Bacteria are present throughout the gastrointestinal tract, but the pattern and concentration vary greatly. The stomach normally contains a relatively small number of bacteria that are predominantly gram positive and aerobic. In the proximal small intestine, bacterial concentration and pattern are quite similar of those of the stomach. However, along the length of the small intestine, there is a transition to higher concentrations of bacteria and an increasing predominance of gram negative species in the distal ileum. A dramatic increase in bacterial concentration is present across the ileal-caecal valve with the total number of microorganisms increasing by approximately a million fold (from 108 to 1010 - 1011) and anaerobes outnumbering aerobes by a ratio of 1000:1.

While inflammatory processes per se have been extensively studied, relatively little attention has been directed to the important role of luminal bacteria in inflammatory bowel disease (IBD) pathogenesis. However, an increasing number of both clinical and laboratory-derived observations support the importance of constituents within a lumen in driving the inflammatory responses in these disorders. For example, it has long been recognized that the anatomic sites of highest bacterial concentration (distal ileum and colon) are the sites most frequently affected by inflammation in patients with IBD.

The clinical importance of these bacteria is supported by many observations. Entire bacteria or their products have been detected within inflamed mucosa of patients with Crohn’s disease. Similarly, pouchitis, the non-specific inflammation frequently present in the ileal reservoir after illeoanal anastomosis, appears to be associated with concentrations of bacteria. Clinical experience has suggested that activity in patients with Crohn’s disease can be reduced through the use of antibiotics or diversion of the faecal stream, supporting the general notion of the importance of bacteria in sustaining inflammation in IBD. Patients with pouchitis may also be effectively treated with antibiotics. Additionally, recent studies have shown directly the ability of luminal contents presumably dominated by bacteria or their products to trigger postoperative recurrence in the terminal ileum within a few days, providing further evidence of the role of luminal contents. Purified bacterial products can initiate and perpetuate experimental colitis. In some experimental models, perpetuation of inflammation has been suggested to derive from loss of normal tolerance to the commensal flora. Finally, it has been noted that the spontaneous colitis that consistently develops in many transgenic and knockout mutant murine models of colitis may not occur when these lines are maintained in germfree conditions.

Most probiotics belong to a large group of bacteria empirically designated as lactic acid bacteria (labctobacilli, streptococci, bifidobacteria) that are important components of the human gastrointestinal microflora where they exist as harmless commensals. Lactic acid is the principal end product of metabolism for all these species. New probiotics also include other microbes such as yeast (e.g. Saccharomyces boulardii) and entirely unrelated bacteria (clostridium, Bacillus subtilis). Probiotic strains must be of human origin because some health-promoting effects may be species specific. They also must be both acid and bile resistant and have the ability to sustain metabolic activity within the luminal flora, where ideally they should survive, if not persist, for the long term. These strains are presumed to be antagonistic against pathogenic bacteria through the production of anti-microbial substances and promoting a reduced luminal colonic pH. It is axiomatic that they must be safe for human use and should maintain their viability and other beneficial products through processing, culture, and storage.

Substances that serve as prebiotics to affect alteration in luminal bacteria must be neither hydrolyzed nor absorbed in the upper part of the gastrointestinal tract, and they have to represent a selective substrate for a limited number of beneficial bacteria. Nondigestible carbohydrates are considered the best candidate prebiotics. Lactulose was shown to increase concentration of Bifidobacterium bifidus in bottle-fed infants and to stimulate growth of lactobacilli in the colon to reduce ammonium absorption in hepatic encephalopathy.

A pilot study using Probiotic preparation as maintenance treatment in patients allergic or intolerant to sulphasalazine or mesalamine was carried out. Twenty patients received 6/g of probiotic preparation daily for 12 months and were periodically assessed; stool culture and determination of faecal pH were also performed at various intervals. Microbiological determination showed a significant increase in concentrations of lactobacilli, bifidobacteria and S.salivarius subsp. thermophilus, which was evident after 10 days and persisted through the treatment period. No significant modification was seen in the concentrations of the other bacterial species. Faecal pH was significantly reduced by the treatment, and most patients (75%) remained in remission.

Subsequently, efficacy of this oral probiotic preparation was compared with placebo in the maintenance treatment of chronic relapsing pouchitis. Forty patients who obtained clinical and endoscopic remission after 1 month of antibiotic treatment (rifaximin, 1 g twice daily, plus ciprofloxacin, 500 mg twice daily) were randomized to receive 6 g of probiotic preparation daily or an identical-appearing placebo for 9 months. Of the 20 patients who received the placebo, all had a relapse, 8 within 2 months, 7 within 3 months, and the remaining 5 within 4 months. In contrast, 17 of the 20 patients treated with probiotic preparation were still in remission after 9 months. All of these 17 patients had a relapse within 4 months after suspension of the treatment. Faecal concentrations of lactobacilli, bifidobacteria, and S. salivarius subsp. thermophilus were significantly increased within 1 month of initializing probiotic preparation treatment and remained stable throughout the study.

Can we thus, conclude that the use of Probiotics and prebiotics is an effective approach for patients with IBD and say BUGS ARE BETTER THAN DRUGS?

Consultant Hepatogastroenterologist, Bombay Hospital Institute of Medical Sciences, Formerly Associate Professor of Medicine and Gastroenterology, Grant Medical College and Sir JJ Group of Hospitals, Mumbai.