Transcript A Cruise Down the Alimentary Canal

Nutrition and the
Gastrointestinal Ecosystem
Leo Galland M.D.
Foundation for Integrated Medicine
www.mdheal.org
BEYOND DIGESTION
• The gut is a sensory organ. Protozoa know their
environments by ingestion.
• The gut is a neuroendocrine organ. Every CNS
neurotransmitter is present and active here.
• The gut has a brain of its own, an intact and
independent nervous system.
• The gut is the largest organ of immune function
in the body; 70% of our lymphocytes live here.
BEYOND DIGESTION
• The gut contents are an inner world that is
“outside” the cellular body. Its surface is a
frontier of 100 square meters and a thickness
of one cell
• Gut flora are an organ that contains as many
microbial cells as the cellular body has
mammalian cells (100 trillion)
-Over 500 species
-Over 90% are anaerobic
BEYOND DIGESTION
• The normal intestinal microflora constitute
a huge chemical factory that alters our
food and our GI secretions
• The normal intestinal microflora present
our immune systems with a mass of
antigens that are partially absorbed
Three Components of the
GI Ecosystem
• Diet
• Microbial flora
• Mucosa
•
•
•
•
•
Epithelium
Mucus layer
Immune cells
Blood vessels
Nerve endings
Gastric Ecosystem
• Low fasting pH
– Reduces bacterial population
– Denatures protein, initiates protein digestion
– Enhances solubility of Ca, Mg, Fe, Zn…
• Thick coat of protective mucus
• Intermittent exposure to food and oral or
exogenous microbes
• Rapid emptying (60 minutes)
Gastric Acid Production
• Two liters of gastric juice per day
• Fasting HCl secretion is 10% of
maximum, yielding pH 1.0-2.0 and
bacteriostatic barrier
• Food buffers gastric acid despite postprandial HCl secretion. pH of the fed
stomach is typically 3.5 – 4.5
• Ageing slows gastric reacidification but
has little effect on fasting or fed pH
Gastric Ecosystem Disruptors
•
•
•
•
•
H. pylori infection
Acid-lowering drugs
NSAIDs
Malnutrition (B12)
Delayed emptying (gastroparesis)
– Drugs (clonidine)
– Disease (diabetes)
Helicobacter pylori
•
•
•
•
•
Most common chronic bacterial pathogen of humans
Prevalence in adults is approximately 1%/year of life
Infection can be life-long
Lives under the mucous layer, protected from HCl
Pathogenicity is associated with provocation of TH1
cells and gastric mucosal IL-8 secretion and
bacterial synthesis of CagA, a disruptor of
mammalian cell signaling mechanisms
• Raises gastric pH by producing ammonia and by
damaging gastric epithelial cells
• May cause hyperacidity by destroying somatostatinproducing antral mucosal cells
H. Pylori Effects: GI
•
•
•
•
•
•
•
Atrophic and autoimmune gastritis
Erosive gastritis and NSAID gastropathy
Hypertrophic gastritis
Duodenal ulcer disease
Gastric carcinoma
Gastric lymphoma
Functional dyspepsia/gastroparesis
H. Pylori Associations: Systemic
•
•
•
•
•
•
Coronary heart disease
Stroke
Rosacea
Raynaud’s syndrome
Sjogren’s syndrome
Open angle glaucoma (Kountouras et al. Arch Int Med 2002;
162: 1237-1244.)
• Food allergies
• Vitamin B12 deficiency
Atrophic Gastritis
• Atrophic gastritis is non-erosive inflammation
associated with loss of secretory function
• Usually asymptomatic but may produce
–
–
–
–
Dyspepsia
Abdominal pain
Bloating
Nausea/vomiting
• May co-exist with erosive peptic disease
• Allows gastric bacterial overgrowth
• Increases susceptibility to pathogens in food
Achlorhydria and Atrophic Gastritis
• Achlorhydria affects 15% of people >
25, 30% of people > 65
• Achlorhydria is a symptom of atrophic
gastritis, not a normal effect of aging
Hurwitz et al, JAMA 1997;278: 659-62.
• Achlorhydria is usually caused by H.
pylori or by the use of acid-lowering
drugs
H. Pylori: After Effects
• Residual gastritis and achlorhydria can
take 2 years or more to resolve.
• HCl supplementation: 2 grams of
Betaine HCl is needed to take 400ml of
gastric juice from neutral to pH 2.0
• B12 repletion improves gastroparesis
Gumurdulu et al J Clin Gastroenterol 2003; 37:230-3.
Food Effects on H. Pylori
• Mastic gum (P lentiscus), used in rice pudding
and for treatment of dyspepsia, kills H. pylori
• Raw garlic and aqueous garlic extract inhibit
growth (thiosulfinate, MIC of 40 mcg/ml)
– Garlic and onion consumption inversely associated
with gastric cancer
• Sulforaphane (cabbage and broccoli) has MIC of
<4 mcg/ml
– Cabbage juice and broccoli sprouts have been used
to treat PUD
Acid Lowering Drugs
• May increase development of atrophic
gastritis in H. pylori-infected individuals
• Allow gastric bacterial/yeast overgrowth
and post-prandial intra-gastric production
of ethanol and nitrosamines
• May impair absorption of vitamin B12, folic
acid, carotene, minerals and medication
Esophageal Reflux
• Results from reflex relaxation of the LES in response to
gastric vagal mechanoreceptors (programmed in
brainstem, unrelated to swallowing or gastric pH). Postprandial gastric distension is a key trigger.
• PPI’s and H-2 blockers convert acid reflux into non-acid
reflux. Pepsin and bile present in gastric juice may still
act as esophageal irritants.
• Intra-gastric calcium increases LES tone, independent of
antacid effects, and may be a more physiologic
treatment, along with consumption of small meals eaten
slowly in a relaxed fashion to decrease gastric distention.
• Red-pepper powder 800 mg t.i.d. relieves symptoms
Bortolotti et al, NEJM 2002; 346: 947-8.
Colonic Ecosystem
• Relatively slow motility (about 48 hours)
• Immense bacterial count (100 trillion
organisms, weight of about 3 lbs)
• pH of 6-8, determined by SCFAs vs NH4
• Water gradient caused by re-absorption of
fluid
• Ileo-cecal backflow may damage the
terminal ileum
Colonic Ecosystem Disruptors
•
•
•
•
•
Antibiotics
Infection
Unabsorbed bile acids
Bacterial putrefaction
Altered motility
– Disease
– Drugs, supplements
– Stress, lifestyle
GI MICROFLORA
AND COLON CANCER
• Large bowel cancer is associated with
high fat, high protein, low fiber diets
• This effect is in part mediated by bacterial
enzymes induced by the nature of the diet,
the substrates supplied for these enzymes
and the carcinogenic products of enzyme
activation
BILIARY STEROID METABOLISM
BY GI MICROFLORA
• chenodeoxycholate
lithocholate
• cholic acid
deoxycholic(DCA)
-DCA in feces correlates with colon
cancer incidence
-DCA may
20-CH3-cholanthrene
• Deconjugation of bile salts
GI MICROFLORA
AND COLON CANCER
• Incidence proportional to DCA excretion
– inversely proportional to Lactobacillus
concentration
• Vegetarians have less cancer and lower
bacterial enzymes in stool: Betaglucuronidase, nitro-reductase, 7-alphadehydroxylase;
– Lactobacilli lower these when fed to
omnivores and prevent colon cancer in
rats given dimethylhydrazine
GI MICROFLORA
AND COLON CANCER
(continued)
• High meat diets increase indole and skatole in
stool: inducing bacterial tryptophanase
• Human fecal mutagen (FCM), a vinyl ether of
propanediol, is associated with a Western diet.
Requires bile and low oxygen. Produced by 5
Bacteroides spp
• High protein diets
high GI ammonia and
high fecal pH. This increases fecal LCFA and
bile acid solubility
GI MICROFLORA
AND COLON CANCER
(continued)
• High CHO/fiber diets
high SCFA
and low fecal pH. This decreases
fecal LCFA and bile acid solubility
Dietary Ca also renders LCFA
insoluble
DIETARY PREVENTION OF
COLONIC DYSBIOSIS
•
•
•
•
•
Plant-based, high fiber diet
Fermented foods, Lactobacilli
Crucifers, flavonoid-rich vegetables & fruits
Vegetable cellulose, an insoluble fiber
Colostrum, a source of lactoferrins
-Lactoferrins bind iron, inhibiting the growth of all
bacterial species except lactic acid producers
Probiotics
• Lactic acid producers: Lactobacilli
(acidophilus, plantarum, casei, salivarius,
sporogenes), Bifidobacteria, Streptococci
• Non-pathogenic E. coli
• Soil-derived organisms: Bacilli
(laterosporus, subtilis)
• Saccharomyces boulardii (yeast against
yeast)
Prebiotics
• Foods that support the growth of
probiotics: bran, psyllium, resistant starch
(high amylose), oligofructose (FOS), inulin,
germinated barley foodstuff (GBF)
• FOS is found in onions, garlic, rye,
blueberries, bananas, chicory. Dietary
intake averages 2-8 gm/day.
• Inulins are derived from chicory and
artichoke
GBF and Ulcerative Colitis
• GBF 20-30 gm/day helps to induce and
maintain remission in patients with
ulcerative colitis.
• Mechanism: Increased colonic butyrate
production decreases NFkB activation.
Hanai et al. Int J Mol Med. 2004 May;13(5):643-7.
Kanauchi et al. J Gastroenterol. 2003;38:134-41.
Kanauchi et al, Int J Mol Med. 2003;12:701-4
Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14:67-72.
.
E.COLI AND ULCERATIVE
COLITIS
• E. coli in colonic crypts of UC patients shows
abnormal adherence
Burke, Axon J Clin Path 40: 782-786 (1987)
• After inducing remission with gentamycin and
prednisone, Nissle 917 strain E. coli were as
effective as mesalamine in maintaining
remission at 12 months
Rembacken et al, Lancet 354: 635-640 (1999)
BENEFITS OF
BACILLUS LATEROSPORUS
• Laterosporamine: antibiotic
–Suppress auto-antibody formation
–Suppress murine lupus nephritis
• Spergualin: anti-tumor, antibiotic
BENEFITS OF
SACCHAROMYCES BOULARDII
• Stimulates production of sIgA
• Protects against antibiotic and
traveler’s diarrhea
• Helps reverse C difficile colitis
• Improves acute diarrheal disease in
children
LACTOBACILLI:
BENEFICIAL EFFECTS
• Produce organic acids: lower bowel pH
• Produce H202
• Antagonize enteropathogenic E. Coli, Salmonella,
Staphylococci, Candida albicans, and Clostridia spp
• Degrade N-nitrosamines
• Anti-tumor glycopeptides (L. bulgaricus)
• Stimulate balanced immune responses
• Decrease rate of post-op infection (L plantarum)
Lactobacilli for Prevention of
Food Allergy in Infants
• DBPCT: Lactobaciilus GG given to high risk
mothers during last 2 weeks of pregnancy and
for 6 months after birth to their offspring
• Atopic eczema at 2 years
– Controls: 31/68 (46%)
– Lactobacillus 15/64 (23%), RR=0,51
Kalliomaki et al, Lancet 357: 1076-79 (2001)
Lactobacilli for Managing
Food Allergy
• Infants with atopic eczema and cow’s milk
allergy fed hydrolyzed whey formula with or
without Lactobacillus GG
-Clinical improvement associated with 95%
decline in fecal TNF-alpha in the Lactobacillus
group, signifying reduced GI inflammation
Majamaa, Isolauri, J All Clin Immunol 1997
Small Intestinal Ecosystem
• Great length (25 ft) and immense surface
area (= a doubles tennis court)
• Enzyme/bile acid gradient
• Bacterial gradient
• Intense immune activity
– Intraepithelial lymphocytes (CD8)
– Peyer’s patch lymphocytes (CD4)
Enteric Ecosystem Disruptors
•
•
•
•
•
•
Loss of beneficial flora (Lactobacilli)
Bacterial overgrowth/fermentation
Exuberant immune responses
Mucosal hyperpermeability
Altered motility
Malnutrition (systemic and local:
parenteral feeding, low fiber diets)
• Infection
CAUSES OF UPPER GI
BACTERIAL OVERGROWTH
• Achlorhydria/hypochlorhydria
• Surgical
resection/blind loops
• Stasis from
abnormal motility
• Strictures
•
•
•
•
Fistulas
Diverticulosis
Immune deficiency
Intestinal
giardiasis
• Tropical sprue
• Malnutrition
EFFECTS OF UPPER GI
BACTERIAL OVERGROWTH
• Carbohydrate/fiber intolerance,
bloating, altered bowel habit, fatigue
• Vitamin B12 deficiency
• Bile salt dehydroxylation
– Impairs formation of micelles
• Bile salt deconjugation
– Increases colonic water secretion
– Inhibit monosacchardide transport
EFFECTS OF UPPER GI
BACTERIAL OVERGROWTH
(continued)
• Inhibition of folate conjugases
• Increased fecal nitrogen,
hypoalbumenia
• Bacterial degradation of CHO
• Villi: blunted and broadened
• Lamina propria: increased
mononunuclear cells
EFFECTS OF UPPER GI
BACTERIAL OVERGROWTH
(continued)
• Mucosal damage by bacterial
enzymes
– Loss of brush border
• Endotoxemia/antigenemia
• Liver damage
• Joint disease
BREATH TESTING FOR
BACTERIAL OVERGROWTH
• FALSE POSITIVES
– Smoking, sleeping, eating
– Soluble fiber/FOS
– Rapid intestinal transit
• FALSE NEGATIVES
– Colonic hyperacidity (low stool pH)
– Absence of appropriate flora
– Delayed gastric emptying
– Antibiotics
BACTERIAL OVERGROWTH IS
MORE COMMON THAN SUSPECTED
• 202 patients with IBS underwent hydrogen
breath testing
• 157 (78%) had SBBO and were treated
with antibiotics
• 25/47 patients had normal breath tests at
follow-up
• Diarrhea and abdominal pain were
significantly improved by treatment
SBBO AND IBS:
CONCLUSIONS
Elimination of SBBO eliminated IBS in 12/25
of patients:
48 % of patients with IBS and abnormal
breath tests who responded to antibiotics
with normal breath tests no longer met
Rome criteria for IBS
Pimentel M et al, AM J Gastroenterol 2000
Small Bowel Bacterial Overgrowth
and Fibromyalgia (FMS)
• Lactulose breath tests: 153 patients (42
FMS, 111 IBS) and 15 healthy controls
• All 42 FMS and 93 (84%) of IBS had an
abnormal LBT, but only 3 (20%) of
controls.
• Breath hydrogen correlated with the
degree of pain in FMS.
Pimentel, Ann Rheum Dis 2004; 63: 450-2
MANAGEMENT OF UGI BACTERIAL
OVERGROWTH INVOLVES DIET,
ANTIBIOTICS
• Low fermentation diet
-restrict sugar, starch, soluble fiber
• Antimicrobials (in select cases):
– Metronidazole (anaerobes)
– Tetracyclines (anaerobes)
– Ciprofloxacin (aerobes)
– Bismuth
– Bentonite
Low Fermentation Diet
• Basic diet: no wheat, sucrose, lactose
• Additional restrictions
-no glutinous grains
-no cereal grains, potatoes
-restrict fruits, juices, honey
-avoid legumes
-cook all vegetables
UGI Flora, Molecular Mimicry
and Exuberant Enteric Immunity
• Cross-reactivity to bacterial antigens
leads to immune-mediated damage
• Antibodies against microbes bind to
cells carrying HLA antigens
• Inflammation from complement or
cytokine cascades, T cell activation
INTESTINAL INFLAMMATION AND
SPONDYLOARTHOPATHIES
• Arthritis is a frequent complication of
IBD
• Sub-clinical ileitis occurs in many pts
with ankylosing spondylitis (AS);
associated with increase sIgA
• Bowel infections often precede reactive
arthritis
• Silent carriage of Salmonella can
precipitate reactive arthritis
KLEBSIELLA AND ANKYLOSING
SPONDYLITIS (AS)
THE EBRINGER RESEARCH
• 96% of AS patients have HLA-B27,
cross-reacts with Klebsiella antigen
• Many AS patients grow Klebsiella on
stool culture
• AS pts have higher serum IgA against
Klebsiella than controls
Nutritional Therapy for
Ankylosing Spondylitis
• A diet free of grains and disaccharides
reduced levels of Klebsiella in stool,
lowered the level of anti-Klebsiella IgA and
improved the symptoms of patients with
AS
Ebringer, Balliere’s Clin Rheumatol, 1989
CELIAC DISEASE (CD) IS
PREVALENT AND PROTEAN
• Overall prevalence of celiac disease (CD) in US
was 1:133. Among patients with chronic GI
symptoms it was 1:57.
Fasano et al, Arch Int Med 2003; 163: 286-92.
• Commonest symptoms of CD patients in the US
are fatigue (82%), abdominal pain (73%),
bloating (72%) and anemia (63%). Half deny
diarrhea or weight loss and 62% are normal- or
overweight.
Zipser et al.Dig Dis Sci 2003; 48: 761-4.
THE DIAGNOSIS OF CD
IS USUALLY MISSED
• Almost 1% of children in Finland have CD (biopsy
proven), but only 25% of these had been evaluated for
CD based on clinical presentation.
Maki et al, NEJM 2003; 348: 2517-24.
• IgG and IgA gliadin antibodies occur in 2% of Italian
school children
Catassi et al, Lancet 343: 200-203 (1994)
• Reliance on a single serological marker (gliadin-IgA,
anti-TGA, anti-EMA) underestimates CD prevalence
Shamir et al, Am J Gastroenterol 2002; 97: 2589-94.
CD Is Associated with
Neuropsychiatric Disorders
• Gliadin or endomysial antibodies and villous atrophy
were found in 16-19% of Swedish children with Down
syndrome, none of whom had clinical CD.
Carlsson et al, Pediatrics 1998; 101: 272-5.
• Gliadin antibodies were found in 30/53 patients with
neurological disease of unknown cause (73% had
abnormal small bowel biopsies)
Hadjivassiliou et al, Lancet 1996; 347: 369-71
• CD is associated with subclinical thyroid disease, panic
and major depressive disorders
Carta et al. J Psychosom Res 2002; 53:789-93
Pathogenesis of Celiac Disease
• Genetic predisposition: HLA DQ2
• Gliadin peptides bind to tissue transglutaminase
(TGA), the CD auto-antigen, activating cytotoxic
(CD8+)T cells of the adaptive immune system
• Gliadin peptides also induce macrophages of
the innate immune system to produce IL-15,
which is essential for priming the adaptive
immune response.
Maiuri et al, Lancet 2003; 362: 30-37.
Gliadin may stimulate innate GI immunity
Gut Flora and Expression of Celiac
Disease Phenotype
• Bacterial prolyl endopeptidase deaminates the critical
gliadin peptides, preventing TGA binding
Shan L, et al Science 2002;297:2275-9
• C albicans hyphal wall protein-1 binds to TGA, permitting
C albicans mucosal adherence. TGA-yeast bonding may
stimulate formation of anti-TGA and anti-endomysial
antibodies. C albicans may cause symptoms of celiac
disease in patients not responding to a gluten-free diet.
Anti-yeast treatment might relieve these symptoms.
Nieuwenhuizen, et al, Lancet 2003;361:2152-4.
EPITHELIAL PERMEABILITY
REGULATES TRANSPORT OF WATER,
SOLUTES AND PARTICULATE MATTER
“The intestinal epithelium is the site of vectorial
transport…between the intestinal lumen and the
circulation. The net effect of transport is
regulated by the tightness (or leakiness) of the
barrier and vice versa. Both transport and barrier
functions are physiologically regulated, and both
can be dramatically altered under disease
conditions.”
Ann NY Acad Sci 915 (2000), p xi
MECHANISMS WHICH SUPPORT
NORMAL INTESTINAL
PERMEABILITY
•
•
•
•
•
Intestinal mucus
Secretory IgA
Mucosal epithelium
Intramural macrophages
Intramural lymphocytes
– intra-epithelial
– in Peyer’s patches
TWO TYPES OF
EPITHELIAL PERMEABILITY
• Trans-Cellular
• Para-Cellular
TRANS-CELLULAR
PERMEABILITY
• The principal route for
the absorption of
solutes, fluid and
macromolecules
PARA-CELLULAR PERMEABILITY IS
LIMITED BY CELL ADHERANCE
MOLECULES (CAMs)
• Tight junctions contain claudins
• Adherens junctions and
desmosomes contain cadherins
• Contraction of the cytoskeleton
opens junctions (glucose
absorption is a stimulus)
CAUSES OF INCREASED
PARA-CELLULAR
PERMEABILITY
• Infectious agents
–Parasites
–Bacteria
–Viruses
–Yeasts
Continued
CAUSES OF INCREASED
PARA-CELLULAR PERMEABILITY
• Enterotoxins
– Ethanol
– NSAIDs*
– Cytotoxic drugs
• Dysoxia
– Ischemia
– Reactive oxygen species
PSYCHOLOGICAL STRESS CAN
INCREASE GUT PERMEABILITY
THROUGH A CHOLINERGIC MECHANISM
• Rats: cold stress increases para-cellular
permeability.
-This effect is greater when cholinesterase activity is weak
-The effect is blocked by atropine
-It may depend upon vagal activation of
mast cells
• Similar effects occur in humans
DIET ALTERS INTESTINAL
PERMEABILITY
• Fasting:
– Controls: Increased I.P.
– R.A.: Decreases I.P.
• Mucosal Inflammation increases I.P.
– Food allergy
– “Idiopathic”(celiac disease)
Continued
• Increased I.P. induced by:
–Low-fiber diets
–Carrageenan
–Pectin/guar gum
–Castor oil
–Alcohol
–Allergens
Continued
INTESTINAL PERMEABILITY IS MEASURED BY
PROBES ABSORBED AND EXCRETED
UNCHANGED BY THE KIDNEYS
• Probes used for small bowel permeability
include Cr51-EDTA, PEGs and the ratio of
lactulose to mannitol.
• Colonic permeability can only be
measured if the probe is administered by
enema.
INCREASED INTESTINAL
PERMEABILITY (LEAKY GUT) IS
NOT A DISEASE OR SYNDROME
• It contributes to the pathophysiology of
many different diseases.
• Improvement of the related disease
usually improves the leaky gut.
• Decreased intestinal permeability may
improve the associated disease.
LEAKY GUT SYNDROMES
• Enteritis, colitis
Infectious/inflammatory
• Arthritis, chronic
inflammatory
• Food allergic
disorders
• AIDS
• CFIDS
• MCS
• Chronic pancreatic
disease
• Chronic noninfectious hepatitis
• Acne
• Psoriasis
Intestinal Permeability and
Food Allergy
• Increased baseline
permeability
• Marked increase after
challenge
• Increase blocked by sodium
cromoglycate
ABNORMAL INTESTINAL
PERMEABILITY IN
FOOD ALLERGY
• 42% of children with eczema had reduced
jejunal villus:crypt ratios (malabsorption)
• Increased PEG-4K absorption (leakiness)
• Increased PEG absorption blocked by
cromolyn pre-treatment
• Increased fasting lactulose absorption in
adults with food allergy (eczema, hives);
further increase with offending food blocked
by cromolyn 300mg
• “Evaluation of I.P… provides an
effective means of diagnosing food
allergy”
Barau E and Dupont C, Modifications
of Intestinal Permeability during Food
Provocation Procedures in Pediatric
Irritable Bowel Syndrome,
J Pediatr Gastroenterol Nutr, 11:72-77,
1990
Continued
INTESTINAL PERMEABILITY
AND CROHN’S DISEASE
• Patients have increased I.P.
• First degree relatives have high I.P.
and excessive increase in I.P. when
exposed to aspirin
• Patients have abnormal reactivity of
mucosal lymphocytes to normal gut
flora and Candida antigens
INTESTINAL PERMEABILITY
AND CROHN’S DISEASE
• For patients in remission, the
rate of relapse correlates with
I.P. measured prospectively
Wyatt J et al, Intestinal Permeability and the
Prediction of Relapse in Crohn’s Disease,
Lancet 341:1437-1439, 1993
HYPER-PERMEABILITY
IN RHEUMATOID ARTHRITIS
• NSAIDs increase intestinal
permeability
• Increased I.P. allows
sensitization to gut flora
• Bacterial sensitization causes
enteritis and formation of
circulating immune
complexes
HYPER-PERMEABILITY
IN RHEUMATOID ARTHRITIS
(continued)
• I.P. is further increased
• Systemic inflammation
exacerbates
• Metronidazole and minocycline
break the cycle
PROTEUS AND RHEUMATOID
ARTHRITIS (RA)
• Frequency of HLA-DR4 in RA patients: 50
to 75%. Those without HLA-DR4 usually
have DR-4 + mothers.
– Controls: 20% HLA-DR4 positive
• RA patients often have elevated serum
IgG titers to Proteus spp that cross-react
with HLA-DR4
Proteus, RA and Diet
• RA patients in England, Spain and Norway have
higher anti-Proteus IgG than controls
• Anti-Proteus IgG correlates with disease activity
and C-reactive protein levels
• Fasting, followed by a one year gluten-free
vegan diet improves symptoms and indices of
disease activity, only in patients whose Proteus
antibodies decrease and who show a change in
fecal bacterial fatty acid profiles. E coli
antibodies are not affected
TREATMENT OF
HYPER-PERMEABILITY
• Avoid enterotoxins
• Treat intestinal infection/bacterial
overgrowth with antimicrobials
• Diet: high nutrient density
– non-irritating
– allergen-free
HELPING TO REPAIR THE
DAMAGED INTESTINE
• Glutamine
• Essential fatty acids
• Antioxidants
– Glutathione
– Bioflavonoids
– Vitamin E
– Gamma-oryzanol
• Epidermal growth factor
• Colostrum