Second
Annual Symposium on Probiotics, Prebiotics and Enzymes: Clinical
Applications in Human Health
Hosted by University of Nevada School of Medicine, November 14-15,
2008
– Las Vegas, Nevada
On November 14 and 15, the University of Nevada School of Medicine
hosted the "Second Annual Symposium on Probiotics, Prebiotics,
and Enzymes: Clinical Applications in Human Health." The conference
was organized and sponsored by Klaire Labs, a division of ProThera
Inc. 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. 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 Saccharomyces boulardii's beneficial
effect in C. difficile-associated disease is due in part to prevention
of inhibitory kBa degradation. This effect prevents C. difficile's
toxin A from activating nuclear factor- kB (NF-kB), which is how
toxin A causes colonocyte death. 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-k induced damage and apoptosis.
On day two, 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. 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.
Martin Katzman and Richard Lord concluded the first day of the symposium
with their thought-provoking lectures. 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. 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, on day two
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 protect them 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. 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's 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.
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 emeritus of medicine at Stanford University
School of Medicine and director of the Stanford Celiac Sprue 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, professor emeritus 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 US 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 in St. Louis, 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 Kalliomäki's group in Finland
has published data showing that alterations in gut microbiota during
early childhood predict overweight and obesity in later life. These
alterations consist of reduced populations of bifidobacteria and
increased numbers of Staphylococcus aureus.
Morton expounded on the exciting results of a study he recently
concluded in which L. acidophilus was administered to patients following
Roux-en-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. Morton plans a large multicenter trial to follow
up on this potentially highly important observation.
The 2008 Probiotic Symposium is available on CD and may be ordered
at www.probioticsymposium.com or by calling 888-488-2488. The third
annual Probiotic Symposium is planned for the fall of 2009. Klaire
Labs will also organize and fund this symposium, which will delve
into the role of probiotics, prebiotics, and enzymes in the management
of pathogenic gastrointestinal biofilm and modulation of immune
function.
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