Best probiotics for crohns. Best Probiotics for Crohn’s Disease: Evidence-Based Insights on IBD Management
What are the most effective probiotics for Inflammatory Bowel Disease. How do probiotics impact gut health in Crohn’s Disease and Ulcerative Colitis. Which probiotic strains show promise in managing IBD symptoms.
Understanding Inflammatory Bowel Disease: Crohn’s Disease vs. Ulcerative Colitis
Inflammatory Bowel Disease (IBD) is a term that encompasses two primary conditions: Crohn’s Disease (CD) and Ulcerative Colitis (UC). While these conditions share some common symptoms, such as diarrhea, blood or mucus in stools, and intestinal inflammation, they differ in the location of ulceration and tissue damage.
Ulcerative Colitis typically affects only the colon, whereas Crohn’s Disease can impact any part of the gastrointestinal tract, from mouth to anus. This distinction is crucial when considering probiotic interventions, as different bacteria inhabit various areas of the intestinal tract and have diverse mechanisms of action.
Subtypes of Crohn’s Disease
- Ileocolitis: Affects the ileum and colon
- Ileitis: Solely affects the ileum
- Gastroduodenal Crohn’s disease: Impacts the stomach and duodenum
- Jejunoileitis: Affects the jejunum
- Crohn’s colitis: Limited to the colon
The prevalence of IBD is significant, with an estimated 1 in every 250 people in the UK affected by these conditions. This high incidence rate underscores the importance of understanding and effectively managing IBD.
The Role of Gut Microbiota in IBD Pathogenesis
Research has long hypothesized that alterations in intestinal bacterial flora may contribute to the onset and progression of IBD. This theory is now supported by clinical evidence, as several studies have found significant differences in the composition of gut flora between IBD patients and healthy individuals.
How does the gut microbiome differ in IBD patients? Multiple studies have observed higher numbers of anaerobic bacteria in fecal samples from Crohn’s disease patients compared to healthy controls, with particularly elevated levels of Bacteroides. Other research has found increased levels of aerobes and Enterobacteria in active Crohn’s disease, along with decreased Lactobacilli populations.
While the specific bacterial imbalances may vary between studies, the consistent observation of dysbiosis in IBD patients supports the theory that intestinal flora plays a crucial role in the pathogenesis of these conditions. This understanding has led researchers to investigate the potential benefits of probiotic supplementation in managing IBD symptoms.
Probiotics and Crohn’s Disease: Promising Research Findings
One of the most extensively studied probiotic strains in relation to Crohn’s disease is a non-pathogenic strain of E. coli known as E. coli Nissle 1917. A landmark double-blind study conducted in 1997 by Malchow investigated the effects of this probiotic strain on patients with active Crohn’s disease.
What were the results of this study? The research found that while remission rates were similar between the probiotic and placebo groups (both receiving standard steroid treatment), the subsequent relapse rates were significantly lower in the E. coli treated group. Specifically, 33% of patients in the probiotic group experienced a relapse, compared to 64% in the placebo group.
These findings suggest that while E. coli Nissle 1917 may not enhance the initial achievement of remission when combined with standard steroid treatment, it may play a crucial role in maintaining remission and preventing symptom recurrence in Crohn’s disease patients.
Exploring Other Probiotic Strains for IBD Management
While E. coli Nissle 1917 has shown promise, it’s important to note that other strains of E. coli can be pathogenic. Therefore, practitioners should exercise caution and await further research before recommending E. coli-based supplements. Fortunately, other probiotic strains have also been investigated for their potential benefits in IBD management.
Lactobacillus and Bifidobacterium Strains
Several studies have explored the effects of Lactobacillus and Bifidobacterium strains on IBD symptoms. These genera are commonly found in many commercial probiotic supplements and are generally considered safe for consumption.
A randomized, double-blind, placebo-controlled trial investigated the effects of a probiotic mixture containing Lactobacillus casei, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, and Streptococcus salivarius subsp. thermophilus on patients with Crohn’s disease in remission.
What were the outcomes of this study? The results showed that the probiotic mixture was effective in maintaining remission in Crohn’s disease patients. After 12 months, 73% of patients in the probiotic group remained in remission, compared to only 33% in the placebo group.
Probiotics and Ulcerative Colitis: A Different Perspective
While the research on probiotics for Crohn’s disease has yielded mixed results, studies focusing on Ulcerative Colitis have shown more consistent positive outcomes. This difference may be attributed to the localized nature of UC, which primarily affects the colon where many probiotic strains exert their effects.
A systematic review and meta-analysis of 23 randomized controlled trials found that probiotics were effective in inducing remission in patients with active UC. The analysis showed that probiotics were significantly more effective than placebo in achieving clinical remission, with a relative risk of 1.51.
VSL#3: A Multi-Strain Probiotic for UC
One probiotic preparation that has shown particular promise in managing Ulcerative Colitis is VSL#3. This high-potency, multi-strain probiotic contains eight different bacterial strains: Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, and Streptococcus thermophilus.
How effective is VSL#3 in managing UC symptoms? A double-blind, randomized controlled trial found that 77% of UC patients who received VSL#3 in addition to standard therapy achieved remission, compared to only 33% in the placebo group. Furthermore, the probiotic group experienced a significant reduction in disease activity scores and an improvement in rectal bleeding.
Mechanisms of Action: How Probiotics May Benefit IBD Patients
Understanding the potential mechanisms by which probiotics exert their beneficial effects in IBD is crucial for optimizing their use in clinical practice. Several hypotheses have been proposed to explain the positive impact of probiotics on gut health in IBD patients.
1. Enhancing the Intestinal Barrier Function
Probiotics may help strengthen the intestinal barrier, which is often compromised in IBD. They can achieve this by:
- Increasing the production of mucus
- Enhancing the expression of tight junction proteins
- Promoting the secretion of antimicrobial peptides
2. Modulating the Immune Response
Certain probiotic strains have been shown to influence the immune system, potentially reducing inflammation in the gut. This may occur through:
- Increasing the production of anti-inflammatory cytokines
- Decreasing pro-inflammatory cytokines
- Regulating T-cell responses
3. Competing with Pathogenic Bacteria
Probiotics can help maintain a healthy balance of gut microbiota by:
- Competing for adhesion sites on the intestinal epithelium
- Producing antimicrobial substances
- Consuming nutrients that would otherwise be available to pathogens
Selecting the Right Probiotic for IBD Patients
When considering probiotic supplementation for IBD patients, it’s essential to take an individualized approach. The choice of probiotic strain or combination of strains should be based on the specific type of IBD, the location of inflammation, and the patient’s overall health status.
Factors to Consider When Choosing a Probiotic
- Strain specificity: Different probiotic strains have varying effects on gut health. Choose strains that have been specifically studied for the type of IBD in question.
- Dosage: Ensure that the probiotic supplement contains an adequate number of colony-forming units (CFUs) to exert a therapeutic effect.
- Quality and viability: Select products from reputable manufacturers that guarantee the potency and viability of the probiotic strains through the end of shelf life.
- Potential interactions: Consider any medications the patient is taking and potential interactions with probiotic supplementation.
- Patient preferences: Take into account factors such as dietary restrictions, allergies, and preferred dosage forms (capsules, powders, liquids).
How can healthcare providers determine the most suitable probiotic for their IBD patients? It’s advisable to stay up-to-date with the latest research and consult with specialists in gastroenterology and nutrition. Additionally, starting with well-studied strains or combinations, such as VSL#3 for Ulcerative Colitis, may be a prudent approach.
Integrating Probiotics into a Comprehensive IBD Management Plan
While probiotics show promise in managing IBD symptoms, it’s crucial to view them as part of a holistic treatment approach rather than a standalone solution. Integrating probiotic supplementation with other evidence-based interventions can potentially enhance outcomes for IBD patients.
Complementary Strategies for IBD Management
- Dietary modifications: Implementing specific diets, such as the low FODMAP diet or the Specific Carbohydrate Diet, may help alleviate symptoms in some IBD patients.
- Stress reduction techniques: Practices like mindfulness meditation or cognitive-behavioral therapy can help manage stress, which is known to exacerbate IBD symptoms.
- Regular exercise: Moderate physical activity has been shown to have anti-inflammatory effects and may improve overall well-being in IBD patients.
- Adequate sleep: Ensuring sufficient, quality sleep can support immune function and help manage inflammation.
- Nutritional supplementation: Addressing potential nutrient deficiencies common in IBD, such as vitamin D, iron, or B12, may be necessary.
How can healthcare providers effectively incorporate probiotics into a comprehensive IBD management plan? It’s essential to take a patient-centered approach, considering individual needs, preferences, and lifestyle factors. Regular follow-ups and assessments can help determine the effectiveness of the probiotic intervention and make necessary adjustments to the overall treatment plan.
Future Directions in Probiotic Research for IBD
As our understanding of the gut microbiome and its role in IBD continues to evolve, so too does the potential for developing more targeted and effective probiotic interventions. Several exciting areas of research are currently being explored that may shape the future of probiotic use in IBD management.
1. Personalized Probiotic Therapies
Advances in microbiome sequencing and analysis are paving the way for more personalized approaches to probiotic supplementation. By analyzing an individual’s gut microbiome composition, researchers hope to develop tailored probiotic formulations that address specific microbial imbalances associated with IBD.
2. Engineered Probiotics
Scientists are exploring the potential of genetically engineered probiotics designed to deliver specific therapeutic compounds directly to the gut. For example, probiotics could be engineered to produce anti-inflammatory molecules or growth factors that promote intestinal healing.
3. Synbiotics: Combining Probiotics and Prebiotics
Research is ongoing into the potential benefits of synbiotics – combinations of probiotics and prebiotics – in managing IBD. The idea is that the prebiotic component can selectively nourish the beneficial probiotic bacteria, potentially enhancing their colonization and therapeutic effects.
4. Novel Probiotic Strains
As our understanding of the gut microbiome expands, researchers are identifying new bacterial strains with potential probiotic properties. Some of these novel strains may prove to be more effective in managing IBD symptoms than currently available probiotics.
What challenges need to be addressed in future probiotic research for IBD? Some key areas for improvement include:
- Standardization of probiotic preparations and dosages across studies
- Larger, well-designed clinical trials with longer follow-up periods
- Better understanding of the mechanisms of action of specific probiotic strains in IBD
- Investigation of potential long-term effects and safety profiles of probiotic supplementation in IBD patients
As research in this field progresses, it’s likely that we’ll see more targeted and effective probiotic interventions for IBD management. Healthcare providers should stay informed about these developments to provide the best possible care for their patients with Crohn’s disease and Ulcerative Colitis.
Which probiotics are best for IBD?
Digestive Health
Kathy Wheddon
Nutritional Therapist DipION
Before we start to look at the evidence behind the use of probiotics in Inflammatory Bowel Disease (IBD), it is important to understand the two different types of IBD, and their clinical presentations. Both Crohn’s Disease (CD) and Ulcerative Colitis (UC) share some similarities in symptoms, such as diarrhoea, blood* or mucus in the stools and inflammation and damage to the intestinal wall. However, the defining difference between the two conditions is the location of the ulceration and/or tissue damage. Typically, ulceration in Ulcerative Colitis is limited to the colon, whereas in Crohn’s Disease the damage can occur at any point in the GI tract, from the mouth to the anus. Crohn’s Disease is therefore divided in to 5 sub-types, dependent on the exact location in the GI tract that the damage is located.
• Ileocolitis: affects the ileum and the colon
• Ileitis: solely affects the ileum
• Gastroduodenal Crohn’s disease: affects the stomach and duodenum
• Jejunoileitis: affects the jejunum
• Crohn’s colitis: affects only the colon
It is estimated that IBD affects 1 person in every 250 in the UK
The different site of damage in the various forms of IBD is important when considering probiotic administration, as different bacteria live in different areas of the intestinal tract, and have different mechanisms of action. For this reason, most clinical trials looking at the potential for probiotic supplementation in Inflammatory Bowel Disease, focus on either Ulcerative Colitis or Crohn’s Disease, rather than grouping them both together.
Additionally, there are many other conditions affecting the GI tract that have an inflammatory component to them, however they are not typically classified as IBD. Such conditions would include Coeliac Disease, and Diverticula Disease.
Intestinal flora of IBD patients
It has been hypothesised for many years that alterations to the intestinal bacterial flora may contribute to the onset and progression of IBD. This is a theory that is now supported by clinical evidence, as several different research studies have found the composition of gut flora to be very different in IBD patients to healthy control patients. Three separate trials1,2,3all found greater numbers of anaerobic bacteria in faecal samples taken from Crohn’s disease patients than in healthy controls, with particularly elevated levels of Bacteroides.
Contrary to these studies, Giaffer et al4 found no difference in total anaerobes between active CD patients, inactive CD patients and healthy controls, but they did find more aerobes and Enterobacteria in active CD, and fewer Lactobacilli in CD patients than healthy controls.
Other research groups have focused their studies into the presence of possible pathogens in IBD, such as bacteria from the Mycobacteria and Listeria genus.
To date, the results from many of these studies are difficult to interpret and often contradictory. Imbalances in gut flora are generally found, supporting the theory that intestinal flora contributes to the pathogenesis of IBD, but the bacterial species involved often differs.
Understanding however, that dysbiosis is almost always observed in IBD patients is a step forward, even if the exact mechanics are not yet fully understood. As a logical progression from this finding, researchers have started to review the clinical outcomes of using different strains of probiotic bacteria and/or yeast in IBD patients and animal models of IBD.
So we have already looked at the increased prevalence of disruption to the GI flora in Crohn’s Disease and Ulcerative Colitis patients, as compared to healthy individuals, now let’s consider whether probiotics may help to support gut health for your clients.
Probiotics and Crohn’s disease
A non-pathogenic strain of E.coli (E. Coli Nissle 1917) has been one of the most clinically trialled probiotics with regard to Crohn’s disease. In a 1997 double-blind study by Malchow5 E.Coli Nissle 1917 or placebo was taken daily for twelve months by 32 patients with active Crohn’s disease. Both groups also received standard steroid treatment at the same time. The results showed that whilst remission rates were similar for both groups (suggesting no additional benefit to adding the probiotic to standard steroid treatment) the subsequent relapse rates were lower in the E.coli treated group (33% relapse versus 64%). This means that once remission had been achieved less of the probiotic group re-developed symptoms. Whilst this particular strain of E. coli has shown probiotic potential, we would suggest practitioners wait for more research before seeking out any E. coli supplements, as of course other strains of this bacteria are well documented and widely known for their pathogenic effect on the human body. E. coli does not appear on the European Food Safety Authority’s Qualified Presumption of Safety (QPS) list.
Saccharomyces boulardii strain
The well researched probiotic yeast Saccharomyces boulardii has also been extensively trialled in Crohn’s disease sufferers. In 2000, Guslandi et al6 divided 32 CD patients into two groups, and gave one group 1g of an anti-inflammatory drug used to treat IBD three times daily, and the other group 1g of the same drug twice daily in combination with S. boulardii probiotic, at a daily dose of 20 Billion CFU (split between 4 capsules). Over the course of 6 months, only one of the 16 patients taking 4 capsules of S. boulardii a day suffered a flare-up of their symptoms. Of the 16 patients from the control group, that were solely given the anti-inflammatory drug, 6 patients experienced a flare-up.
The fact that the relapse rate was significantly lower in patients treated with the drug in combination with S. boulardii, suggests a protective effect from the probiotic.
Probiotics and Ulcerative Colitis
The same strain of non-pathogenic E.coli (E.coli Nissle1917) as was trialled in Crohn’s Disease has also been extensively trialled in Ulcerative Colitis. This strain of bacteria has been compared with an anti-inflammatory drug used to treat IBD in three separate studies of UC patients. Perhaps the most conclusive of them, by Kruis et al7, showed that out of the 327 study participants, that were treated with either E.Coli Nissle1917 or 500mg of the drug three times daily, the relapse rates were similar in both groups, indicating that E.Coli Nissle1917 may be as effective as anti-inflammatory drugs in preventing relapse in UC patients.
A multi-strain probiotic formulation has also been studied for UC. The combination product that was researched, contained three strains of Bifidobacteria, four of Lactobacilli and one of Streptococcus salivarius sp. thermophilus. In this study by Venturi et al8 twenty patients with inactive Ulcerative Colitis were given the probiotic formulation daily for a twelve month period, during which time remission was maintained in 15 out of the 20 study participants. Whilst a 75% success rate appears significant, this trial was not placebo-controlled, so it is difficult to draw any true conclusions.
Saccharomyces boulardii has also been studied in a small pilot study involving 25 Ulcerative Colitis patients that were experiencing a flare up of their condition. Ordinarily steroid treatment would be given in such a situation, however all 25 of these UC patients had had negative reactions to steroids in the past. In this study by Guslandi et al9 all 25 patients were given 250mg S. boulardii three times per day for four weeks, alongside their regular anti-inflammatory drug treatment. 17 out of the 25 patients achieved clinical remission in this time, as confirmed by endoscopic examination. Whilst this study lacked a control group, and was quite small in number, the results definitely warrant further study, and look promising at this stage.
In 2021 the probiotic strain Lactobacillus plantarum HNU082 (Lp082) was investigated and found to play a protective role in Ulcerative Colitis in mice10. At present no human trials have been undertaken using Lactobacillus plantarum HNU082 (Lp082).
Key takeaways of probiotics and IBD
I often seem to write this line, but rarely is it more true than here, that more research is needed to determine the best strains of probiotic to use in this group of patients. Some promising findings have been uncovered already, and I personally am particularly excited about the potential role of Saccharomyces boulardii in helping to support gut health in both Ulcerative Colitis and Crohn’s Disease. Saccharomyces boulardii is my absolute favourite probiotic, as it has so many varied clinical applications.
I eagerly await further research in to this field, and in the interim I think that healthcare professionals can feel excited about the potential for probiotics in IBD management.
To add more targeted support and to benefit from potent anti-inflammatory effects, Saccharomyces boulardii can be used as maintenance for IBD patients. Some clinical trials into the use of this supplement suggest that patients are less likely to suffer a flare up of their symptoms if they add Saccharomyces boulardii to their existing plan. Additionally, many IBD sufferers experience frequent bouts of diarrhoea as a symptom of their disease, and Saccharomyces boulardii has been especially clinically trialled and shown to support bowel health in those with occasional diarrhoea.
You can find Saccharomyces boulardii in Optibac Probiotics Saccharomyces Boulardii.
For any practitioners working with Crohn’s Disease patients, you may be interested to read fellow Nutritional Therapist Kerry’s article, about the effect of pharmaceutical Crohn’s treatments on the gut flora: New study explores effects of Crohn’s treatments on gut flora.
* NB: We do not recommend probiotics be taken by patients with blood in the stool without first consulting their doctor. More information on safety here, in the Probiotics Learning Lab.
You can read more about the studies on Saccharomyces boulardii over on the Probiotics Database.
References
- Roediger WEW, Duncan A, Kapaniris O, Miljard S. Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology 1993;104: 802-9 [PubMed]
- Ruseler-van Embden JGH, Both-Patoir HC. Anaerobic Gram-negative faecal flora in patients with Crohn’s disease and healthy subjects. Ant Leeuwenhoek 1983;49: 125-32 [PubMed]
- Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in inflammatory bowel disease.Gastroenterology 2002;122: 44-54 [PubMed]
- Giaffer MH, Holdsworth CD, Duerden BI. The assessment of faecal flora in patients with inflammatory bowel diseases by a simplified bacteriological technique. J Med Microbiol 1991;35: 238-43 [PubMed]
- Malchow HA. Crohn’s disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn’s disease. J Clin Gastroenterol 1997;25: 653-8 [PubMed]
- Guslandi M, Mezzi G, Sorghi M, Testoni PA. Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 2000;45: 1462-4 [PubMed]
- Kruis W, Fric P, Stolte M. Maintenance of remission in ulcerative colitis is equally effective with Escherichia coli Nissle 1917. Gastroenterology 2001;120(suppl 1): A127
- Venturi A, Gionchetti P, Rizzelo F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999;13: 1103-8 [PubMed]
- Guslandi, M. et al. (2003) A pilot trial of Saccharomyces boulardii in ulcerative colitis. European Journal of Gastroenterology & Hepatology. Vol. 15 pp. 697 – 698.
- Yuqing Wu et al. , (2022) Probiotics (Lactobacillus plantarum HNU082) Supplementation Relieves Ulcerative Colitis by Affecting Intestinal Barrier Functions, Immunity-Related Gene Expression, Gut Microbiota, and Metabolic Pathways in Mice. Microbiology Spectrum, Dec 21;10(6):e0165122.
Article Updated: 11 May 2023
Originally Published: 14 Oct 2018
Probiotics for Crohn’s disease: what have we learned?
Gut. 2006 Jun; 55(6): 757–759.
doi: 10.1136/gut.2005.085381
Author information Copyright and License information Disclaimer
Probiotics do not seem to be a therapeutic option for patients with Crohn’s disease, either in the acute phase or for maintenance
Keywords: Crohn’s disease, randomised controlled trial, probiotics, lactobacillus
A causative role of bacteria in Crohn’s disease (CD) has been surmised for a long time. Only in recent years however has there been a large body of evidence from genetic and bacteriological studies indicating that the intestinal flora is the essential factor in driving the Crohn’s inflammatory process in genetically susceptible individuals. 1,2,3,4,5
The therapeutic arsenal for treating CD assumes the correctness of the above hypothesis. Thus immunosuppressors are used to reduce the host response and antibiotics are used to suppress the bacterial flora, with a consequent decreased activation of the gut immune system.6 Between the two strategies it should theoretically be better to remove the harmful cause instead of reducing the host defences by inducing a form of immunodeficiency that is susceptible to opportunistic infections.
If the intervention on the gut flora works, substituting antibiotics (which are heavily burdened by side effects) with probiotics is an appealing alternative. Probiotics are defined as a living microbial food ingredient with a beneficial effect on human health7; however, the concept that probiotics are a type of long life elixir useful in many pathological conditions needs to be viewed with caution.
In a world medical scenario, where new science develops new drugs and the financial cost increases, natural remedies, relatively cheap and potentially free from side effects, catch the consumer’s attention, thereby possibly biasing medical judgement.
To date, diverse probiotics, containing different strains and quantities of bacteria, are sold on the market.8 Their therapeutic effects may include a competitive action with commensal and pathogenic flora and an influence on the immune response through various mechanisms.9 Probiotics have been successfully employed in the treatment of antibiotic associated and Clostridium difficile diarrhoea,10,11 traveller’s diarrhoea,12 and rotavirus infection.13 For inflammatory bowel diseases (IBD), some researchers have reported success with different strains of probiotics in the treatment of ulcerative colitis,14,15 CD,16,17,18 and in pouchitis treatment and prevention.19,20E coli Nissle 1917, the yeast Saccharomyces boulardii, Lactobacillus rhamnosus strain GG (LGG), and VSL#3, a cocktail of eight different strains, are the various probiotics employed in these studies. Several significant flaws however limit the importance of many of the probiotic trials, such as inclusion of too few patients,16,17 too low a dose of the control drug,14 or the association of the probiotic with other medicines.15,16,17,18
Given their potentially high safety profile, the use of probiotics for maintaining CD remission induced by drugs or surgery is particularly appealing. It is suggested that luminal bacteria are the main cause of recurrent lesions after operation.3 Moreover, preventing recurrent lesions in CD after surgery has removed all of the macroscopic inflamed tracts is the best test for any type of drug.
Consequently, LGG, which has been shown to survive and colonise the human intestine by adhering to intestinal cells, has been challenged in two randomised placebo controlled trials for its efficacy in preventing recurrence after surgery21 and relapse after medically induced remission. 22
In the first study, 45 patients operated on for CD were randomly allocated to receive 12 billion LGG or identical placebo for one year.21 Clinical recurrence was ascertained in 16.6% on Lactobacillus and in 10.5% on placebo. Sixty per cent of patients in clinical remission on Lactobacillus had endoscopic recurrence in comparison with 35.3% on placebo. There were no significant differences in the severity of lesions between the two groups.
The second trial involved 75 children in medically induced remission.22 They were randomised to receive 1010 LGG bacteria or placebo for two years as an adjunct to standard maintenance treatment. The average time to relapse was 9.8 months in the LGG group and 11 months in the placebo group; 31% and 17% of children on LGG and placebo, respectively, relapsed during the study period. Neither study showed any statistically significant differences between the active and placebo groups.
In this issue of Gut, Marteau and colleagues23 have reported the results of a trial with Lactobacillus johnsonii (LA1) for prophylaxis of postoperative recurrence in CD (see page 842). Ninety eight adult patients were randomised in a double blind, placebo controlled study in which they received 4×109 LA1 or placebo for six months. At the end of this period, 64% of patients on placebo and 49% on probiotic had endoscopic recurrence. Endoscopic scores and clinical recurrences did not differ between the two groups.
Unfortunately, this study is neither decisively negative nor decisively positive. In fact, the lack of statistically significant difference between Lactobacillus and placebo might be due either to an insufficiently large sample size or to the follow up period of six months, which may have been too short to demonstrate a larger difference. However, the cumulative result of these three studies is not encouraging, and at the moment probiotics are not a therapeutic option for CD patients either in the acute phase or for maintenance.
Is it curtains, then, for probiotics in CD?
Before dropping the curtain we have to take into account some important points.
CD is a complex entity. Diverse locations and different disease behaviours may well condition the response to probiotics—for example, colonic location seems to respond better to antibiotics and, consequently, might be more susceptible to flora manipulation.
The course of CD follows different phases; probiotics might be more effective in the early ones.
There are many species of probiotic. One type might be more effective than another because strain specific properties might influence the efficacy in different cases and situations.
The quantity of bacterial content may condition the effectiveness of the probiotic.
In short, it seems advisable to wait for results from some larger controlled trials, some of which are already underway.
Setting aside the question of probiotic effectiveness however, is their use absolutely safe? In CD, antigenic stimuli contribute towards maintaining gut inflammation, and any bacteria can become a stimulus. In the two studies with LGG, recurrence rates were lower in the placebo groups than in the groups treated with probiotics.21,22
Moreover, some anecdotal reports of infections probably caused by probiotics have been published.24,25 Probiotic strains adhering to the intestinal mucosa could translocate, inducing bacteraemia and sepsis. This risk can be increased in patients with severe disease or deeply immunosuppressed.
So, in conclusion, is all news about probiotics in CD negative? A possible future scenario on probiotics use in this disease has come from data extrapolated from allergic paediatric patients. In children with atopic dermatitis, probiotics seem to stabilise intestinal barrier function and decrease gastrointestinal symptoms.26,27,28,29
In CD, enhanced mucosa permeability may play a pivotal role in causing and perpetuating intestinal inflammation.30 It is possible therefore that administration of probiotics in the very early phases of CD may limit pathological damage and aggravation of symptoms by stabilising the intestinal barrier.
We can also speculate that children with IBD familiarity, who are at risk of developing CD, could be treated by probiotics to reduce intestinal permeability and counterbalance the hypothetical “harmful” species. For this purpose, identification of subjects at risk of developing CD could be done by analysis of genetic characteristics, such as NO2 and other genes still to be identified. In this case, genetic studies in IBD could be promoted from the laboratory to practical usefulness.
Conflict of interest: None declared.
1. Sartor R B. Role of intestinal microflora in initiation and perpetuation of inflammatory bowel disease. Can J Gastroenterol 19904271–277. [Google Scholar]
2. Sartor R B. Enteric microflora in IBD: pathogens or commensals? Inflamm Bowel Dis 1997323–35. [PubMed] [Google Scholar]
3. Rutgeerts P, Geboes K, Peeters M.et al Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 1991338771–774. [PubMed] [Google Scholar]
4. Prantera C, Scribano M L. Crohn’s disease: the case for bacteria. Ital J Gastroenterol Hepatol 199931244–246. [PubMed] [Google Scholar]
5. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998115182–205. [PubMed] [Google Scholar]
6. Barnias G, Marini M, Moskaluk C A.et al Down‐regulation of intestinal lymphocyte activation and Th2 cytokine production by antibiotic therapy in a murine model of Crohn’s disease. J Immunol 20021695308–5314. [PubMed] [Google Scholar]
7. Gorbach S L. Probiotics and gastrointestinal health. Am J Gastroenterol 200095(suppl)S2–S4. [PubMed] [Google Scholar]
8. Faubion W A, Sandborn W J. Probiotic therapy with E. Coli for ulcerative colitis: take the good with the bad, Gastroenterology 2000118630–631. [PubMed] [Google Scholar]
9. Shanahan F. Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis 20006107–115. [PubMed] [Google Scholar]
10. Surawicz C M, Elmer G W, Speelman P.et al Prevention of antibiotic‐associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology 198996981–988. [PubMed] [Google Scholar]
11. Gorbach S L, Chang T W, Goldin B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 198721519 [PubMed] [Google Scholar]
12. Hilton E, Kolakowski P, Smith M.et al Efficacy of Lactobacillus GG as a diarrheal preventative in travelers diarrhea. J Travel Med 1996441–43. [PubMed] [Google Scholar]
13. Saavedra J M, Bauman N A, Oung I.et al Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 19943441046–1049. [PubMed] [Google Scholar]
14. Kruis W, Schutz E, Fric P.et al Double‐blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 199711853–858. [PubMed] [Google Scholar]
15. Rembacken B J, Snelling A M, Hawkey P M.et al Non‐pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999354635–639. [PubMed] [Google Scholar]
16. Malchow H A. Crohn’s disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn’s disease? J Clin Gastroenterol 199725653–658. [PubMed] [Google Scholar]
17. Guslandi M, Mezzi G, Sorghi M.et al Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 2000451462–1464. [PubMed] [Google Scholar]
18. Campieri M, Rizzello F, Venturi A.et al Combination of antibiotic and probiotic treatment is efficacious in prophylaxis of post‐operative recurrence of Crohn’s disease: a randomized controlled study vs mesalamine. Gastroenterology 2000118A781 [Google Scholar]
19. Gionchetti P, Rizzello F, Venturi A.et al Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double‐blind, placebo‐controlled trial. Gastroenterology 2000119305–309. [PubMed] [Google Scholar]
20. Gionchetti P, Rizzello F, Helwig U.et al Prohylaxis of pouchitis onset with probiotic therapy: a double blind, placebo controlled trial. Gastroenterology 20031241202–1209. [PubMed] [Google Scholar]
21. Prantera C, Scribano M L, Falasco G.et al Ineffectiveness of probiotics in preventing recurrenece after curative resection for Crohn’s disease: a randomised controlled trial with Lactobacillus GG. Gut 200251405–409. [PMC free article] [PubMed] [Google Scholar]
22. Bousvaros A, Guendalini S, Baldassano R N.et al A randomized, double blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis 200511833–839. [PubMed] [Google Scholar]
23. Marteau P, Lémann M, Seksik P.et al Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial. Gut 200655842–847. [PMC free article] [PubMed] [Google Scholar]
24. Riquelme A J, Calvo M A, Guzman A M.et al Saccharomyces cerevisiae fungemia after Saccharomyces boulardii treatment in immunocompromised patients. J Clin Gastroenterol 20033641–43. [PubMed] [Google Scholar]
25. De Groote M A, Frank D N, Dowell E.et al Lactobacillus rhamnosus GG bacteraemia associated with probiotic use in child with short gut syndrome. Pediatr Infect Dis J 200524278–280. [PubMed] [Google Scholar]
26. Rosenfeldt V, Benfeldt E, Valerius N H.et al Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis. J Pediatr 2004145612–616. [PubMed] [Google Scholar]
27. Weston S, Halbert A, Richmond P.et al Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child 200590892–897. [PMC free article] [PubMed] [Google Scholar]
28. Caicedo R. Probiotic: protecting the intestinal ecosystem? J Pediatr 2005147143–146. [PubMed] [Google Scholar]
29. Murch S H. Probiotics as mainstream allergy therapy? Arch Dis Child 200590881–882. [PMC free article] [PubMed] [Google Scholar]
30. Hollander D, Vadheim C, Brettholz E.et al Increased intestinal permeability in patients with Crohn’s disease and their relatives. Ann Intern Med 1986105883–885. [PubMed] [Google Scholar]
Probiotics for the treatment of active Crohn’s disease
What is the purpose of this review?
The aim of this Cochrane Review was to investigate whether probiotics can induce remission in people with Crohn’s disease. We analyzed information from two studies to answer this question.
Key information
It is unclear whether probiotics are better than placebo. No serious adverse events occurred in any of the studies.
What was learned in this review?
Crohn’s disease is a disease that causes inflammation of the intestines and can lead to symptoms of mouth ulcers, abdominal pain, diarrhea, obstruction, fistulization (tunnels between the intestines and nearby organs), abscesses, malnutrition, low hemoglobin (blood) levels, and fatigue. There is some evidence to suggest that an imbalance of gut bacteria is the cause of the disease. Probiotics, which are live microorganisms, can affect gut bacteria and possibly reduce inflammation.
What are the main findings of this review?
We searched for randomized controlled trials (RCTs; clinical trials in which people are randomly assigned to one of two or more treatment groups) comparing probiotics to placebo. There were two RCTs, with information on 46 participants. These trials looked at adults. It is unclear whether probiotics differ from placebo in inducing remission of Crohn’s disease. It is unclear whether probiotics lead to differences in adverse events (minor and major) compared to placebo.
Terminals
This review found two studies investigating and showing no benefit of probiotics in the treatment of active Crohn’s disease. Since the studies were very small, no definitive conclusions can be drawn at this time. Probiotics were generally well tolerated; there was only one side effect that led to discontinuation of probiotic treatment, but details are not known. Based on the evidence presented in these studies, we cannot draw conclusions about the effectiveness of probiotics. Carefully designed studies with large numbers of participants are needed.
How up-to-date is this review?
This overview is current as of July 6, 2020.
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Translation notes:
Translation: Alexandrova Elvira Grigorievna. Editing: Yudina Ekaterina Viktorovna. Russian translation project coordination: Cochrane Russia – Cochrane Russia, Cochrane Geographic Group Associated to Cochrane Nordic. For questions related to this translation, please contact us at: cochranerussia@gmail. com;
Treatment of Crohn’s disease with probiotics
The causes of inflammation in the cavities of the gastrointestinal tract in Crohn’s disease are still ambiguous. However, recent studies suggest that the intestinal flora is a significant factor that stimulates inflammatory processes. This is confirmed by the fact that today antibiotics are successfully used to treat the disease, which suppress the bacterial flora of the patient. Replacing antibiotics with probiotics is an attractive alternative that is relatively safe and rivals traditional treatment in terms of effectiveness.
How to take probiotics for Crohn’s disease?
Complexes with probiotics are preparations containing live microorganisms that have a beneficial effect on the human body, normalizing the composition of the intestinal flora. They have a relatively high safety profile and, unlike antibiotics, do not have serious side effects. There are a number of things to consider before starting probiotic treatment.
- The success of the treatment depends on the location of the inflammation. For example, Crohn’s disease of the colon responds better to antibiotics, which means that this area can be said to be more susceptible to the action of probiotics.
- Crohn’s disease is best treated with probiotics in the early stages.
- One type of probiotic may be more effective depending on the specific properties of a particular strain.
- The amount of bacterial content also affects the success of the treatment.
Which probiotics to choose?
The choice of drugs for the normalization of intestinal microflora today is huge, and it is not so easy to choose the right remedy. Probiotics for Crohn’s disease should contain enough bacteria in a single dose and be resistant to the acidic environment of the stomach and intestines. Only modern probiotics meet these requirements.
fifth generation. These funds include BAK-SET forte and BAK-SET baby.