PROBIOTICS, PREBIOTICS, AND NEW FOODS

Probiotics in The Treatment of Irritable Bowel SyndromeAlfredo Saggioro, MD

Abstract: Irritable Bowel Syndrome (IBS) may be diagnosed on thepresence of symptoms, according to Rome II criteria and some studieshave shown that abnormal colonic fermentation may be an importantfactor in the development of symptoms in some patients with IBS.Since the fermentations of substrates by the intestinal flora may playa key role in the use of probiotics in the treatment of IBS, fifty patients(24 males,26 females), mean age 40 years (range = 26–64 years) withIBS, according to Rome II criteria, were enrolled into the study afterinformed consensus. Patients were randomly assigned to receive ei-ther the active preparation containing Lactobacillus Plantarum LP0 1and Bifidocterium Breve BR0 both at a concentration of 5 × 109

CFU/ml, or placebo powder containing starch identical to the studyproduct, for 4 weeks. To evaluate treatment efficacy two differentscores were considered: Pain score in different abdominal locationsafter treatment decreased in probiotics group of 38% versus 18% (P <0.05) of placebo group after 14 days and of 52% versus 11% (P <0.001) after 28 days. The severity score of characteristic IBD symp-toms significantly decreased in probiotic group versus placebo groupafter 14 days 49.6% versus 9.9% (P < 0.001) and these data wereconfirmed after 28 days (44.4% versus 8.5%, P < 0.001). In conclu-sion, short-term therapy with Lactobacillus PlantarumLP0 1 and Bi-fidocterium Breve BR0 may be considered a promising approach tothe therapy for IBS.

Key Words: IBS, probiotics, therapy

(J Clin Gastroenterol 2004;38:S104–S106)

Some studies have shown that abnormal colonic fermenta-tion may be an important factor in the development of

symptoms in some patients with IBS.2 In man,the large gutreceives material from the ileum which has already been di-gested and the contents are then mixed and retained for 6–12hours in the cecum and right colon.3 Thus, the large intestine isan open system, with nutrients flowing in the cecum, and bac-teria, their metabolic products, and undigested foodstuffs be-ing excreted as faeces. The anaerobic brakdown of carbohy-drate and protein by bacteria is known conventionally as fer-

mentation. In man the major end products are the schort chainfatty acids (SCFA) acetate, propionate, butirate, the gases H2and CO2, ammonia, amines, phenols and energy, which thebacteria use for growth and the maintenance of cellular func-tion.

Fermentation is active in right colon with high bacterialgrowth rates and a totalSCFA production of 127 mmol/l atpH = 5.4–5.9; in transverse colon there is a reduction in bac-terial activity due to depletion of substrates and a total SCFAproduction = 117 mmol/l at pH = 6.2; in the left colon the car-bohydrate fermentation is little, with a high fermentation ofprotein with production of phenols, indoles, ammonia.4

The fermentations of substrates by the intestinal floramay play a key role in the use of probiotics in the treatment ofIBS. Probiotics are live bacteria food supplements that benefitthe host animal by improving the intestinal microbial balance.Recents studies emphasize the role of probiotics in regulatingthe motility of the digestive tract.9 In an open study Lactoba-cillus plantarum DSM9843 has been received by patients suf-fering for IBS during 4 weeks with reduction of flatulence andabdominal pain.The probiotic has been recovered in faeces andrectal biopsies respectively in 84% and 34% of treated sub-jects.5

To assess the efficacy of Lactobacillus plantarum 299Vin IBS, 40 patients were randomized to receive either the pro-biotic in liquid suspension (20 patients) or placebo (20 pa-tients) over a period of 4 weeks. Clinical examination was per-formed at baseline and at the end of the study. Additionally,patients assessed their symptoms by applying a scoring sys-tem. All patients treated with the probiotic reported resolutionof their abdominal pain as compared with 11 patients from theplacebo group. There was also a trend toward normalization ofstools frequency in constipated patients in 6 out of 10 patientstreated with probiotic versus 2 out of 11 in the placebo group.With regards to all IBS symptoms an improvement was notedin 95% of patients in probiotic group versus 15% in the placebogroup.6

VSL#3, a composite product containing multiple strainsof 3 viable lyophilized bacteria species (Lactobacilli, Bifido-bacteria, Streptococcus), has been tested in 42 patients withIBS with advantage on pain in 81% of cases and a decrease ofstool frequency from 7.2 ± 2 to .1 ± 1.1 (P < 0.002)7; in an othertrial recently published VSL#3 appears to be promising in therelief of abdominal bloating in patients with diarrhea predomi-nant IBS.8 A recent editorial suggests the importance to plan

Received for publication January 14, 2004; accepted February 12, 2004.From Digestive Diseases, Hepatology and Clinical Nutrition Department,

Umberto I Hospital, Venice, Italy.Reprints: Alfredo Saggioro, MD, Digestive Diseases, Hepatology and Clinical

Nutrition Department, Umberto I Hospital, 30174 Venice, Italy (e-mail:asaggioro@hotmail.com).

Copyright © 2004 by Lippincott Williams & Wilkins

S104 J Clin Gastroenterol • Volume 38, Supp. 2, July 2004

randomized trials with an adeguate number of patients ran-domly allocated to probiotics or placebo to define the possibil-ity to use probiotics in the treatment of IBS.9

We undertook a placebo-controlled study to define theefficacy of a 2 composite product containing the first one strainof Lactobacillus plantarum LP01 plus one strain of Bifidocte-rium breve BR0, the second a strain of Lactobacillus planta-rum LP01 plus a strain of Lactobacillus acidophilus LA02 ver-sus placebo in the treatment of IBS.

PATIENTS, MATERIAL AND METHODS.Seventy patients (31 males, 39 females), mean age 40

years (range = 26–64 years) with IBS were enrolled in to thestudy after informed consensus. All patients had a previoushistory of IBS according to Rome II criteria1 and with an exclu-sion of organic diseas on the basis of abdominal ultrasound andcolonoscopy, treated with different drugs, without success.

Patients were randomly assigned to receive twice a dayfor 4 weeks:

TABLE 1. Pain Score at Different Locations in the RLQ and LLQ of the Abdomen

PainLocation

Day 0 Day 14 Day 28

A (24) B (26) Pl (20) A (21) B (23) Pl (18) A (21) B (23) Pl (16)

RLQ score 42 41 43 31 25 40 19 24 35% < 27 40 7 55 42 19LLQ score 61 64 66 31 25 40 19 24 35% < 27 40 7 55 42 19Epigastrium score 41 40 37 25 22 34 18 20 33% < 40 45 9 57 50 11Back score 32 34 32 13 15 18 17 18 20% < 60 56 44 47 48 38Other sites score 21 20 22 13 14 18 17 16 20% < 39 30 10 19 20 0Overall score 197 199 200 113 101 150 90 102 143% < 42 49 25 45 49 29.5

TABLE 2. Overall Symptom Score

Symptoms

Day 0 Day 14 (−%) Day 28 (−%)

A (24) B (26) Pl (20) A (21) B (23) Pl (18) A (21) B (23) Pl (16)

Constipation score 17 18 23 15 16 20 14 15 19% < 12 11.2 13 17.7 16.7 17Diarrhoea score 54 55 58 25 28 54 18 21 51% < 54 50 7 67 62 13Bloating score 47 40 44 21 23 44 15 20 41% < 55 42.5 2.3 68 50 7Flatulence score 51 46 45 19 20 39 16 18 36% < 37.2 57 20 69 60.1 20Nausea score 19 18 21 16 17 19 12 14 18% < 16 6 10 17 23 15Cephalea score 27 26 26 14 18 24 14 17 18% < 49 31 8 49 35 31Dyspepsia score 38 34 33 21 27 30 22 24 31% < 45 21 10 43 30 7Overall score 253 237 250 131 149 230 111 129 214% < 49.3 55.6 8 56 55.6 14.4

J Clin Gastroenterol • Volume 38, Supp. 2, July 2004 Probiotics in IBS

© 2004 Lippincott Williams & Wilkins S105

Group A: Lactobacillus plantarum LP01 (Probial) + Bifidoc-terium breve BR0 (Probial) 5 × 109 CFU/ml each in apowder form soluble in water once a day

Group B: Lactobacillus plantarum LP0 1 (Probial) + Lacto-bacillus acidophilus LA0 2 (Probial), 5 × 109

CFU/ml each in a powder form soluble in water once a dayGroup C: placebo powdwer containing starch identical to the

study product, for 4 weeks. A complete clinical exami-nation was performed at baseline and at the end of thestudy. To evaluate traetment efficacy two differentscores have been considered:

1. Severity of abdominal pain at different locations: rightlower quadrant (RLQ), left lower quadrant (LLR),epigas-trium,back,other locations. Score: 0 = no pain, 1, 2, 3 = low,medium, high severity

2. Severitiy of IBS symptoms (constipation, diarrhea, bloat-ing, flatulence, cephalea, nausea, dyspepsia). Score: 0 = nosymptoms; 1, 2, 3 = low, medium, high

RESULTSSeventy patients have been considered valuable on the

basis of “intention to treat”: 24 in Group A, 26 in Group B, 20in Placebo Group.

The ovarall “pain socre” (Table 1) in Group A decreasedby 42% and 45%, respectively, at day 14 and at day 28; inGroup B by 49% both at days 14 and 28; in placebo Group by25% and 29.5%. The best results were achieved for pain inRLQ and LLQ.

The overall symptoms score (Table 2) in Group A de-creased by 49.3% and 56%, respectively, at day 14 and at day28; in Group B by 55.6%, both at days 14 and 28; in placeboGroup by 8% and 14.4%.

No statistical evaluation is possible due to the smallnumber of patients studied, but a clear advantage for probiotictreated group versus placebo is evident.

In conclusion the preparations containing Lactobacillusplantarum LP01 (Probial) + Bifidocterium breve BR0 (Pro-bial) and Lactobacillus plantarum LP0 (Probial)1 + Lactoba-cillus acidophilus LA0 (Probial) 2, may both be considered aninterestin tool in the terapy of IBS. Further studies are neededto confirm these preliminary data.

REFERENCES.

1. Drossmann A, Corazziari E, Talley NL, et al. Rome II: the functionalgastrointesdtinal disorders: diagnosis,pathophysiology and treatment: amultinational consensus. 2nd ed. McLean,VA: Degnon Associates; 2000

2. King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritablebowel sindrome. Lancet. 1998;352:1187–1189.

3. Cummings JH, Macfarlane GT. The control and consequences of bacterialfermentation in the human colon. J Appl Bacteriol. 1991;70:443–459.

4. Cummings JH, Englyst HN. Fermentation in the human large intestineand the available substrates. Amer J Clin Nutr. 1987;45:1243–1255.

5. Nobaek S, Johanssen ML, Molin G, et al. Alteration of intestinal micro-flora is associated with reduction of abdominal bloating and pain in pa-tients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231–1238.

6. Niedzielin K, Kordecki H, Birkenfeld B. A controlled double-blind ran-domized study on the efficacy of Lactobacillus plantarum 299V in pa-tients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2001;13:1143–1147.

7. Bazzocchi G, Gionchetti P, Almerigi PF, et al. Intestinal microflora andoral bacteriotherapy in irritable bowel syndrome. Dig Liver Dis.2002;34(suppl 1):S48–S53.

8. Kim HJ, Camilleri M, McKinzie S, et al. A randomized controlled trial ofa probiotic,VSL#3, on gut transit and symptoms in diarrhoea predominantirritable bowel syndrome. Alimet Pharmacol Ther. 2003;17:895–904.

9. Thompson WG. Probiotics for irritable bowel syndrome: a light in thedarkness? Europ J Gastroenterol Hepatol. 2001;13:1135–1136.

Saggioro J Clin Gastroenterol • Volume 38, Supp. 2, July 2004

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