Transcript Alternative Therapies for Inflammatory Bowel Disease

Alternative Therapies
for
Inflammatory Bowel Disease
IBD
• Refers to UC and CD
• Affects 1-2 million Americans
• Treated with amino salicylic acids, corticosteroids,
immunomodulators, and antibiotics.
– help maintain remission but also have serious side effects
• Many patients are dissatisfied with the conventional
treatments and therefore seek alternative therapies
– most common forms used are herbal and nutritional
supplements, acupuncture, and diet modification.
– Higher rate of use in IBD patients
– 1/3 of patients seeking gastroenterology care are also receiving
various CAM therapies.
Pathophysiology
• characterized primarily by intestinal wall
inflammation with elevated proinflammatory
cytokines, oxidative stress, and leukocyte
infiltration
• cell-mediated Th1 response
– Includes IL-12, INF-gamma, TNF-α, IL-1, IL-2, IL-6,
and IL-8
• UC is also characterized by a high Th2 response
– elevated levels of IL-5
• The exaggerated T-cell response in both
conditions leads to intestinal damage and
increased permeability
Disruption of Intestinal environment
• Caused by 2 events.
– increased permeability
– disturbance in the intestinal micro flora.
– Either mechanism leads to increased pathogenic
invasion of the intestine.
• Increased mucosal permeability
– Alteration of tight junctions between intestinal
epithelial cells
• allows bacteria to penetrate the mucosal barrier
• Activates intestinal immune response
– The alteration of tight junctions can be mediated by
inflammation, increased TNF-α, and ulcerations
Disruption of Intestinal environment
• disturbance in the intestinal micro flora.
– the normal flora such as bifidobacterium and
lactobacillus are decreased
– pathogenic bacterial are increased.
• stimulates inflammation
– secreting enterotoxins, synthesizing immunosuppressive
proteins, and disrupting epithelial cell metabolism
• The enterotoxins increase intestinal permeability and allow
for the translocation of antigens across the epithelial creating
immune activation
• Since IBD patients are in a chronic state of
inflammation, the micro flora ecosystem is
always altered
Alternative Therapies
• target the disruptions in the intestinal tract that
may predispose individuals to IBD or may
exacerbate the disease
• probiotics, antioxidants, fish oil, curcumin,
glutamine, short chain fatty acids, garlic,
acupuncture and dietary modifications.
• Some are believed to produce the same immune
modulation and suppression as conventional
medications to maintain remission and relapses
control.
Probiotics
• Friendly bacterial in GIT
– Lactobacilli, Streptococci, Bifidobacteria, and certain E. coli subspecies
• Alter intestinal microflora and restore the balance disturbed in IBD
• Potential mechanisms of probiotic action include:
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inhibition of pathogenic microbial growth
modification of intestinal permeability by increasing tight junctions
regulation of intestinal immune response and immune cells
synthesis of antimicrobial metabolites
decomposition of pathogenic antigens in the lumen
• By using a combination of different probiotics such as
Streptococcus, Bifidobacterium and Lactobacillus, studies have
proven their ability to normalize transport function and mucosal
barrier in the intestine as well as the ability to inhibit TNF-α and IFNgamma synthesis
Antioxidants
• protect cells from the damaging effects of free
radicals such as singlet, oxygen, superoxide,
peroxyl radicals, hydroxyl radicals and
peroxynitrite
• Protect by:
– Tissue level: downregulate neutrophil or monocyte
activation which prevents formation of free radicals
– Cellular level: block membrane receptors
– Scavenge free radicals after formation and release
• Vit. C and E, flavonoids and glutathione increase
antioxidant activity
Curcumin
• component of the spice turmeric (Curcuma
longa) that has been proven to have
antioxidant and anti-inflammatory
properties.
• Suppresses proinflammatory cytokines IL12, and TNF-α thru down regulation of
NFқB.
Fish Oil
• Omega 3-fatty acid
• Controls inflammatory response when in
an appropriate balance with omega-6
• competes with arachidonic acid to
decrease prostaglandin, thromboxane and
leukotriene production
Glutamine
• Essential amino acid found in abundance
in the body
• In catabolic states the body’s demand
exceeds its ability to synthesize it
• protects the mucosa and decreases
inflammatory process.
• L-glutamine enemas where shown to be
more beneficial than 5 ASA in rat studies
Short Chain fatty acids
• Primary energy source for colonocytes
• butyrate, acetate, and proprionate
• decrease the synthesis of inflammatory
cytokines, IL-6, IL-8, and TNF-alpha, while
also playing a role in the repair and
regeneration of injured colonic cells
• butyric enemas in UC resulted in
equivalent remission rates as mesalamine
and corticosteroids
Garlic
• Actions in IBD
– suppress IL-8, up-regulate IL-10, inhibit IL-12, and act
as an antibacterial or antifungal agent
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IL-8 attracts neutrophils to site of inflammation
IL-10 is an anti-inflammatory agent
IL-12 promotes INF-gamma production
One study proved that additive therapy of garlic
extract to methylprednisone produced a greater
therapeutic effect than just methylprednisone
alone
Diet modifications
• diet is believed to have the ability to impact the content
and metabolic activity of the human fecal flora
• High sulfur diets
• High protein diets
High Sulfur Diet
• Compromise micro flora in GIT
– Increase synthesis of harmful bacteria
– metabolize by sulfate-reducing bacteria (SRB) in the
colon to sulfide
• Abdominal distention
• Inhibition of butyrate oxidation
• Diet with low intake of sulfur would be beneficial
– Limit intake of preservatives, dried fruits, dehydrated
vegetables, shellfish, white bread, alcoholic
beverages, cow’s milk, cheese eggs, and cruciferous
vegetables
High Protein Diet
• Protein can escape digestion in upper GIT
and reach colon undigested
– Fermented into ammonia, amines, phenols,
sulfide, and indoles by micro flora
• Ammonia alters mucosal cell morphology
and metabolism reducing their life span.
• Phenols and indoles can act as cocarcinogens allowing the development of
bowel cancer.
Conclusion
• Alternative therapies are capable of producing
similar effects as conventional medicines, but
without the serious side effects
• They control the over exaggerated immune
response common in IBD by down regulation of
pro-inflammatory cytokines, restoration of micro
flora balance, and reduction in intestinal
permeability.
• Therefore alternative therapies show promising
use in inflammatory bowel disease either as
mono adjunct therapy.
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