The document discusses the relationship between ankylosing spondylitis and gut health. It notes that subclinical gut inflammation is present in many spondyloarthropathy patients. Two types of gut inflammation are described - acute and chronic. The chronic type resembles Crohn's disease. Increased intestinal permeability is a key mechanism in spondyloarthropathis. Tight junctions regulate permeability and zonulin modulates this. The document discusses optimizing gut microbiota and permeability through probiotics, prebiotics, diet and supplements to help treat spondyloarthropathis through a gut-focused approach.
2. SPONDYLOARTHROPATHIES
The spondyloarthropathy family consists of the
following entities:
Ankylosing spondylitis
Undifferentiated spondyloarthritis
Reactive arthritis
Psoriatic arthritis
Spondyloarthritis associated with IBD
Juvenile onset spondyloarthritis
3. ANKYLOSING SPONDYLITIS AND
GUT
Subclinical gut inflammation has been described
in up to two-thirds of patients with
spondyloarthropathies
Two histologic types of gut inflammation in
patients with SpA can be distinguished: acute
and chronic inflammation
4. ANKYLOSING SPONDYLITIS AND
GUT
The acute type mimics the acute
bacterial enterocolitis and is mainly
seen in patients with reactive
arthritis:
The mucosal architecture is well
preserved
There is a polymorphonuclear
infiltration of the ileal villi and
crypts
There is an increased number of
inflammatory cells
(granulocytes, lymphocytes and
plasma cells) in the lamina propria
5. ANKYLOSING SPONDYLITIS AND
GUT
The chronic type is often indistinguishable
from Crohn’s disease (CD):
The mucosal architecture is clearly
disturbed
The villi are irregular, blunted and fused
The crypts are distorted
The lamina propria is edematous and
infiltrated by mononuclear cells
In some cases aphthoid ulcers and
sarcoid-like granulomas are present
Chronic lesions are more present in
undifferentiated SpA and AS.
6. ANKYLOSING SPONDYLITIS AND
GUT
Increased intestinal permeability or
leaky gut syndrome is a key
mechanism contributing to the
development and chronic course of
ankylosing spondylitis and other
autoimmune diseases and
inflammatory arthritis.
The leaky gut allows substances
such as toxins, microbial antigens,
undigested food, waste, or larger
than normal macromolecules to
leak through an abnormally
permeable gut wall and trigger
cascades of inflammatory
reactions.
Tight junctions (TJs) represent the
major barrier within the pathway
between intestinal epithelial cells
that line the digestion tract
7. ANKYLOSING SPONDYLITIS AND
GUT
Zonulin is a protein regulating
intestinal permeability via
modulation of tight junction
Small intestines exposed to
enteric bacteria secrete zonulin
This secretion occurs only on
the luminal aspect of the
bacteria-exposed small
intestinal mucosa and is
followed by an increase in
intestinal permeability
8. ANKYLOSING SPONDYLITIS AND
GUT
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with ankylosing spondylitis and their healthy relatives. Br J
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Bowel permeability and CD45RO expression on circulating CD20+
B cells in patients with ankylosing spondylitis and their relatives. J
Rheumatol. 1999 Jan;26(1):128-35.
9. ANKYLOSING SPONDYLITIS AND
GUT MICROBIOTA
Gut microbiota consists of a
complex of microorganism
species that live in the digestive
tract
The human body carries about
100 trillion microorganisms in
its intestines, a number ten
times greater than the total
number of human cells in the
body
The metabolic activities
performed by these bacteria
resemble those of an
organ, leading some to liken
gut bacteria to a "forgotten"
organ
10. ANKYLOSING SPONDYLITIS AND
GUT MICROBIOTA
Gut microbiota primary
benefits the host by
generating energy from the
fermentation of undigested
carbohydrates and the
subsequent absorption of
short chain fatty acids.
The most important of these
are butyrates, metabolized
by the colonic epithelium
and normalizing intestinal
permeability.
12. ANKYLOSING SPONDYLITIS AND
GUT MICROBIOTA
HLA B27 influences the
composition of the body’s
endogenous flora and the ‘B27-
shaped flora’ predisposes to
ankylosing spondylitis
HLA-B27 transgenic mice do
not develop spondylitis-like
lesions in germ-free enviroment
Antibiotic therapy prevents
spondylitis and colitis in HLA-
B27 transgenic rats
THE HLA-B27 CONNECTION
13. ANKYLOSING SPONDYLITIS
THERAPEUTIC GOALS
NORMALIZATION OF INTESTINAL PERMEABILITY
OPTIMIZATION OF GUT MICROFLORA
OPTIMIZATION OF TOXIN REMOVAL
REDUCTION OF LOCAL/MUCOSAL
INFLAMMATION
REDUCTION OF SYSTEMIC INFLAMMATORY
RESPONSES AND PREVENTION OF ANKYLOSIS
14. NORMALIZATION OF INTESTINAL
PERMEABILITY
BUTYRATE
Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate
enhances the intestinal barrier by facilitating tight
junction assembly via activation of AMP-activated
protein kinase in Caco-2 cell monolayers. J Nutr. 2009
Sep;139(9):1619-25.
L-GLUTAMINE
dos Santos Rd, Viana ML, Generoso SV, Arantes
RE, Davisson Correia MI, Cardoso VN. Glutamine
supplementation decreases intestinal permeability and
preserves gut mucosa integrity in an experimental
mouse model. JPEN J Parenter Enteral Nutr. 2010 Jul-
Aug;34(4):408-13.
BERBERINE
Gu L, Li N, Gong J, Li Q, Zhu W, Li J. Berberine
ameliorates intestinal epithelial tight-junction damage
and down-regulates myosin light chain kinase pathways
in a mouse model of endotoxinemia. J Infect Dis. 2011
Jun 1;203(11):1602-12
15. OPTIMIZATION OF GUT
MICROBIOTA
PROBIOTICS
live microorganisms which
beneficially improve intestinal
microbial balance
PREBIOTICS
non-digestible polysaccharides that
stimulate the growth and/or activity
of ‘good’ bacteria in the digestive
system
SYNBIOTICS
nutritional supplements combining
probiotics and prebiotics
BUTYRATE
DIGESTIVE ENZYMES
16. OPTIMIZATION OF GUT
MICROBIOTA
CLINICAL TRIALS UTILIZING PROBIOTICS IN
ANKYLOSING SPONDYLITIS
limited number of published clinical trials
insufficient number of participants to make any
meaningful conclusions
absence of reliable clinical or/and laboratory markers
to measure the trials outcome
poor clinical design (low dose of probiotics, poor
selection of the probiotic strains)
18. OPTIMIZATION OF GUT
MICROBIOTA
PREBIOTICS
no published clinical trials
experimental data utilizing beta-glucan and mannan-
oligosaccharides based prebiotics demonstrated
negative effect in animals with experimental colitis
and Crohn’s disease
19. OPTIMIZATION OF GUT
MICROBIOTA
DIETARY MODIFICATIONS
Generic dietary approach (Mediterranean diet, anti-
inflammatory diet, vegan diet etc) has low success rate
Individualized elimination diet
Based on our experience, we do see the best correlation
with IgG4-based food intolerance testing system
The IgG4-based food intolerance testing is performed in
IFSMED lab
The benefits of elimination diet are typically observed in 6-
8 weeks
20. OPTIMIZATION OF GUT
MICROBIOTA
DIGESTIVE ENZYMES
enzymes of animal
origin (pancreatic
enzymes/pancreatin)
plant-based enzymes
medicinal
mushrooms/medicinal
molds-based enzymes
