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Inflammatory Bowel Disease IBD Diagnosis & Treatment

Digestive Disease Week 2003 - Dr. Richard Fedorak, M.D.

According to Dr. Richard Fedorak, M.D., who presented studies on probiotics at Digestive Disease Week, 'the possibility of using this natural treatment for patients with IBD is a very exciting avenue of investigation.' He went on to explain their significance in IBD. "Bacteria adhere to the lining of the colon like icing on a cake," says he said. "Probiotics are able to negotiate through this layer of bacteria and layer themselves against the epithelial surface. They prevent bacteria from adhering to or crossing the epithelium [lining of the intestine]."

He cited a randomized controlled trial of patients with pouchitis who were treated with a probiotic preparation. Pouchitis is a complication that occurs after surgery to remove the colon. Surgeons create a "pouch" from the lower end of the small intestine so that normal bathroom habits can be retained. The pouch sometimes becomes infected and inflamed. This trial showed that probiotics were able to prevent recurrent episodes of pouchitis in 85% of treated patients (compared to 0% of placebo-treated patients).

"Another important aspect of probiotics is their antimicrobial activity," added Dr. Fedorak. "probiotics produce a number of agents that destroy bacteria."

"It's very likely that there will be a preventative role for probiotics in IBD, and perhaps a role in addition to other therapies," he concluded.

A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome.

Niedzielin K, Kordecki H, Birkenfeld B.

Irritable bowel syndrome (IBS) is a widespread functional disorder of the digestive tract. Its aetiology is unknown and therapeutic options are limited. Recent reports suggest that probiotics may have a role in regulating the motility of the digestive tract.

To assess the efficacy of Lactobacillus plantarum 299V (LP299V) in patients with IBS.

Forty patients were randomized to receive either Lactobacillus plantarum LP299V in liquid suspension (20 patients) or placebo (20 patients) over a period of 4 weeks. Clinical examination was performed at baseline and at the end of the study. Additionally, patients assessed their symptoms by applying a scoring system.

All patients treated with Lactobacillus plantarum LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group (P = 0.0012). There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo (P = 0.17). With regards to all irritable bowel syndrome IBS symptoms an improvement was noted in 95% of patients in the Lactobacillus plantarum LP299V group vs 15% of patients in the placebo group (P < 0.0001).

Lactobacillus plantarum LP299V seems to have a beneficial effect in patients with IBS. Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS.

PMID: 11711768 [PubMed - indexed for MEDLINE]

Several probiotic formulas contain Lactobacillus plantarum. These include:

Symposium Highlights the Clinical Use of Probiotics, Prebiotics & Enzymes

Reno, NV, November 15, 2008

On November 14th and 15th, the University of Nevada School of Medicine hosted the Second Annual Symposium on Probiotics, Prebiotics, and Enzymes: Clinical Applications in Human Health. An international faculty provided attendees with recent research and hypotheses on the mechanisms of action and use of probiotics, prebiotics, and digestive enzymes to maintain and improve both physical and mental health.

Dr. Gary Elmer, Professor Emeritus of Medicinal Chemistry at the University of Washington and authority on the use of probiotics to prevent and manage antibiotic-associated diarrhea and Clostridium difficile disease, provided an introduction to probiotics and sought to dispel the common myths that probiotics are not well-studied and are only effective for diarrheal illnesses.

He emphasized that adequate probiotic doses are essential to ensure good clinical outcomes and noted that recovery of organisms from stool cultures does not always correlate with benefit. Dr. Elmer called for enhanced funding of basic research on probiotics and optimization of existing therapies with proven probiotics.

Dr. Charalabos Pothoulakis, Professor of Medicine at the David Geffen School of Medicine at UCLA and Director of the UCLA Inflammatory Bowel Disease Center presented two lectures. On day one, he focused on probiotic mechanisms of action reviewing research performed in his laboratory showing that beneficial effect of Saccharomyces boulardii in C. difficile-associated disease is due in part to prevention of inhibitory kBa degradation.

This effect prevents C. difficile toxin A from activating nuclear factor-kB (NF-kB), which is how toxin A causes colonocyte death. Dr. Pothoulakis also reported that supernatant from S. boulardii culture inhibits inflammatory interleukin-8 production and blocks NF-kB-mediated gene transcription.

He reviewed evidence that supernatant from a multispecies probiotic formulation inhibits tumor necrosis factor-a (TNF-a) stimulation of NF-kB and presented evidence that Lactobacillus rhamnosus GG produces two proteins that rescue colonocytes from TNF-a induced damage and apoptosis.

On day two, Dr. Pothoulakis reviewed the evidence for the role of probiotics in inflammatory bowel disease and concluded that a multispecies preparation has clear benefit in pouchitis complicating ulcerative colitis and that S. boulardii has benefit by reducing production of proinflammatory cytokines.

Dr. Maria Oliva-Hemker, Chief of the Division of Pediatric Gastroenterology and Nutrition at Johns Hopkins University School of Medicine, discussed the neonatal acquisition of a normal gastrointestinal microflora. She outlined factors that may disrupt an infant's microbiota and the health consequences of such disruptions, which include gastrointestinal disturbances and immune dysfunction.

Dr. Maria Oliva-Hemker reviewed the research supporting the use of probiotics to reduce the incidence of necrotizing enterocolitis (NEC) in preterm, low-birth weight infants and concluded that L. rhamnosus GG, Bifidobacterium infantis, B. bifidum, and S. boulardii have all shown benefit and, most importantly, proven to be safe in this highly vulnerable patient group.

Drs. Katzman and Lord concluded the first day of the Symposium with their thought-provoking lectures. Dr. Martin Katzman, Assistant Professor of Psychiatry at the University of Toronto and Director of the Stress, Trauma, Anxiety, Rehabilitation and Treatment Clinic presented the intriguing hypothesis that probiotics may have a role in the treatment of patients with depression and anxiety.

Dr. Richard Lord, Chief Science Officer of the Metametrix Institute, reviewed the clinical laboratory use of DNA amplification of microbial genetic material isolated from stool samples to assess the composition of the gastrointestinal microbiota and to detect pathogenic organisms and parasites. The technique avoids the well-known limitations of traditional stool cultures although the precise role of the testing in guiding probiotic selection is not yet clear.

Dr. Sandra Macfarlane, Senior Research Scientist for the Division of Pathology and Neuroscience at the University of Dundee, presented cutting edge research on the use of prebiotics used alone or in combination with probiotics (synbiotics) to modify gastrointestinal biofilms.

Biofilms are communities of sessile microorganisms residing within a self-produced matrix of exopolymers. Microbes prefer living within biofilms which provide them protection from dislodgement, predation, host immune responses, and antimicrobial agents. Pathogens living within biofilms are highly resistant to efforts to eradicate them and pathogenic biofilms may be a source of recurrent disease.

Dr. Macfarlane noted that microbes inhabiting biofilm are more efficient at fermenting long-chain polysaccharides than are free-living luminal bacteria, which appear to chiefly ferment oligosaccharides. Microorganisms within biofilms in the mucus layer overlying the intestinal mucosa are more likely to interact with the host immune system and these interactions may be healthful or harmful depending on the organisms involved.

She noted data showing that microbial gastrointestinal biofilm communities in patients with ulcerative colitis contain significantly fewer bifidobacteria and higher numbers of anaerobic gram-positive cocci, peptostreptococci, enterococci, and enterobacteria. Dr. Macfarlane reviewed both in vivo and in vitro evidence that the prebiotic inulin can significantly increase intestinal biofilm bifidobacterial populations while simultaneously decreasing biofilm populations of Clostridium, Bacteroides, Fusobacterium, and Enterobacteraceae species, and at the same time inhibit pathogen activity and reduce C. difficile toxin concentrations.

This evidence led to her hypothesis that treating ulcerative colitis patients with a combination of prebiotics and probiotics could be beneficial. She concluded by presenting data from her recent study on the use of B. longum and oligofructose-enriched inulin in patients with ulcerative colitis. The synbiotic caused a marked increase in bifidobacteria populations, a striking reduction mucosal human b-defensin levels, and significant improvements in colonic mucosal inflammation seen on colonoscopy.

Dr. Gary Gray, Professor of Medicine, Emeritus at Stanford University School of Medicine and Director of the Stanford Celiac Sprue Management Clinic, reviewed the pathophysiology of celiac disease and presented his research on the peptidase treatment of dietary gluten.

He found that an endopeptidase isolated from barley reduced fat malabsorption in patients with celiac disease in remission. Dr. Andrew Bruce, Emeritus Professor of Urology at the University of Toronto, lectured on the use of a probiotic formulation containing L. reuteri RC-14 and L. rhamnosus GR-1 to treat vaginal dysbiosis and reduce the incidence of recurrent urinary tract infections in women.

He noted that oral probiotic use provides benefit and the organisms do not have to be administered vaginally.

Dr. John Morton, Associate Professor of Surgery and director of the bariatric surgery program at Stanford University, presented fascinating data on the potential role of the gastrointestinal microbiota in the growing worldwide epidemic of obesity.

He noted that the rapid spread of obesity in the United States since 1997 has led many investigators to question whether an infectious agent or agents could be involved. It has been established that obesity spreads within networks of friends and families and that treating obese parents with bariatric surgery can result in weight loss in their children.

The gut microflora generates 30% of a person's daily caloric intake so the presence of microbes more efficient at extracting energy from the diet has been hypothesized to contribute to overweight and obesity. A relation between alterations in gastrointestinal microbiota and obesity was first noted by Dr. Jeffrey Gordon's group at Washington University who found that obese mice and people had fewer numbers of bacteria in the Division Bacteroidetes and greater numbers in the Division Firmicutes than did their lean siblings or controls.

Furthermore, this alteration in gut microbiota proved to be transmissible in mice suggesting that disorders in intestinal microbiota could be passed from one person to another resulting in the spread of obesity.

Dr. Marko Kalliom's group in Finland has published data showing that alterations in gut microbiota during early childhood predictoverweight and obesity in later life. These alterations consist of reduced populations of bifidobacteria and increased numbers of Staphylococcus aureus.

Dr. Morton expounded on the exciting results of a study he recently concluded in which L. acidophilus was administered to patients following Rouxen- Y bariatric surgery. The study was undertaken to assess whether a probiotic could reduce the incidence of intestinal bacterial overgrowth in these patients, which it did.

However, an unexpected finding was that compared to placebo, patients receiving the probiotic experienced significantly greater weight loss following surgery. This is the first clinical trial to suggest that probiotics may enhance weight loss. Dr. Morton plans a large multicenter trial to follow up on this potentially highly important observation.

See Probiotics Article by Jule Klotter

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