THE EFFECT OF A NEW PROBIOTIC PRODUCT LINE IN PATIENTS WITH IRRITABLE BOWEL

VentsislavNakov and RadislavNakov. Clinic of Gastroenterology; “TsaritsaYoanna –ISUL“ University Hospital, Medical University of Sofia, Bulgaria. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


Background
It has been proven for many years that probiotics play pivotal role in the treatment of IBS patients. However it is still not very clear which strains are more beneficial than others in the treatment of irritable bowel syndrome (IBS).Our aim in the current clinical observation was to follow up the effect of a novel probiotic product line available on the Bulgarian market -Biopron IB-Symbio (Walmark, Czech Republic) in the treatment of IBS patients.

Methods
This prospective clinical observation included 45 consecutive patients divided into three groups: group 1 -15 patients with diarrhea predominant post-infectious IBS (IBS-D), group 2 -15 with constipation-predominant IBS (IBS-C) and group 3 -15 IBS patients meeting Rome III but not meeting Rome IV criteria. Four week monotherapy with a new probiotic line was commenced in every group. The symptoms were evaluated before and after treatment. Moreover in IBS-D group fecal calprotectin (FCP) was monitored Results Significant reduction of FCP mean levels was observed in group 1from 152 µg/g at week 0 to 64 µg/gat week 4 (p<0,001). After probiotic treatment diarrhea was present only in 3 (20%) patients, and pain in 5 (33%) of the patients. In group 2 constipation was present after treatment just in 2 (13%) patients and abdominal pain in 4 (27%) of them. In group 3 -at 4 week after treatment discomfort was present in 3 (20%) patients, bloating in 2 (13%) patients and change in frequency of stool in 4 (27%)

Conclusion
The current clinical observation shows that Biopron probiotic product line significantly improves the symptoms in IBS patients. Moreover, it reduces the inflammatory activity in patients with post-infectious IBS.Additional multicenter observations with larger number of patients from different regions are needed to obtain even more accurate data Irritable bowel syndrome (IBS) is a common functional condition of unclear, complex pathophysiology that has a large impact on quality of life and both direct and indirect healthcare costs (1,2). It is the most frequent diagnosed gastrointestinal disorder and one of the most common functional disorders of the gastrointestinal tract (GIT) in the clinical practice (41% from all patients with GIT disorders). The prevalence of IBS in the developed countries is between 5% and 20%. (3).
IBS demonstrates variable clinical course with a broad spectrum of gastrointestinal and extraintestinal symptoms. It is a chronic disease but with a good prognosis and does not lead to increased mortality compared to general population (4).
Recently, there are growing evidences about the role of acute gastrointestinal infections in the development of IBSpost-infectious IBS. It is observed in 10-30% of the patients following acute episode of infectious gastroenteritis. The percentage in Bulgaria is even higher -44% of patients with post-infectious enteritis (5). The underlying causes consist of a variety of chronic and persistent clinical manifestations of the intestinal inflammation after acute infection; morphological lesions and disintegration of the intestinal mucosa; impairment of barrier function with increased intestinal permeability and excessive lumen exposure to antigens; the entry of these antigens into the lining and activation of the local immune, endocrine and autoimmune system; secretion of proinflammatory factors, gastrointestinal hormones, physiologically active substances, etc. (5).
In 2016 the "Rome foundation" accepted the new criteria for IBS diagnostics -Rome IV (  (6))(Table 2) is that the symptom discomfort is eliminated, and it is already assumed that a patient has IBS only if recurrent abdominal pain is present at least once in a week instead of at least three times per month.
A potential problem arises from this last revision due to the existence of a group of patients that demonstrate symptoms correlating to the Rome III criteria but still do not fulfill the Rome IV criteria. (7).   Recurrent abdominal pain or discomfort † more than 3 days per month over the previous 3 months associated with two or more of the following: 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form or appearance of stool Symptom onset greater than 6 months prior to the diagnosis, with the above criteria fulfilled for the past 3 months †Discomfort means an uncomfortable sensation not described as pain There are many pharmacological and nonpharmacological treatment options for IBS, each of which demonstrate different outcomes (8). Due to the heterogeneity of symptoms IBS should be treated individually in each patient. Of key importance is the doctor-patient communication together with proper training and recommendations about suitable diet and physical exercises.

1003
It has been proven for many years that probiotics play pivotal role in the treatment of IBS patients. However it is still not very clear which strains are more beneficial than others in the treatment of IBS (9). In the clinical practice symbiotics, containing probiotics together with prebiotics are commonly prescribed.
Our aim in the current clinical observation was to follow up the effect of a novel probiotic product line available on the Bulgarian market -Biopron IB-Symbio (Walmark, Czech Republic) in the treatment of IBS patients.

Materials and methods:-
This prospective clinical observation included 45 consecutive patients who visited the Clinic of Gastroenterology at "TsaritsaYoanna -ISUL" University Hospital between December 2017 and March 2018. The patients were divided into three groups.

Results:-
All patients from group 1 (IBS-D) demonstrated diarrhea and abdominal pain before the commencement of monotherapy with Biopron S. boulardii. Four weeks later diarrhea was present only in 3 (20%) patients, and pain in 5 (33%) patients (Table 6). Significant reduction of FCP mean levels was observedfrom 152 µg/g at week 0 to 64 µg/g at week 4 (p<0,001). (Figure 1).  (Table 7). Table 7:-Presence of constipation and abdominal pain in patients with IBS-C before and after 4 week treatment with Biopron Fibers All patients in group 3 had abdominal discomfort, bloating and change in frequency of stool before treatment with Biopron Enzymes. At week 4 after treatment discomfort was still present in 3 (20%) patients, bloating in 2 (13%) patients and change in frequency of stool in 4 (27%) ( Table 8).

Discussion:-
The effect of symbiotics in IBS patients is well studied (9). Probiotics are capable of inhibiting the adhesion and the invasion of the pathogens to the epithelial wall, to eradicate microbes via production of antimicrobial products, to stimulate the cell turnover and the immune response, to induce the production of anti-inflammatory cytokins (IL10, TGF, IgA, ↓TNF) and to stimulate the phagocytic function of the neutrophils (11). Furthermore, the consumption of 1006 trans-galactooligosaccharides stimulates specific intestinal Bifidobacteria in patients with IBS and effectively alleviates the symptoms of the diseases (12,13).
The current clinical observation demonstrates that the intake of Biopron S. boulardii for 4 weeks by patients with post-infectious IBS leads to improvement of diarrhea in 80% of the patients, alleviation of abdominal pain in 67% of the patients and reduction of mean FCP levels therefore the level of intestinal inflammation.
In our previous studies we demonstrated that probiotics lead to a reduction in inflammatory activity in patients with post-infectious IBS, resulting in a reduction in FCP values and reduction or even disappearance of clinical symptoms (11). A number of other studies have also shown that the intake of symbiotics in IBS patients leads to improvement of symptoms and quality of life (9,14).
In patients with IBS-C 4-week therapy with Biopron Fibers leads to reduction of constipation in 87% of the patients and alleviation of pain in 73% of the patients. Having in mind that in clinical practice, gastroenterologists are not prescribing symbiotics very often to patients with chronic constipation, we find these results quite important. The study outcomes clearly demonstrated that the combination between psyllium and symbiotic improves the symptoms in patients with IBS-C.
The effects of psyllium in chronic constipation has been known for decades (15). A number of studies have demonstrated that psyllium has the ability to influence abdominal pain and discomfort as well as the difficulty of defecation (16). Colecchia et al. found that symbiotic containing Bifidobacteriumlongum (also present in Biopron Fibers) and short-chained oligosaccharide prebiotic leads to increase in the frequency of defecation in IBS-C patients, as well as reduction in abdominal pain and bloating (17).  (7) 40% of patients responding to Rome III did not meet Rome IV due to lack of abdominal pain, lower incidence of pain and/or lack of relationship between pain and defecation. Hence, it is quite normal to ask ourselves whether these patients have a disease or their complaints are due to other factors (e.g. diet) and if they have a disease -what is it and how to deal with its symptoms?
Following the above mentioned assumptions we followed-up 15 patients meeting Rome III criteria but not meeting Rome IV and offered them a monotherapy with Biopron Enzymes. After 4 weeks of treatment we found amelioration of abdominal discomfort in 80% of the patients, reduction of bloating in 87% and normalization of frequency of stool in 73% of the patients.
Several other studies also demonstrate a positive effect of digestive enzymes on the symptoms of IBS patients (19,20). A study among 18 healthy volunteers has shown that digestive enzyme intake along with a high-calories diet leads to significant reductions in bloating, meteorism and abdominal discomfort (19).

Conclusions:-
The current clinical observation shows that Biopron probiotic product line significantly improves the symptoms in IBS patients. Moreover, Biopron S. Boulardii reduces the inflammatory activity in patients with post-infectious IBS. Additional multicenter observations with a larger number of patients from different regions are needed to obtain even more accurate data on the effect of Biopron in patients with IBS.