Probiotics in Ulcerative Colitis
Two studies have shown a significant decrease in lactobacilli concentration in colonic biopsies in patients with ulcerative colitis. Preventing or controlling the colitis is reported when the concentration of Lactobacillus was modulated through dietary supplementation with lactulose (prebiotic). This is a non digestible food ingredient that affects the host by selectively stimulating the growth and activity of one or more “probiotic” bacteria, such as Bifidobacterium and Lactobacillus that have health-promoting properties (104).
Ulcerative Colitis is a chronic inflammation of the rectal and colonic mucosa, with a poorly defined etiology. Its characteristics are bloody diarrhea and mucus associated with a negative stool culture for bacteria, ova, or parasites. There is also fecal stasis with bacterial overgrowth and mucosal ischemia.
The therapeutic role of probiotics is shown through two studies; in one of these, oral administration of Lactobacillus GG caused an increase in intestinal IgA immune response in patients with Crohn’s disease. In the other study, exogenous administration of L. reuteri (pure bacterial suspension or as fermented oatmeal soup) prevented acetic acid-induced colitis or methotrexate-induced colitis in rats.
These studies showed a significant decrease in lactobacilli concentration in patients with active ulcerative colitis. The results showed that L. plantarum was more effective in methotrexate-induced colitis, and Lactobacillus treatment prevented development of spontaneous colitis in IL-10 gene-deficient mice.
In an open label study with 20 patients, intolerant or allergic to 5-aminosalicylic acid (5-ASA), a’ treatment consisting of VSL3 6 g (1800 billions bacteria)/day for 12 months was instituted. Clinical, endoscopic assessment and stool culture and fecal pH determination were recorded (105). Nineteen patients completed the trial and 15 were in remission for the whole year. Fecal concentrations of bifidobacteria, lactobacilli, and S. salivarius spp. Thermophilus were significantly increased in all patients and remained stable throughout the study. No changes were noted in the concentrations of total aerobic bacteria, suggesting that the beneficial effects of VSL3 were not related to suppression of endogenous luminal flora. The treatment was welltolerated with no reported significant side effects like those seen in the treatment with 5-ASA oral compounds.
This shows that the probiotic preparation was able to colonize the intestine and suggested its possible usefulness in maintaining remission in ulcerative colitis patients intolerant or allergic to 5ASA (105). The hypothesis from these studies is that the intestinal environment may contribute to the pathophysiology of ulcerative colitis.
Guslandi et al. (106) studied the efficacy of S. boulardii in ulcerative colitis patients. Twenty-five patients with a mild to moderate clinical flareup of ulcerative colitis received additional treatment with S. boulardii 250 mg three times a day for 4 weeks during maintenance treatment with mesalazine. These patients were unsuitable for steroid therapy. Rachmilewitz’s clinical activity index was calculated before and after the treatment. Of the 24 patients who completed the study, 17 attained clinical remission; this was endoscopically confirmed. The preliminary results suggested that S. boulardii may be effective in the treatment of ulcerative colitis.
Probiotics in Inflammatory Bowel Disease
The term Chronic Inflammatory Bowel Disease (IBD) includes three disease types: Ulcerative Colitis, Crohn’s disease, and an intermediate form (about 10%.)
Crohn’s disease is defined as a chronic granulomatous inflammation of the digestive tract that most commonly involves the distal ileum, colon and anus. Less often, the disease affects the mouth, esophagus, stomach and duodenum. Occasionally, extraintestinal sites are affected and it is referred to as: “metastatic Crohn’s disease”.
In Ulcerative Colitis (UC), the colon is affected and the disease usually starts in the rectum and progresses proximally, although sometimes the first manifestation may be the involvement of the whole colon and rectum (panproctocolitis).
Both Crohn’s disease and Ulcerative Colitis are more common in whites that in blacks. Both sexes are equally affected. The incidence is three- to sixfold higher in Jews compared to non-Jews.
Ulcerative Colitis is slightly more common than Crohn’s disease. In Western Europe and North of America, there are 3000-5000 new cases of Crohn’s disease and 8000-10000 new cases of Ulcerative Colitis. The incidence and prevalence of Crohn’s disease have been increasing five times faster than that of Ulcerative Colitis. Young people are more likely to be more affected by inflammatory bowel disease than older people, with a peak incidence at the age of 15-30 years.
The etiology of this disease is unknown. An infectious hypothesis has been considered for years, and Mycobacterium paratuberculosis has been mainly isolated from patients with Crohn’s disease. However, some patients with ulcerative colitis harbor this pathogen. Viruses have also been involved in the pathogenesis. Several factors other than infectious agents have been postulated as the cause of the disease.
These different factors are:
- genetic and
The chronic inflammatory nature of these diseases may indicate the presence of an infectious cause or the presence of a dysregulatory abnormality in the control of inflammation.
An increasing number of both clinical and laboratory observations support the importance of the ubiquitous luminal bacteria in the inflammatory responses of these disorders (103). Bacteria are present throughout the gastrointestinal tract but are not evenly distributed and their diversity and numerical importance vary in the different sections of the gastrointestinal tract (8, 103).
In the stomach and duodenum there are facultative anaerobic bacteria (Lactobacillus spp. and Enterobacteriaceae), with a small number of bacteria that are predominantly Gram-positive and aerobic (103). In the lower distal part of the intestine there is a large variety of bacteria, mostly anaerobic bacteria belonging to Bacteroides, Bifidobacterium, Clostridium, Fusobacterium, Peptostreptococcus and Ruminococcus (8).
There is a transition to higher concentrations of bacteria and increasing number of Gram-negative bacteria in the distal ileum. Across the ileocecal valve there is a dramatic increase in bacterial concentration and more anaerobes than aerobes (103).
Enteric bacteria have been detected in patients with Crohn’s disease and in those with pouchitis. These patients may be effectively treated with antibiotics. Purified bacterial products may initiate and perpetuate experimental colitis. The inflammation is due to loss of normal tolerance to the commensal flora (103).
The onset of inflammation is associated with an imbalance in the intestinal microflora with relative predominance of “aggressive” bacteria and an insufficient concentration of “protective” species. Reconditioning the flora through either direct supplementation with protective bacteria or by indirect stimulation plays a protective role in inflammatory bowel disease (103).
Antioxidant properties, the ability to increase prostacyclin in endothelial cell cultures and the ability to modulate adhesion molecule expression on human lymphocytes are all effects which are relevant for the use of probiotics in the treatment of immunological disorders such as inflammatory bowel disease (27).