Several new studies published in major medical journals over the last 6 months are strengthening the scientific support for use of probiotics as treatment for irritable bowel syndrome, ulcerative colitis and chronic liver diseases.

The new data show, among other findings, that probiotics can greatly lessen symptoms of IBS and colitis, in many cases producing complete endoscopically confirmed remissions. There is also compelling new evidence that probiotics can improve hepatic function in people with several different types of liver disease. The studies reflect a growing interest in probiotics among conventional gastroenterologists.

VSL#3 Probiotic Combo Tames UC

Investigators from the Department of Agricultural, Food and Nutritional Science at the University of Alberta, Edmonton tested a powdered, freeze-dried probiotic combination called VSL#3 in 34 ambulatory adults with mild to moderate ulcerative colitis that did not respond to conventional drug therapy. VSL#3 is manufactured by Sigma-Tau Health Sciences, an Italian pharmaceutical/nutraceutical company.

The VSL#3 formulation is a combination of eight probiotic bacterial species: Lactobacillus acidophilus, L. bulgaricus, L. casei, L. plantarum, Bifidobacteria breve, B. infantis, B. longum, and Streptococcus salivarius subsp. Thermophilus.

The patients in this study took two sachets of the VSL#3 powder, each containing 900 billion viable lyophilized bacterial cells, twice daily for a total of 6 weeks. The powder was dissolved in water or mixed into cold foods. The researchers assessed patients via endoscopy at baseline and at the conclusion of the trial. They also used DNA sequencing of 16S rRNA to confirm the presence of VSL#3 bacterial species in the patients’ GI mucosal biopsy samples.

	The four images to the left are baseline endoscopic views from a patient with ulcerative colitis who did not respond to conventional drug therapy. The images to the right are from the same patient after six weeks of treatment with the VSL#3 probiotic combination. Images reprinted with permission of Richard Fedorak, MD, University of Alberta.

Eighteen of the 34 patients (53%) had full remissions based on score reductions on the Ulcerative Colitis Disease Activity Index (UCDAI). An additional eight patients (24%) had strong clinical responses as indicated by a decrease in UCDAI scores. Three patients had no response, and an additional three had a worsening of UCDAI scores (Bibiloni R, et al. Am J Gastroenterol 2005 Jul; 100(7): 1539–46). The outcomes were confirmed endoscopically.

The investigators were also able to confirm the presence of some of the bacterial species from the VSL#3 supplement in intestinal biopsy specimens indicating that the probiotic did indeed reach the target site. They noted there were no adverse events associated with the probiotic treatment, other than mild bloating in some patients.

The findings corroborate earlier studies showing that VSL#3 could prevent or reduce flare-ups of refractory pouchitis (Mimura T, et al. Gut 2004; 53: 108–14; Gionchetti P, et al. Gastroenterology 2003; 124: 1202–9).

“Our results suggest that oral administration of high doses of VSL#3 may effectively treat ulcerative colitis and is associated with no serious adverse effects,” wrote Dr. Rodrigo Bibiloni, who led the ulcerative colitis study. He added that a randomized, placebo controlled study of VSL#3 is now underway.

A Role in Liver Disease Treatment

Concurrent with Dr. Bibiloni’s study, researchers at the Inter-University Research Center of Foods, Nutrition and the Gastrointestinal Tract, Naples, published an open-label study indicating that VSL#3, taken daily for 3 months, could markedly reduce production of inflammatory cytokines such as TNF-α, IL-6, and IL-10 in patients with alcoholic liver cirrhosis.

They also found the probiotic combination could reduce malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), key markers of lipid peroxidation, while increasing plasma S-nitrosothiols, an indicator of nitric oxide production, in patients with alcoholic cirrhosis, non-alcoholic fatty liver disease or chronic hepatitis C (Loguercio C, et al. J Clin Gastroenterol 2005; 39(6): 540–3).

“The liver continuously receives blood from the gut through the portal system; therefore there is a close and constant relationship between the gut and the liver. Animal studies have shown that translocation of bacterial products from the intestinal lumen to the mesenteric circulation and the lymphatics activates the Kupffer cells in the liver and induces regional and systemic production of proinflammatory cytokines, enhances production of free radical species and activates nitric oxide synthase in the splanchnic area,” wrote Carmela Loguercio, MD, the lead investigator.

“Intestinal bacteria also produce ethanol and acetaldehyde. Thus gut-derived endotoxins and metabolites may both contribute to the evolution of alcohol or obesity-related liver steatosis to steatohepatitis and fibrosis, as well as the onset of portal hypertension.”

The probiotic species in a preparation like VSL#3 modulate the gut flora and reduce the number of pro-inflammatory species, thus slowing progression of liver disease. The current findings are in keeping with an earlier study showing probiotics could improve liver function in patients with alcoholic and non-alcholic liver disease (Loguercio C, et al. Am J Gastroenterol 2002; 97: 7–9). Dr. Loguercio concludes that the beneficial effects of VSL#3 on liver function tests, the low cost, and the good tolerability all suggest that probiotics ought to be considered as a complementary therapy for liver disease patients.

“Baby Bacteria” Beats IBS

The VSL#3 studies came close on the heels of a trial from the University College of Cork, Ireland, that compared two different probiotic bacteria, B. infantis and L. salivarius against placebo in the treatment of 77 adults with IBS. Patients were randomized to receive one of the two probiotics, taken as a daily dose of 1 × 10¹⁰ live bacterial cells in a malted milk drink, or the malted milk alone for 8 weeks. The patients were instructed to record their symptoms every day. The investigators also assessed quality of life, stool microbiology, and blood levels of interleukin (IL)-10 and 12. The ratio of these cytokines, released by peripheral blood mononuclear cells, indicates the level of inflammatory activity.

They found that for all symptoms, with the exception of bowel movement frequency and consistency, patients receiving B. infantis experienced greater reductions in symptom scores, composite abdominal pain scores, bloating and distention, and bowel movement difficulty, compared with those taking the L. salivarius or the placebo (O’Mahony L, et al. Gastroenterology 2005 Mar; 128(3): 541–51).

At baseline, all patients showed abnormal IL-10 to IL-12 ratios indicating a proinflammatory state of the TH1 type. This was entirely normalized in the patients taking the B. infantis probiotic. The investigators noted that the level of symptom relief achieved with B. infantis is comparable to what is usually seen with tegaserod (Zelnorm) or alosetron (Lotronex), two state of the art drugs for IBS. As with the VSL#3 study, there were no adverse effects associated with the probiotic therapy.

The Cork researchers believe the observed symptom reductions reflect the probiotic’s anti-inflammatory effect. “The symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine, suggesting an immune-modulating role for this organism.”

B. infantis is one of the most prevalent bacterial species in the gut flora of healthy, breast-fed human infants. Babies typically acquire the organism, along with other species of Bifidobacterium, from their mothers during vaginal birth and through breast-feeding. It is a particularly important organism for establishing a healthy gut ecology in early life because it secretes a sticky carbohydrate compound that allows it to bond tightly to the intestinal wall, helping it to “crowd out” undesirable organisms.

Unfortunately, there is evidence that over the last decades, the prevalence of this important “baby bacterium” has been declining in the intestinal tracts of babies. This reflects a number of trends including the increase in cesarean and premature deliveries, the increased use of antibiotics and other prescription drugs in babies and young children, and also environmental contaminants and toxins, detrimental to the organism, that are passed to babies from their mother’s milk. This decline in B. infantis may be an important contributor to the increase in inflammatory disorders among babies and young children.

In an effort to remedy this situation, Natren, one of the nation’s leading probiotic companies, recently introduced a product called LifeStart, which provides 1 billion colony-forming units of B. infantis. The product is available as a powder in a cow’s milk or goat’s milk base, and is designed to be given to infants and also taken by nursing mothers, with the objective of improving the newborn’s gut flora.

Probiotics: Not So “Alternative” Anymore

Mainstream scientific interest in probiotics is likely to continue in the coming years, as clinicians increasingly recognize the importance of the gut microflora in maintaining health. Earlier this summer, the journal, Practical Gastroenterology, published an excellent overview article entitled “Probiotics and the Management of Adult Clinical Gastrointestinal Disorders,” that summarizes what is now known about the use of probiotics in the management of IBS, ulcerative colitis, traveler’s diarrhea, Helicobacter pylori infection, and prevention of colorectal cancer.

“There is proven benefit in the prophylaxis and treatment of postoperative pouchitis, prevention of recurrent C. difficile associated diarrhea and treatment of infectious diarrhea in children,” writes Dr. D.D. Demeria, the paper’s author. “Evidence is emerging for the use of probiotics in other gastrointestinal infections such as in IBS and in both ulcerative colitis and Crohn’s disease.”

It seems that the use of probiotics, once considered a “fringe” modality, is no longer so “alternative.” As Dr. Demeria notes, “the spectrum of the clinical application of probiotics is broadening as this area continues to be one of the main foci of basic and clinical research in gastroenterology.”

For more information about VSL#3, visit: www.VSL3.com. To learn more about Natren’s Life Start or other products, visit: www.natren.com.