Volume 10 - Issue 1, October 2017

Therapeutic potential of Bifidobacterium infantis 35624™ (Bifantis®) in irritable bowel syndrome Back

IBS and dysbiosis

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterised by abdominal pain or discomfort, and alterations in bowel habit 1,2. It is often associated with other symptoms such as gas, bloating, and urgency. IBS is one of the most common disorders managed by physicians, and can result in significant reductions in quality of life for patients. The condition affects 10% to 15% of the population in Europe and North America, and its prevalence is increasing in countries in the Asia-pacific region.3 In Australia, approximately one in five individuals experiences the unpleasant symptoms of IBS at some time.4

Gut dysmotility and altered visceral sensation, along with psychosocial factors, are traditionally thought to be involved in the pathophysiology of IBS. More recently, other factors have also been implicated, including abnormal gut-brain interaction, enteric infections, intestinal mucosal inflammation, and abnormalities in the enteric flora.5-7

In particular, there is evidence for the presence of dysbiosis in IBS. Levels of several species of commensal bacteria have been found to be disturbed in patients with IBS, including Bifidobacterium spp, Lactobacillus spp, and Veillonella spp, as well as other bacterial groups.8 In addition, the observation that antibiotics can exacerbate IBS contributes to the paradigm that IBS may be influenced by the gut flora.9 There is thus a strong rationale for targeting the gut microbiota in an effort to relieve IBS symptoms.

Potential role of probiotics in IBS

Probiotics are live microorganisms that provide health benefits when administered in sufficient quantities.10,11 The properties of  various microorganisms appear to be largely strain-specific, and different strains may show different therapeutic potential in a particular condition.10-12 In addition, different strains of probiotics have been shown to be effective at different levels. There is no minimum or maximum number of bacteria that must be ingested to obtain a beneficial effect. The required amount/dose varies for different probiotic strains and the specific health effect. While theoretically appealing, a probiotic with multiple strains is not necessarily better than a probiotic with a single strain. For multiple strain probiotics it is important to look at the compatibility of the strains to be sure the combination of strains has a synergistic, rather than antagonistic effect.12,13

Recent meta-analyses and systematic reviews indicate a strong potential role for probiotics in IBS treatment. 14,15 Bifidobacteria and lactobacilli are subjects of considerable interest. A range of strains, formulations, doses, and delivery methods have been studied in patients with IBS, with varying clinical outcomes. Several specific strains or products, including Bifidobacterium infantis 35624™ (Bifantis®), Bifidobacterium lactis DN-173010, Bifidobacterium bifidum MIMBb75, and the probiotic cocktail, VSL#3®, have demonstrated efficacy in reducing various cardinal symptoms of IBS in clinical trials.16,17 

Bifidobacterium infantis 35624 (Bifantis®) is of particular interest, backed by evidence from randomised,  doubleblind, placebo-controlled trials.18, 19 This strain has recently become commercially available in Australia under the brand name Meta Align®.

Bifidobacterium infantis 35624™: Clinical efficacy in IBS

Bifidobacterium infantis 35624 has been shown to improve both global/composite symptom scores and specific individual cardinal symptoms in two well-controlled trials in patients with IBS (Table 1).18,19 These benefits may be partially attributable to the ability of Bifidobacterium infantis 35624 to induce immunomodulatory effects.20, 21

Relief of IBS symptoms

A randomised, double-blind placebo-controlled study was undertaken by O’Mahony et al (2005)19 in 75 evaluable men and women with IBS. The study included all IBS subtypes; 45% were alternators, 28% were diarrhoea predominant, and 26% were constipation predominant according to Rome II criteria. The results demonstrated significant symptomatic improvement with Bifidobacterium infantis 35624 compared with placebo, including improvement in functional abdominal pain/ discomfort, bloating/ distension, bowel movement difficulty and composite symptom scores during most weeks of the 8-week treatment period. Composite symptom scores were also significantly improved with Bifidobacterium infantis 35624 versus a Lactobacillus strain (L salivarius UCC4331), during most weeks. In contrast, patients receiving the Lactobacillus strain showed composite symptom score improvement versus placebo only during the second week of treatment.

While the O’Mahony trial delivered probiotics in a malted milk drink, a confirmatory study by Whorwell et al (2006)18 evaluated Bifidobacterium
infantis 35624 as an encapsulated encapsulated formulation. 362 female patients with different IBS sub-types (55% diarrhoea-predominant, 21% constipation-predominant, and 24% alternators) were randomised to receive Bifidobacterium infantis 35624 at a concentration of 1×106 live bacterial cells (n = 90), 1×108 cells (n = 90), or 1×1010 cells (n = 90), or matching placebo (n = 92), administered daily for four weeks followed by a two-week washout.

Table 1

  • Abdominal pain/discomfort
  • Bloating/distension
  • Bowel movement difficulty
  • Passage of gas
  • Sense of incomplete evacuation
  • Straining
  • Composite symptom scores
  • Global assessments of IBS symptoms relief

Table 1. IBS symptoms improved in patients receiving daily administration
of Bifidobacterium infantis 35624 (versus placebo) 18,19

Among patients receiving the Bifidobacterium infantis 35624 probiotic, those receiving the 1×108 dose appeared to derive the greatest benefit. After four weeks of treatment, abdominal pain and discomfort were significantly improved versus placebo (p=0.023 ) (Figure 1). The 1×108 dose also significantly improved other symptoms compared with placebo, including bloating/distension, passage of gas, sense of incomplete evacuation, straining, and bowel habit satisfaction, as well as global assessments of IBS symptoms relief” and a composite symptom score. Symptomatic improvements were gradually lost during the washout period, suggesting that continued daily dosing may be necessary for ongoing effect.18
.18

Notably, in this study the observed improvement in subjects’ global assessment (SGA) was in excess of 20% over placebo (Figure 2), which was greater than the effects on individual symptoms – suggesting that other non-classical elements of symptomatology that are important to patient satisfaction, but are not routinely assessed in clinical studies, may be improved with the use of Bifidobacterium infantis 35624.18

Bifidobacterium infantis 35624: Safety data

Probiotics are generally considered to be well tolerated; and the available literature indicates that Bifidobacterium infantis 35624 is well tolerated in IBS patients.18, 19, 22, 23 In the Whorwell et al study, fewer than 5% of patients overall withdrew from the study due to adverse events (AEs), and Bifidobacterium-treated patients showed a similar rate of AEs compared with those receiving placebo.18 In the O’Mahony trial, only four patients experienced AEs across all three cohorts (Bifidobacterium infantis 35624, Lactobacillus spp, and placebo combined).19 Notably, the European Society for Primary Care Gastroenterology consensus paper (2013) showed 100% agreement and high evidence levels supporting the favourable safety of probiotics such as Bifidobacterium infantis 35624 in primary care.23

Evidence for anti-inflammatory/ immunomodulatory activity
The mechanism of action of probiotics is an emerging science. Scientific research
suggests that possible mechanisms of action of probiotics include rebalancing the intestinal bacteria, modulating cytokine profiles, and stimulating non-immune mechanisms such as release of acid, competition for attachment sites, and digestion of food and nutrients.24 However, mechanisms may vary from one probiotic to another, and may entail a combination of events, making this a very difficult and complex area of research.

Although, the mechanism of action of Bifidobacterium infantis 35624 is not fully understood, current research suggests that there is an up-regulation of anti-inflammatory cytokines (interleukin [IL]-10) with little impact, or a down-regulation of pro-inflammatory cytokines (IL-12, IL-1β, interferon [IFN]-γ, tumor necrosis actor [TNF]-α). Thus, Bifidobacterium infantis 35624 helps to promote the balance of cytokine mediators resulting in a healthy inflammation response.20, 21

Probiotic Effectiveness Ranking

A 2015 consensus opinion paper from the 4th Triennial Yale/Harvard Workshop on Probiotics recommends Bifidobacterium infantis 35624 for IBS as Category B† for
effectiveness.25
Further, an international consensus paper from the European Society for Primary Care Gastroenterology (2013)23 showed 100% consensus (high or moderate grade of evidence for effect) that probiotics such as Bifidobacterium infantis 35624 help relieve overall IBS symptom burden and abdominal pain in some patients with IBS. There was moderate evidence with 70% agreement supporting the effectiveness of such probiotics in reducing bloating/distension symptoms and bowel movement frequency/consistency.23 †Category B effectiveness: Positive controlled studies with presence of some negative studies not supporting primary outcome.

Probiotic Guidelines for IBS

The World Gastroenterology Organisation (WGO) Global Guidelines on Irritable Bowel Syndrome (September 2015) suggest that, along with dietary and lifestyle review, a quality probiotic with proven efficacy can be trialled when available.3 Further, these guidelines state that Bifidobacterium infantis 35624 currently has “the best evidence base for efficacy in IBS”.3

Updated WGO guidelines (2017) rank the evidence for Bifidobacterium infantis 35624 effectiveness at level 2 (randomised trial or observational study with dramatic effect), and reiterate the reductions in bloating and flatulence with probiotic treatment, including those achieved with Bifidobacterium infantis 35624, are “a consistent finding in clinical studies.”24.

Toward the future

Taken together, the data suggest a role for some probiotics in the symptomatic treatment
of IBS, perhaps as a supplement to standard therapy. With evidence from  randomised trials, Bifidobacterium infantis 35624, in particular, appears to show benefit for a range of cardinal IBS symptoms, including gas, bloating and abdominal pain.18, 19 This generalised beneficial effect on symptoms in patients with all IBS subtypes is clinically significant, given that some traditional or standard IIBS treatment focus only on a specific IBS-subtype and/or improvement of a single symptom.18

Take-home messages

  • There is evidence for the presence of dysbiosis in IBS, providing strong rationale for the use of probiotics for symptom control. While the literature strongly suggests a potential role for some probiotics, there is a need for further large,well-designed, long-term studies of specific organisms.
  • Bifidobacterium infantis 35624 is currently of particular interest, and its potential in IBS symptom control is supported by evidence from randomised, controlled trials. WGO guidelines state that this probiotic has “the best evidence base for efficacy in IBS”.3
  • Bifidobacterium infantis 35624 has been shown to significantly improve cardinal symptoms of medically diagnosed IBS, including abdominal pain, gas and bloating, as well as composite symptom scores, compared with placebo. These effects are apparent regardless of predominant IBS subtype.18, 19
  • It is thought that the improvement in symptoms may be in part due to the ability of Bifidobacterium infantis 35624 to help to promote a more normal balance of cytokine mediators, resulting in a healthy inflammation response within the host gut.25, 26

References

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  20. Konieczna P, et al. Bifidobacterium infantis 35624 administration induces Foxp3 T Regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut. 2012 Mar;61(3):354-66.
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    processes beyond the gut. Gut Microbes. 2013 July/August;4(4):325-339.
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