intestinal permeabiltiy as a precursor of inflamatory gut diseases

[Guest guest]

http://ajpgi.physiology.org/cgi/content/full/276/4/G951

ABSTRACT

The BB rat spontaneously develops autoimmune diabetes. Feeding these

animals a hydrolyzed casein diet significantly reduces the incidence

of this disease, suggesting that a dietary antigen is involved in the

pathogenesis of this disease. In other syndromes associated with

luminal antigens, including celiac and Crohn's disease, increased

intestinal permeability has been suggested to play an etiological

role. Therefore, the objective of this study was to evaluate whether

increased permeability was also present in BB rats before disease

development. By measuring gastrointestinal permeability, in animals

on a regular or hydrolyzed casein diet, we were able to demonstrate

that increased gastric and small intestinal permeability appeared

before the development of both insulitis and clinical diabetes.

Although hydrolysis of dietary protein significantly reduced the

incidence of diabetes, it did not alter the small intestinal

permeability abnormality, suggesting that this is an early event.

Increased permeability appears to have an early role in the genesis

of several immunological diseases and may represent a common event in

these diseases.

INTRODUCTION

THERE ARE SEVERAL inflammatory diseases involving the

gastrointestinal tract in which abnormal paracellular permeability

defects appear to play an important role. In both celiac and Crohn's

disease, an interaction between the host immune system and a luminal

constituent is hypothesized as an initiating event. In the former,

there is good evidence that the luminal constituent is a gluten

fraction, whereas for the latter no clear candidate has been

identified. However, both diseases share an important feature.

Increased intestinal permeability appears to precede the development

of both syndromes. In a dog model of celiac disease, increased

permeability is clearly present before the onset of disease (8, 9)

and a similar pattern has been reported in humans (2).

For Crohn's disease, the data are less clear. However, bypassing the

epithelial barrier and injecting sterile extracts of luminal bacteria

into the intestinal wall of the rat initiates a disease similar to

Crohn's (24). In humans, several studies have now demonstrated that

individuals at high risk of developing Crohn's disease contain a

subgroup that either has increased baseline permeability (12, 13, 23)

or an exaggerated increase in permeability in response to damaging

agents (11). These data support the hypothesis that certain

inflammatory diseases require several preexisting conditions. The

first is a genetic susceptibility for the host immune system to

recognize, and potentially misinterpret, an environmental antigen

presented within the gastrointestinal tract. Second, the host must be

exposed to the antigen or hapten. For instance, in the case of celiac

disease in the Irish Setter model, preventing exposure to dietary

gluten completely prevents disease expression. Finally, the antigen

must be presented to the gastrointestinal mucosal immune system. In

all cases, increased permeability appears to precede disease and

suggests an abnormality in antigen delivery in the development of the

clinical syndrome.

Other diseases share some of these features. In the BB rat,

autoimmune diabetes develops spontaneously and is accompanied by

evidence of insulitis and other autoimmune features. There are data

in this model that dietary antigens may also play a role in disease

initiation. Feeding these animals a hydrolyzed casein diet reduces

the incidence and delays the onset of disease (20). A potential

explanation for these findings would be the removal of a protein

important in disease initiation.

Therefore, this study was designed to evaluate two questions. First,

do BB rats have abnormal gastrointestinal permeability before disease

development? Second, if abnormal permeability is present, does it

depend on the presence of intact dietary protein? Hydrolysis of

dietary protein might be beneficial in these animals, either due to

removal of an antigen important for disease initiation or of a

protein capable of inducing gastrointestinal damage

[Guest guest]

basically there are two issues, fermenting gut flora making for a

leaky gut

and undigested antigens (various undenatured milk protiens) from milk

getting across the leaky gut

now heres the kicker and has really only come out in recent research

these antigens getting into the gut mucosa and gut wall create an

ACCELERATING inflamatory response

so i thought that tied in a bit with the yogurt thing, the need to

reduce the lactose feeding fermentation

but also the need to denature milk protiens that might be interpreted

as antigens if they get into the intestine wall

i think homogenised cows milk is particularly bad for permitting

undigested milk antigens to get into the gut wall because the antigens

are driven into the newly made small fat globules and protected from

digestion

in terms of the research, the inflamation excited by the antigens goes

on to destroy the insulin islets in the pancreas, vastly made worse by

the hep b vaccination imo

there is a rough edge here and that is the body needs some of the milk

proteins, especially cysteine and some of the branched chain amino acids

if you don't have enough of these then you tend to develop oxalate

issues

i don't feel that yogurts have enough of these needed protiens left to

suppy sufficent for the bodies needs

but these are also fermenting protiens so catch 22

> >

> > http://ajpgi.physiology.org/cgi/content/full/276/4/G951

> >

> > ABSTRACT

> >

> >

> ,

> For the benefit of those who cannot easily interpret the abstract

could you sumarize the

> implication of the research results and how SCD would be impacted by

this.

>

> Thanks,

>

> Carol F.

>