Patients diagnosed with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) have been reported to present with increased pro-inflammatory or potentially pathogenic bacterial species such as Escherichia coli,1,2 members of the genus Bacteroides3 and Enterococci; and decreased Bifidobacteria and Lactobacilli species.4,5 For example, the etiology of IBD is not fully understood, but is considered to be a T-cell-driven inflammatory response resulting from a persistent preponderance of pro- anti-inflammatory cytokine production,6 whereas, Crohn's disease (CD) is reported to be driven by an T-helper 1 (TH1) immune response7,8 that can affect any part of the GIT, i.e., from the mouth to the anus. By contrast, UC is a T-helper 2 (Th2) driven response, and is restricted to the mucosa of the colon and rectum.8,9


Role of Probiotics in Gastrointestinal Conditions

It has been reported that probiotic bacteria may operate on three levels of host functionality via their metabolite production that enhances GIT and extra-intestinal activity namely by (a) interfering with the growth of pathogenic bacteria in the lumen of the GIT; (b) strengthening gut epithelial barrier function and mucosal immunity as well as mucus production; and (c) beyond the gut-brain, and heart. A series of clinical trials reviewed elsewhere10,11 that implemented various combinations of probiotic species frequently demonstrated efficacy in treating GIT conditions/diseases and various other end-organ tissues.10,11 The core notion emanating from the reviews was the administration of multi-species probiotic formulations could, in addition to improving GIT function, influence numerous end-organ tissues beneficially. Furthermore, clinical studies indicate that administration of probiotic bacterial species provides efficacious results in restoring the GIT microbiome to a more balanced metabolic state. This possibly achieved in part by reducing pathogenic bacterial overgrowth and the resulting adverse localized effects that in turn affect end-organ physiology.


Role of Probiotics in IBD

Probiotics have been shown to reduce abdominal pain, discomfort, and symptom scores in patients with IBS when administered Lactobacillus acidophilus,12 Lactobacillus plantarum,13 or ProSymbioflor (a combination of E. coli DSM and Enterococcus faecalis)14 compared with a placebo (see Table 1). In contrast, Drouault-Holowacz and colleagues15 found that Bifidobacterium longum, L. acidophilus, Lactobacillus lacti and Streptococcus thermophilus were not superior to the placebo treatment for relieving disease symptoms except that of abdominal pain, due to a strong placebo effect. Further analysis of the IBS subgroups revealed that patients with changing bowel habits (alternating between constipation and diarrhea and those with short durations of symptom exacerbation and remission) reported significantly less abdominal pain with constipation-predominant IBS patients reporting improved bowel motions. These results indicate that different disease etiologies may exist between IBS subgroups and that some probiotics may be more efficient than others for treating symptoms within these subgroups. These findings also point to the need to further classify patients into relevant sub groups whenever possible for assessing the efficacy of a probiotic.


Probiotic Table

Table 1. Role of probiotics in human clinical studies on GIT disorders.


A number of studies investigating the effects of probiotics within specific sub-groups of IBS have shown the beneficial effects of probiotic supplements. Therefore, Zeng and colleagues16 first separated patients with IBS into sub groups (those with increased small bowel permeability and those with increased colonic permeability), treating diarrhea-predominant IBS patients with S. thermophilus and Lactobacillus bulgaricus, Lactobacillus bulgaricus and B. longum. The proportion of patients with increased small bowel permeability (lactulose/mannitol ratio >0.025) decreased significantly (p < 0.023) after treatment. These patients also demonstrated improved IBS scores with diminished abdominal pain and flatulence. Similarly, symptoms improved after treatment with the probiotic VSL#3 in subjects with either diarrhea-predominant IBS17 or IBS with bloating.18 In subjects complaining of IBS with bloating, the VSL#3 reduced flatulence scores and retarded colonic transit time, without altering bowel function. In patients with diarrhea-predominant IBS, VSL#3 only relieved abdominal bloating, having no effect on mean transit measures, bowel function scores or satisfactory relief of symptoms. VSL#3 has also been shown to be superior to a placebo in children with IBS. VSL#3 supplementation improved overall IBS symptoms as assessed by abdominal pain/discomfort, abdominal bloating/gassiness, and on family life disruption.


Conclusion

It is therefore evident, that a multi-species probiotic consisting of multiple species from the genera of Lactobacillus, Bifidobacteria, Streptococcus and Saccharomyces demonstrates numerous therapeutic effects in relieving symptomologies associated with IBS and UC, with limited evidence for their use in CD.



References

  1. Mylonaki M, Rayment NB, Rampton DS et al (2005) Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease. Inflamm Bowel Dis 11 (5):481–487.
  2. Martin HM, Campbell BJ, Hart CA et al (2004) Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer. Gastroenterology 127:80–93.
  3. Swidsinski A, Ladhoff A, Pernthaler A et al (2002) Mucosal flora in inflammatory bowel disease. Gastroenterol 122(1):44–54.
  4. Giaffer MH, Holdsworth CD, Duerden BI (1991) The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique. J Med Microbio 35 (4):238–243.
  5. Van de Merwe JP, Schroder AM, Wensinck F et al (1988) The obligate anaerobic faecal flora of patients with Crohn’s disease and their first-degree relatives. Scand J Gastroenterol 23 (9):1125–1131.
  6. Hvas CL, Kelsen J, Agnholt J et al (2007) Crohn’s disease intestinal CD4+ T cells have impaired interleukin-10 production which is not restored by probiotic bacteria. Scand J Gastroenterol 42 (5):592–601.
  7. Matsuoka K, Inoue N, Sato T et al (2004) T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn’s disease. Gut 53(9):1303–1308.
  8. Fuss IJ, Neurath M, Boirivant M et al (1996) Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157(3):1261–1270.
  9. Heller F, Florian P, Bojarski C et al (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterol 129(2):550–564.
  10. Vitetta L, Briskey D, Alford H, Hall S, Coulson S (2014a) Probiotics, prebiotics and the gastrointestinal tract in health and disease. Inflammopharmacology 22(3):135–154.
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  12. Sinn DH, Song JH, Kim HJ et al (2008) Therapeutic effect of Lactobacillus acidophilus-SDC 2012, 2013 in patients with irritable bowel syndrome. Dig Dis Sci 53(10):2714–2718.
  13. Niedzielin K, Kordecki H, Birkenfeld B (2001) A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299 V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol 13(10):1143–1147.
  14. Enck P, Zimmermann K, Menke G et al (2008) A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome–a randomized controlled trial with primary care physicians. Neurogastroenterol Motil 20 (10):1103–1109.
  15. Drouault-Holowacz S, Bieuvelet S, Burckel A et al (2008) A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol 32(2):147–152.
  16. Zeng J, Li YQ, Zuo XL et al (2008) Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable Bowel syndrome. Aliment Pharmacol Ther 28(8):994–1002.
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  18. Kim HJ, Vazquez Roque MI, Camilleri M et al (2005) A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 17(5):687–.

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