Is there a potential adjunct role for probiotics in IBD management?

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Environmental exposures linked to an increased risk of IBD include smoking in CD, childhood antibiotic exposure, non-steroidal drugs, stress, and the hygiene hypothesis (childhood exposure to germs and certain infections helps the immune system develop). Protective factors include smoking in UC, appendectomy, and breastfeeding. 

The global prevalence of IBD is estimated to be around 0.3%. The prevalence of IBD has been steadily increasing in developing countries since the 1950s, but since the 1990s, the prevalence has stabilised and even decreased in some of these countries. However, since then it has again started to increase steadily. It is predicted that the prevalence of IBD may rise to 0.9% by 2025 in developing countries. 

At the same time as decreases in developing countries were reported (1990s), IBD prevalence has started to increase in developing countries in Africa, Asia, and South America.

Some of the reasons for the increase in developing countries include dietary changes, including increased exposure to processed food, refined sugars, dairy and less plant-based fibres.

A recent South African study (2021) conducted at a tertiary colorectal unit in KwaZulu-Natal showed that Indian and White populations have the highest disease burden IBD (59% and 22%, respectively), followed by African (12%-18%). 

IBD affects men and women equally, with peak incidence between 20- and 30-years and then again from 50- to 60-years. IBD is associated with multiple complications. An estimated 50% of patients present with extra-intestinal complications such as arthropathy, metabolic bone disease, ocular, dermatological, neurologic, cardiovascular, pulmonary, urological and hepatobiliary (30% of patients present with abnormal liver tests and 5% develop chronic liver disease) complications.

The majority of healthcare costs associated with UC and CD are driven by medication. Despite the efficacy of advances in medical therapy, up to 45% of patients with UC and up to 61% of patients with CD will require surgical intervention at some point. Postoperative mortality and potential for malignant transformation are higher for UC.

Repetitive episodes of GI tract inflammation 

The hallmark of IBD is repetitive episodes of inflammation of the GI tract caused by an abnormal immune response to gut microflora. UC involves diffused inflammation of the colonic mucosa. Most often UC affects the rectum (proctitis), but it may extend into the sigmoid (proctosigmoiditis), beyond the sigmoid (distal UC), or include the entire colon up to the cecum (pancolitis). 

UC can be divided into:

  • Ulcerative proctitis 
  • Left-sided colitis 
  • Sub-total colitis 
  • Pancolitis. 

The severity of UC is determined by symptoms, findings on physical examination and laboratory tests. With spontaneous healing or treatment, UC can become inactive or quiescent. Inactive UC is characterised by marked architectural abnormalities in the absence of active inflammation.11 

CD results in transmural ulceration of any portion of the GI tract, most often affecting the terminal ileum and colon. Both diseases are classified by extent (mild, moderate, or severe) and location. CD also is classified by phenotype- inflammatory, structuring, or penetrating.

The World Gastroenterology Organization symptoms for IBD include: 

  • Diarrhoea may be associated with blood or mucus and may also occur at night and faecal incontinence is not uncommon 
  • Some patients with UC may present with constipation when the disease is localised to the rectum 
  • Abdominal pain, tenesmus, and severe urgency are also common presentations 
  • CD can present with right lower quadrant pain and UC may present with left lower quadrant pain 
  • Nausea and vomiting are more common in CD. 

Probiotics in IBD management 

Probiotics are living non-pathogenic microorganisms, which, when given in sufficient amounts (at least 106 viable CFU/g) may be beneficial to the host by improving the microbial balance in the gut and aid in metabolism. 

The strongest evidence supporting the use of probiotics as adjunct therapy treatment of GI diseases. According to Cai et al, based on the theory that IBD is caused by an abnormal immune response to gut microflora, researchers have shown that probiotics may potentially be as effective in treating GI diseases as pharmacotherapy. 

IBD symptoms can be improved by addressing intestinal microecology using all the biotics – antibiotics, probiotics, prebiotics, postbiotics and synbiotics – as well as faecal microbiota transplantation.

Probiotic properties 

Probiotics are known to have particular properties such as resistance to acid pH, bile tolerance, tolerance to pancreatic fluid, adhesion, and invasion capacity in the intestinal epithelial cells. The above properties permit their survival in the GI tract and the improvement of the intestinal balance.

Probiotic microorganisms that have been shown to have beneficial properties include Lactobacillus spp., Bifidobacterium spp., Saccharomyces boulardii, Propionibacterium spp., Streptococcus spp., Bacillus spp., Enterococcus spp. and some specific strains of Escherichia coli. 

Lactobacillus spp. are one of the most widely used probiotics. The genus Lactobacillus comprises a group of Gram-positive, nonsporulating, facultative anaerobic bacteria which include L. acidophilus, L. rhamnosus, L. bulgaricus, L. casei, and L. reuteri. L. reuteri has been shown to be one of the truly indigenous bacteria of the human GI tract. 

According to Mu et al, there are some prerequisites for becoming potential probiotics: to survive in low pH and enzyme-enriched environments, to adhere to epithelium for host-probiotic interaction, competition with pathogenic microorganisms, and most importantly, safety. L. reuteri meets all of these requirements because it normally colonises the GI tract.

Evidence support use in UC 

Studies and preclinical results have shown that Lactobacilli may help in the prevention and treatment of numerous GI tract disorders. In IBD, the evidence supports a role for the use of probiotics as adjunct therapy in patients with mild to moderate UC, but whether these agents are effective in CD, is still debated. 

Other GI disorders that benefit from probiotic supplementation include enteric infections, antibiotic-associated diarrhoea, necrotising enterocolitis in preterm neonates, colorectal cancer and irritable bowel syndrome.

The relapse rate of patients treated with mesalazine is around 20%. Some studies have shown that probiotics may be effective in inducing remission in active UC and may be as effective as 5-aminosalicylic acid (5- ASA) drugs to prevent relapse in patients with quiescent UC. 5-ASA is the mainstay to prevent relapse of quiescent UC. 

Zocco et al evaluated the efficacy of Lactobacilli alone or in combination with mesalazine (5-ASA) and mesalazine as maintenance treatment in UC.

Disease activity was measured at zero, six and 12 months. The primary endpoint was to evaluate sustained remission.

They found that there were no differences in relapse rates at six and 12 months between the three treatment groups. However, treatment with Lactobacilli was more effective than standard treatment with mesalazine in prolonging relapse-free time and represent a good therapeutic option to prevent relapse. 

  • Jairath V and Feagan BG. Global burden of inflammatory bowel disease. The Lancet Gastroenterology & Hepatology, 2019. 
  • Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence, and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. The Lancet, 2017.
  • Chonco SM, Mtetwa PN, Naidoo M, et al. A fourteen-year audit of surgery for inflammatory bowel disease at a tertiary colorectal unit. S Afr J Surg, 2021.
  • Gaspar R, Branco CC, Macedo G. Liver manifestations and complications in inflammatory bowel disease: A review. World J Hepatol, 2021.
  • McDowell C, Farooq U and Haseeb M. Inflammatory Bowel Disease. StatPearls [Internet], 2022.
  • Stavropoulou E and Bezirtzoglou. Probiotics in Medicine: A Long Debate. Front Immunol, 2020.
  • Cai Z, Wang S and Li J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med, 2021.
  • Mu Q, Tavella VJ, Luo XM. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol, 2018.
  • Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther, 2017.
  • Zocco MA, Verme LZD, Cremonini F, et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Alimentary Pharmacology and Therapeutics, 2006.
  • DeRoche TC, Ziao S-Y and Lui X. Histological evaluation in UC. Gastroenterology Report, 2014.

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