ProBioticsForHealth

Probiotics are great for helping Diarrhea.

Do you know that you have literally millions of friendly bacteria that live in your gut?

What’s more, they’re essential to maintain good digestive function. Unfortunately, when you
experience diarrhea this upsets the normal balance of these friendly bacteria, also known as
probiotics. They are helpful bacteria or sometimes even healthy yeasts, and these friendly
bacteria help overcome many kinds of diarrhea.

The best understanding that we have about how beneficial probiotics can be is seen in studies
of diarrhea in kids, especially infectious diarrhea that is caused by rotavirus. The studies
show that probiotics shorten the time of kids having diarrhea by 1/2 to 2 days. The most
effective strains are Lactobacilllus reuteri and Saccharomyces boulardii. Infact Saccharomyces
Boulardii is one of the strains found in our best seller for kids, Primal Defense.

Traveling internationally is another reason for coming down with a bout of diarrhea. Very often
it’s a matter of eating contaminated food or water, or merely being a new environment where the
bacteria are unfamiliar to your body. is a frequent problem for travelers. Taking probiotics
before you travel can lower your risk of getting diarrhea. We get very good results with Dr
Ohhira’as Original Probiotics formula.

Talking about Dr Ohhira’s prrobiotic, there is clinical research to show its effectivity
against C. difficile
, which is often acquired after a hospital stay. C difficile may lead to
severe and sometimes life-threatening diarrhea and colitis. So taking these probiotics may help
prevent C. difficile infection and even more importantly that it may control repeat infections.

Other studies show that Saccharomyces boulardii and Lactobacillus GG are alos effective. In one
large study, people who were suffering with recurrent diarrhea were given a probiotic or a pill
that was not a probiotic, ie a placebo. They found that only 9 out of 26 people in the group
taking probiotics had a further recurrence of the diarrhea while in the other group who were
taking the placebo, 22 out of 34 had recurrent diarrhea.

Another probiotic that has been in the news lately, is VSL#3. This is because it has been shown
to be very effective in reducing symptoms of Ulcerative Colitis. This is a very important
finding because the drugs that are usually prescribed have many side effects with adverse
effects on the immune system.  Now the Junior Packs are also available.

Another very important time to be supplementing with probiotics is when taking antibiotics.
Unfortunately, although antibiotics kill the bad bacteria that make you sick, they also kill
the good bacteria. This leads to a dsiruption of the normal balance of the gut flora in the
gut and that may cause diarrhea. In fact, diarrhea is known to be a common side effect in as
many as 10% – 30% of those who take antibiotics. We recommend that you consider giving your
kids and even taking them yourself, before, during and most importantly after you take
antibiotics.

This will lower your risk or at least shorten the length of time you experience diarrhea.
Studies using Saccharomyces boulardii and Lactobacillus GG seem to be the most effective.
Lactobacillus GG is the probiotic used in Culturelle.

Probiotics are very safe to use for people of all ages. They rarely cause side effects, perhaps
some gas, however, that’s usually due to a type of  ‘detox’ or Herxheimer reaction when the bad
bacteria are dying off andcausing symptoms. Other important factors to take into account are
the quality and strength of the particular brand. Its very important to select effective
probiotics and also to take a high enough number of live microorganisms to make it worth while

24 Acknowledgements

Acknowledgements for Probiotics Article

O. Karimi received support from the Foundation of Immunogenetics. A.S. Pefia’s research in inflammatory bowel disease for 2002-2003 was supported in part by funding from the Crohn’s and Colitis Foundation of America (CCFA).

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  90. Gorbach, S.L., Chang, TW, Goldin, B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 1987; 2: 1519.
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  92. Prantera, C., Scribano, M.L., Falasco, G., Andreoli, A., Luzi, C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s disease: A randomised controlled trial with Lactobacillus GG. Gut 2002; 51: 405-9.
  93. Biancone, L., De Nigris, F., Del Vecchio Blanco, et al. Lactobacillus GG is not effective in subsiding bowel tenderness in inactive Crohn’s disease. Gastroenterology 2003: T1402A.
  94. Vanderhoof, J.A., Young, R.J. Role of probiotics in the management of patients with food allergy. Ann Allergy Asthma Immunol 2003; 90: 99-103.
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  97. Kalliomaki, M., Salminen, S., Poussa, T., Arvilommi, H., Isolauri, E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361: 1869-71.
  98. Ibnou-Zekri, N., Blum, S., Schiffrin, E.J., Von Der Weid, T. Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro. Infect Immun 2003, 71: 428-36.
  99. Coakley, M., Ross, R.P., Nordgren, M., Fitzgerald, G., Devery, R., Stanton, C. Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol 2003, 94: 138-45.
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23 Future Perspectives

Future Perspectives in Probiotic Use

Lactobacilli derived from the endogenous flora of normal donors are being increasingly used as probiotics in functional foods and as vaccine carriers. However, a variety of studies carried out with distinct strains of lactobacilli have suggested heterogeneous and strain-specific effects (Table IV).

To dissect this heterogeneity at the immunological level, Ibnou-Zekri et al. (137) selected two strains of lactobacilli that displayed similar properties in vitro and studied their impact on mucosal and systemic B-cell responses in monoxenic mice. Germ-free mice were colonized with L. johnsonii (NCC 533) or L. paracasei (NCC 2461). Bacterial loads were monitored for 30 days in intestinal tissues, and mucosal and systemic B-cell responses were measured.

Although both Lactobacillus strains displayed similar growth, survival, and adherence properties in vitro, they colonized the intestinal lumen and translocated into mucosal lymphoid organs at different densities. L. johnsonii colonized the intestine very efficiently at high levels, whereas the number of L. paracasei decreased rapidly and it colonized at low levels. They determined whether this difference in colonization correlated with an induction of different types of immune responses, and observed that colonization with either strain induced similar germinal center formation and IgA bearing lymphocytes in the mucosa, suggesting that both strains may activate mucosal B-cell responses.

However, clear differences in the patterns of immunoglobulins were observed between the two strains in the mucosa and in the periphery. Therefore, despite similar in vitro probiotic properties, distinct Lactobacillus strains may colonize the gut differently and generate divergent immune responses.

In another study, Coakley et al. (138), assessed strains of Lactobacillus, Lactococcus, Pediococcus and Bifidobacterium for their ability to produce the health-promoting fatty acid conjugated linoleic acid from free linoleic acid. Strains of Lactobacillus, Lactococcus, Pediococcus and Bifidobacterium were grown in medium containing free linoleic acid. Growth of the bacteria in linoleic acid and conversion of the linoleic acid to conjugated linoleic acid was assessed.

Of the bacteria assessed, nine strains of Bifidobacterium produced the cg, t11 CLA isomer from free linoleic acid. The cg, t11 conjugated linoleic acid isomer was also produced by some strains, but at much lower concentrations. Thus, the production of conjugated linoleic acid by bifidobacteria showed considerable interspecies variation.

Bifidobacterium breve and B. dentium were the most efficient producers of conjugated linoleic acid among the range of strains tested, with B. breve converting up to 65% linoleic acid to cg, t11 conjugated linoleic acid when grown in 0.55 mg/ml linoleic acid. Strains also varied considerably with respect to their sensitivity to linoleic acid. The production of conjugated linoleic acid by probiotic bifidobacteria offers a possible mechanism for some health-enhancing properties of bifidobacteria and provides novel opportunities for the development of functional foods.

Finally, it has been demonstrated that the therapeutic dose of IL-10 may be reduced by localized delivery of a probiotic genetically engineered to secrete the cytokine. Intra-gastric administration of IL10-secreting Lactococcus lactis caused a 50% reduction in colitis in mice treated with dextran sulfate sodium and prevented the onset of colitis in IL-10 gene-deficient mice (139). This observation has also opened the way for the use of probiotics as live vaccine delivery vectors (140).

22 Irritable Bowel Syndrome

Probiotics in Irritable Bowel Syndrome – IBS

Irritable Bowel Syndrome is a widespread and multi-factorial functional disorder of the digestive tract (114). It affects 8-22% of the population with a higher prevalence in women. It accounts for 20-50% of referrals to gastroenterology clinics and is char­acterized by abdominal pain, excessive flatus, vari­able bowel habit and abdominal bloating for which there is no evidence of detectable organic disease. Suggested etiologies include gut motility and psy­chological disorders as well as psycho-physiological phenomena and colonic fermentation (115).

A large proportion of patients have periods characterized by sudden and unforeseeable changes in the two main symptoms, constipation and diarrhea, even within a few days (115). It is very likely that the syndrome represents different groups of patients with probably different pathogenesis. Irritable bowel syndrome may follow gastroenteritis and may be associated with an abnormal gut flora and with food intolerance (117). The fecal microflora in some of these patients has been shown to be abnormal with higher numbers of facultative organ­isms and low numbers of lactobacilli and bifidobacteria (115).

Bacteria are the major component of formed stools and are influenced by substrates ar­riving with the ileal affluent. Stool production is re­lated to quantitative and qualitative aspects of the colonic microflora and nearly 80% of the fecal dry weight consists of bacteria, 50% of which are viable.

Although there is no evidence of food allergy in irritable bowel syndrome, food intolerance has been identified and exclusion diets are beneficial to many of these patients. Food intolerance may be caused by an abnormal fermentation of food residues in the colon, as a result of disruption of the normal flora (115).

Some reports suggest that probiotics play a role in regulating the motility of the digestive tract (114). This may result in improvements in pain and flatulence in response to probiotic administration (115).

To assess whether preceding gastroenteritis or food intolerance were associated with colonic malfermentation, King et al. (117) conducted a cross­over controlled trial with a standard diet and an ex­clusion diet matched for macronutrients in six fe­male patients with irritable bowel syndrome and six female controls.

In this study fecal excretion of fat, nitrogen, starch, and nonstarch polysaccharide was measured during the last 72 hours of each diet. The total excretion of hydrogen and methane were col­lected over 24 hours in purpose-built 1.4 m3 whole body calorimeter. Breath hydrogen and methane excretion were measured for 3 hours after 20 g oral lactulose. The maximum rate of gas excretion was significantly greater in patients than in controls. The total gas production in patients was not greater than in controls, whereas hydrogen production was higher.

After lactulose, breath hydrogen was greater on the standard than on the exclusion diet. This means that colonic-gas production, particularly of hydrogen, is greater in patients with irritable bowel disease than in controls, and both symptoms and gas production are reduced by an exclusion diet. This reduction may be associated with alterations in the activity of hydrogen-consuming bacteria. It was therefore concluded that fermentation may be an important factor in the pathogenesis of this syndrome (117).

Spiller et al. (118) studied the intestinal perme­ability (Iactulose/mannitol ratio) and histological and immunological features in rectal biopsy specimens in 21 patients who had acute Campylobacter enteritis, 10 patients with postdysenteric irritable bowel syndrome and 12 asymptomatic controls. They found that the increased enteroendocrine cell counts, T lymphocytes, and gut permeability, which may survive for more than a year after Campylobacter enteritis, contribute to post-dysenteric irrita­ble bowel syndrome (118), thus offering a rationale to use probiotics for several months after the infectious episode.

VSL3 in patients with Irritable Bowel Syndrome

The effect of the probiotics was studied by Brigidi et al. (119) in a clinical trial in which 10 patients suffering from this syndrome were adminis­tered the VSL#3 probiotic preparation. The results indicated that the administration of VSL#3 im­proved the clinical picture and changed the com­position and biochemistry of fecal microbiota. The exact mechanisms of the positive effects are not known. The selection of patients may have had an important role in detecting the positive effects. Whether the induction of a significant increase in lactobacilli, bifidobacteria, and S. thermaphilus con­tributed to the regulation of the motility disorders or the increase in fecal B-galactosidase with a decrease in urease content indicate that a good response requires further study. The importance of this study is that it showed that the measurement of specific parameters and changes in the specific microflora was possible.

Kim et al. (120) investigated the effects of VSL#3 on gastrointestinal transit and symptoms of patients with Rome II-Irritable Bowel Syndrome with predominant diarrhea. Twenty-five patients with diarrhea-predominant Irritable Bowel Syndrome were randomly assigned to receive VSL3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period.

Pre- and post-treatment gastro-intestinal transit measurements were performed in all patients. The patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit endpoint. There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy.

The differences in abdominal bloating scores between treatments were borderline significant. Abdominal bloating was reduced with VSL3, but not with placebo. Furthermore, VSL#3 had no effects on individual symptoms such as abdominal pain, gas and urgency. VSL3 was well tolerated by all patients, and thus it seems to relieve the abdominal bloating in patients with diarrhea-predominant Irritable Bowel Syndrome (120).

21 Probiotics in Crohn’s Disease

Probiotics in Crohn’s Disease

The therapeutic role of probiotics in the prevention of postoperative recurrence of Crohn’s disease has been reported in some studies. Gampieri et al. (111) studied the effects of VSL3 in a randomized, investigator-blind trial. Forty patients with curative resection randomized within 1 week post surgery were divided into two groups of 20 patients. One group received mesalazine 4 g/day for 1 year and the other group received rifaximin 1.8 g/day for 3 months followed by VSL#3 6 g/day for 9 months. The endoscopic activity was assessed after 3 and 12 months. In the mesalazine group, eight patients had severe endoscopic recurrence after 3 months as well as after 12 months, whereas in the group with rifaximin and VSL3, two patients had a severe recurrence after 3 months and two patients after 12 months.

These results suggested the efficacy of the combination of a nonabsorbable antibiotic with a highly concentrated probiotic preparation in the prevention of severe endoscopic recurrence of Crohns disease after surgical resection.

In a pilot study Guandalini et al (112) investigated the possible effect of Lactobacillus GG in children with active Crohns disease. Four male patients with a median age of 14.5 years (range 10-18) were enrolled. In terms of clinical outcome, the patients showed significant improvement. In three patients receiving Lactobacillus GG, it was possible to taper the dose of steroids.

In a third published study using Lactobacillus GG this effect could not be confirmed. Forty-five patients were randomized to receive Lactobacillus GG 12 billion GFU/day (23 patients) or placebo (22 patients). A clinical remission after 52 weeks was seen in 15 of the 23 patients with Lactobacillus GG (83.3%) and in 17 of the 22 patients with placebo (89.4%).

Mild endoscopic activity was seen in nine of the 15 patients with remission in the Lactobacillus GG group (60%) and in six of the 17 patients with remission in the placebo group (35.3%). This study failed to show effectiveness in the postoperative prevention on Crohn’s disease (113). More studies are therefore necessary. The limited experience indicates that different probiotics have different capacity to prevent intestinal inflammation.

20 Pouchitis & Probiotics

Probiotics in Pouchitis

Pouchitis is a nonspecific inflammation of the ileal reservoir, that may appear after surgery for ulcerative colitis, and results in various clinical symptoms. It is a well-recognized long-term complication of restorative proctocolectomy.

The risk of pouchitis increases in patients with a history of extra-intestinal manifestations, primary sclerosing cholangitis, positive serology for perinu­clear anti neutrophil cytoplasmic antibodies, and backwash ileitis (107).

Pouchitis is associated with bacterial over­growth and dysbiosis, and antibiotics represent the first-choice treatment. The distal ileum and the large bowel, the sites with the highest bacterial concen­tration, are the most frequently affected by inflammation. Enteric bacteria or their products have been detected within the inflamed mucosa.

A significant decrease of lactobacilli and bifidobacteria concentra­tions has been found in ulcerative colitis, Crohn’s disease and pouchitis. Lactobacilli as maintenance showed less frequent relapses of pouchitis than those using placebo. Diversion of the fecal stream in the small and large intestine reduces the activity of the inflammation. The luminal contents and purified bacterial products added to isolated intestinal loops trigger systemic and local signs of inflammation.

In a study by Campieri et al. (103), seven patients, after clinical, endoscopic, and histological diagnoses of inflammation of the ileal pouch anal anastomosis with a pouchitis disease activity index (PDAI) > 7, were treated with 2 g/day of rifaximin (a non absorbable antibiotic) and 1 g/day of ciprofloxacin for 1 month.

All patients went into remission during this month, as judged by clinical, endoscopic and histological examination.

After remission, all seven patients were treated with the highly concentrated probiotic mixture VSL3 for nine months. No patient had a relapse in this period. All patients who received placebo had a relapse.

Probiotics in the maintenance of remission of chronic Pouchitis

Gionchetti et al. (108) evaluated the efficacy of VSL#3 in the maintenance of remission of chronic pouchitis. Forty patients in clinical and endoscopic remission were randomized to receive either VSL3 6 g/day, or an identical placebo for 9 months.

The patients were assessed clinically every month and endoscopically and histologically every 2 months or in the event of relapse. Three patients (15%) in the VSL#3 group had relapses within the 9-month follow-up period, compared with 20 (100%) in the placebo group. In the VSL3-treated group, the fecal concentration of lactobacilli, bifidobacteria, and S. thermaphilus increased significantly from base­line levels. These results suggested that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic pouchitis.

Probiotics in the prevention of the onset of Pouchitis

A positive effect of VSL3 in the prevention of pouchitis has been reported by Gionchetti et al. (109), who compared probiotic therapy with VSL#3 versus placebo in the ability to prevent the onset of acute pouchitis during the first year after ileal pouch­anal anastomosis. Forty patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were randomized to receive either VSL3 or an identical placebo immediately after ileostomy closure for 1 year.

Both groups consisted of 20 patients. The patients were assessed clinically, endoscopically, and histologically after 1, 3, 6, 9 and 12 months. Health-related quality of life was assessed using the Inflammatory Bowel Disease Ouestionnaire (IBDO). Two of the 20 patients (10%) treated with VSL3 had an episode of acute pouchitis compared with eight of the 20 patients (40%) treated with placebo.

Treatment with VSL#3 determined a significant improvement in IBDQ score, which was not the case with placebo. During treatment with V8L3, fecal concentration of lactobacilli, bifidobacteria, and S. salivarius increased significantly.

The fecal concentration of Bacteroides, clostridia, coliforms, and enterococci were not modified. This suggested that the beneficial effect was not mediated by the suppression of the endogenous flora. The treatment with V8L#3 was effective in the prevention of the onset of acute pouchitis and improved the quality of life of patients with ileal pouch anal anastomosis.

As mentioned above, probiotic bacteria do not survive for long, and rapidly disappear as soon as the treatment is stopped. Therefore, prophylactic probiotic therapy of pouchitis might require longterm treatment and might not be indicated for all patients.

For this reason, V8L3 would be highly beneficial for patients at high risk of chronic pouchitis. In these cases prophylactic probiotics may be administered, pouch function improved and their quality of life after ileal pouch anal anastomosis could be maintained. Katz et al. (107) suggested that probiotics should be used for maintaining remission in chronic pouchitis and as prophylaxis against pouch inflammation in high-risk patients. Although preliminary results suggest that high doses V8L#3 may improve active pouchitis, probiotic therapy seems to be more effective to prevent mucosal inflammation than to treat it.

Kuisma et al. (110) investigated the efficacy of Lactobacillus GG supplementation as primary therapy for pouchitis and its effect on the microbial flora. Twenty patients, with a previous history of pouchitis and endoscopic inflammation were recruited for a prospective, randomized, double-blind, placebo-controlled trial of Lactobacillus GG supplementation.

Ten patients received Lactobacillus GG and 10 placebo, in two gelatin capsules b.i.d. for 3 months. Quantitative bacterial culture of fresh fecal samples and biopsies taken from the pouch and afferent limb was performed before and after supplementation. Lactobacillus GG supplementation was found to change the pouch intestinal flora by increasing the ratio of total fecal lactobacilli to total fecal anaerobes and enhancing the frequency of lactobacilli-positive cultures in the pouch and afferent limb mucosal biopsy samples.

Only 40% of patients were colonized with Lactobacillus GG, and no differences were observed between the groups with regard to the mean PDAI or the total anaerobes or aerobes of fecal or tissue biopsy samples.

Thus, a single-strain probiotic bacterium supplement of Lactobacillus GG changed the pouch intestinal bacterial flora, but was ineffective as primary therapy for a clinical or endoscopic response. More clinical trials are needed to evaluate the right placement and dosage of probiotics within a treatment regimen for pouchitis.

19 Probiotics in Ulcerative Colitis

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.

18 Probiotics in IBD

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:

  • immunologic,
  • genetic and
  • psychological.

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).

17 Probiotic use in Diarrhea

Probiotics in Diarrhea

Antibiotic-associated diarrhea

Several reports exist on the benefits of probiotics in this common complication of the use of antibiotics. For example, in the prevention of antibiotic-associated diarrhea, 45 patients being treated with antibiotics were given, concurrently, one capsule of either Enterococcus SF68 or placebo for 7 days (10 centers) twice daily.

Enterococcus SF 68 was effective in reducing the incidence of antibiotic-associated diarrhea compared to placebo (8.7% compared to 27.2%, respectively) (96). Important here is the evidence that Enterococcus SF68 has been withdrawn because of the risk of antibiotic resistance transfer. Not all reports are similarly encouraging but the type of probiotics used may be important in achieving results.
Probiotics in acute diarrhea

Multiple studies in children have shown that Lactobacillus, administered orally, may have antidiarrheal properties. To determine the effect of Lactobacillus GG on the course of acute diarrhea in hospitalized children, a prospective, placebo-controlled, triple-blind clinical trial was carried out in Pakistan. Forty children (mean age, 13 months) received either oral Lactobacillus GG (n = 21) or placebo (n = 19) twice daily for 2 days, after rehydration in addition to the usual diet.

The clinical course of diarrhea was followed during the treatment period. The features for admission into the study groups were similar and were characterized by severe diarrhea, malnutrition and inappropriate management before presentation. Response was evident on day 2, when the frequency of both vomiting and diarrhea was less in the Lactobacillus group. In those patients with acute nonbloody diarrhea (n = 32), the percentage of children with persistent watery diarrhea at 48 hours was significantly lower in the Lactobacillus group (31 % versus 75%). No significant difference was observed after 48 hours in those with bloody diarrhea (97).

Van Niel et al. (98) conducted a meta-analysis of randomized, controlled studies to assess whether treatment with Lactobacillus improved clinical outcome in children with acute infectious diarrhea. They conducted a search in bibliographic databases of traditional biomedical as well as complementary and alternative medicine literature published between 1966 and 2000. The original search yielded 26 studies, nine of which met the criteria. A reduction of 0.7 days in diarrhea duration and a reduction of 1.6 stools for diarrhea frequency was attained on day 2 of treatment in the participants who received Lactobacillus compared to those who received placebo. A preplanned subanalysis suggested a dose-effect relationship. The results of this meta-analysis suggested that Lactobacillus is safe and effective as a treatment for children with acute infectious diarrhea.
Probiotics in rota virus diarrhea

Rotavirus was discovered in children with gastroenteritis by Bishop et al. in 1973 (99). This agent causes widespread morbidity and 870,000 deaths worldwide each year. As Bishop said, “after doing a lot of background reading, it became clear that there probably was an infectious agent but we could not get anything to grow in culture”. Bishop et al. (99) participated in the development of vaccines against rotavirus, the first of which was licensed for use in the USA in 1998.

The effect of orally administered lactobacilli on acute rotavirus diarrhea was tested by Isolauri et al. (100) in 42 well-nourished children aged 5-28 months. After oral rehydration, the patients received human L. casei strain GG 1010 CFU twice daily for 5 days. The control group was not given lactobacilli. Lactobacillus GG was found in the feces of 83% of the group with L. casei strain GG. The diarrheal phase was shortened in that group. The dietary supplementation with lactobacilli significantly influenced the bacterial enzyme profile. Urease activity during diarrhea transiently increased in the control group but not in the group receiving L. casei strain GG. No intergroup differences were found in B-glucuronidase, B-glucosindase, and glycocholic acid hydrolase levels.

Therefore, Isolauri et al. suggested that rotavirus infection gives rise to biphasic diarrhea, the first phase being an osmotic diarrhea and the second associated with overgrowth of specifically ureaseproducing bacteria. Oral bacteriotherapy appears to be a promising means to counteract the disturbed microbial balance.

To evaluate the ingested strain’s adherent properties and ability to inhibit murine rotavirus infection, Duffy et al. (101) administered human Bifidobacterium sp. strain bifidum to BALB/c lactating mice (n = 58) and their litters (n = 327 pups). ELISA and anaerobic bacteriologic techniques were used to measure murine rotavirus shedding and colonization of Bifidobacterium in the small intestine.

At 1316 days of gestation, pregnant dams (and their expected litters) were randomly assigned to one of four experimental groups as follows: normal controls; B. bifidum-treated only; murine rotavirus-infected only; and B. bifidum-treated plus murine rotavirus-infected dams and litters. During the acute phase of diarrhea, 80% of small-intestine cultures in B. bifidum-treated litters were positive for the ingested B. bifidum strain compared to 24% of fecal cultures.

The examination of tissue cross sections under electron microscopy revealed the ingested B. bifidum strain survived passage through the upper gastrointestinal tract and adhered to the small-intestine epithelium. After the administration of the high dose of virus, diarrhea developed in all pups, but onset was significantly delayed in B. bifidum-treated plus

Murine rotavirus-infected litters compared to litters infected with murine rotavirus only. B. bifidum-treated plus murine rotavirus-infected pups demonstrated a significant reduction in murine rotavirus shedding compared with litters challenged with murine rotavirus only at day 2-10 after inoculation. More direct studies are needed to assess the mechanisms by which this anaerobe may modify the course of murine rotavirus infection at the level of gut epithelium.

Qiao et al. (102) evaluated the potential synergistic effects of Bifidobacterium spp. (B. bifidum and B. infantis), with or without prebiotic compounds (arabi no-galactan, short-chain fructooligosaccharide, iso-maltodextrins), on modulating the course of rhesus rotavirus infection, as well as their ability to mediate the associated mucosal and humoral immune responses. Therefore, they fed these species orally to pups. Rotavirus-specific IgA and IgG in serum, rotavirus antigen, and specific IgA in feces were measured by ELISA. Mucosal total IgA and IgG levels were determined in Peyer’s patches by flow cytometry.

Significantly delayed onset and early resolution of diarrhea were observed in bifidobacteria-treated, rhesus rota virus-infected mice compared with rhesus rotavirus-infected control mice. They saw that supplementation with prebiotic compounds did not shorten the clinical course of diarrhea more than that observed with bifidobacteria treatment alone. Rotavirus-specific IgA in feces was elevated 16-fold on day 5 postinfection in bifidObacteria-treated, rhesus rotavirus-infected mice compared with the rhesus rotavirus-infected only group. In addition, the level of rotavirus-specific IgA in serum was fourfold higher in bifidobacteria-treated, rhesus rota virus-infected litters versus mice challenged with rhesus rotavirus alone on 28 and 42 days postinfection.

They found no enhancement of the immune response in rhesus rotavirus-infected mice that were treated with both bifidobacteria and prebiotic compounds over those treated with bifidobacteria alone. These findings suggested that bifidobacteria may act as an adjuvant by modulating early mucosal and strong humoral rotavirus-specific immune responses, and mitigate the severity of rotavirus-induced diarrhea (102).

16 Treatment in vitro

Probiotic Treatment in vivo in Experimental Animals and in Man

There is some evidence suggesting that probiotics prevent infections caused by enteropathogens. About 47 different Lactobacillus strains have been tested in vitro for their ability to inhibit growth of a number of pathogens. Among the tested strains, L. rhamnosus 19070-2, L. reuteri DSM 12246, and L. rhamnosus LGG were identified most frequently in fecal samples; they were found in 10, eight, and seven of the 12 samples tested during the intervention period, respectively, whereas reisolations were less frequent in the washout period. Survival and reisolation of the bacteria in vivo appeared to be linked to pH tolerance, adhesion, and antimicrobial properties in vitro (94). The majority of the strains inhibited Yersinia entero colitica and Bacillus cereus and a few exhibited anti-microbial activities toward Staphylococcus aureus and Salmonella enterica serovar typhimurium (8).

Lactic acid bacteria in general may inhibit the growth of enteropathogens such as E. coli, H. pylori, Listeria monocytogenes, Salmonella spp. and others. This antagonistic activity is mediated either directly by the production of inhibitory substances such as lactic acid, hydrogen peroxide, bacteriocins, a-hydroxypropionaldehyde and other unidentified compounds or by competing with the pathogen for binding sites on the epitheliaL cell surface.

Another criterion for effective probiotic organisms is the adhesion to epithelial cells, a characteristic of several lactobacilli and some bifidobacteria. The factors mediating cell adhesion are still unknown. It has been suggested that proteinaceous factors are involved. Lipoteichoic acid participates in the adhesion of L. johnsonii La1 to epithelial Caco-2 cells (95).

A human feeding study conducted in 80 healthy volunteers showed that yogurt may be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. The investigators in Cork, Ireland, developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host, such as modulation of gastrointestinal tract microflora (18).