Probiotics in Intestinal Bacterial Overgrowth

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder. Pathogenesis remains multifactorial. Better understanding of the interaction of the host with intestinal microbiota the last decade led to the knowledge that many of the symptoms of IBS, mainly bloating and diarrhea, are related with the overgrowth of bacteria of colonic type in the small intestine. This overgrowth frames the syndrome of intestinal bacterial overgrowth (SIBO) where colonic type of bacteria predominate in the proximal parts of the small intestine. Fermentation of dietary carbohydrates by the bacteria colonizers of SIBO ends with the over-production of gas generating thus symptoms of IBS. The relationship between IBS and SIBO was found by a series of prospective observational studies using the lactulose and the glucose tolerance tests for the diagnosis of SIBO. Using this test, the prevalence of SIBO in patients with IBS ranged between 65 and 85%. The gold-standard technique for the diagnosis of SIBO is the quantitative culture of the content of the proximal intestine i.e. of the duodenum after upper GI tract endoscopy. Few studies are available with this design and they suggest a growth of colonic type of flora at counts equal to or greater than 10^5 cfu/ml as diagnostic of SIBO. Based on systematic review of the literature but also on data generated in a cohort of 320 consecutive patients undergoing upper GI tract endoscopy, normal subjects are never greater than 10^3 cfu/m in the duodenum. In the latter publication coming from Athens, using variable cut-offs greater than 10^3 or 10^4 or 10^5 cfu/ml for the diagnosis of SIBO, the frequency of SIBO was significantly greater among sufferers than among non-sufferers from IBS.

Oral supplementation with probiotics may be a rational approach for the eradication of SIBO and subsequently of the symptoms of IBS. The majority of probiotic bacteria belong to the Lactobacillus and Bifidobacterium genera. They are Gram-positive lactic acid-producing bacteria that constitute a major part of the normal intestinal microflora in animals and humans. The rationale behind their use as a therapeutic strategy in IBS is that orally administered probiotics may replace the overgrown enteric-type bacteria of SIBO. Four randomized clinical trials are available evaluating the efficacy of orally administered probiotics in IBS. The common findings of these trials are that a) efficacy refers to the improvement of symptoms of bloating and of diarrhea that are typical symptoms of the presence of SIBO; and b) efficacy is usually found when mixtures of different species of probiotics are used. However, no study has ever tested the efficacy of probiotics in patients with IBS and SIBO proven by small intestinal culture.

The aim of the present study is to demonstrate the effect of a mixture of four species of probiotics (Saccharomyces boulardii, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5 and Lactobacillus plantarum) in patients with symptomatic IBS who have culture verified SIBO and those who do not have. This will provide direct evidence for the role of probiotics in treating part of the pathogenesis of IBS.

Inclusion criteria

• Age ≥18 years
• Both genders
• Written informed consent by study participants
• Presence of IBS according to Rome III criteria
• Equal number of SIBO-positive and SIBO-negative patients

Exclusion criteria

• Age <18 years
• Deny to consent
• Pregnancy or lactation
• Presence of inflammatory bowel disease
• Presence of acute GI tract infection
• Diabetes mellitus type 1 or type 2
• Use of laxatives and antibiotics within the preceding 6 weeks
• Presence of fever, abdominal mass, signs of bowel obstruction and/or leucocytosis
• Abnormal serum levels of thyroid -stimulating hormone.
• History of colon cancer or diverticulitis
• Infection by human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus
• Patients with celiac disease defined by biopsy of the duodenal mucosa.
• History of scleroderma and gastroparesis
• Pregnancy or planning pregnancy the next 3 months