Viral infection, Th2 Shift and Intestinal Permeability (Study Compilation)

Here is a small compilation about intestinal permeability (IP). In fact I will knock you down with this study right at the beginning. It seems that viruses like HIV (so maybe XMRV too) induce IP and antiviral therapy cures it:

PMID: 18936106
CONCLUSIONS: Suppressive HAART abrogates HIV-induced intestinal barrier defect and villous atrophy. The HIV-induced barrier defect is due to altered tight junction protein composition and elevated epithelial apoptoses. Mucosal cytokines are mediators of the HIV-induced mucosal barrier defect and villous atrophy.

The following study is from 1994. Can you imagine that? These scientists are probably 20 years ahead of their colleagues. If you tell a doctor about leaky gut he will likely think that you are mental case. The doctors today know nothing. They don't know anything about reactivating viral infections nor do they know anything about leaky gut and the consequences for so many diseases.

Neonatal babies (up to the fourth week of life) seem to have an increased intestinal permeability because the digestive tract still has to develop. These scientists took a look at it and come to the conclusion:

Evidence exists that the increased uptake of intact
food proteins in early infancy could play a role in the development of various
clinical disorders, including food allergy, coeliac disease and pancreatic insufficiency,
but this uptake might also be important for the normal development
of oral tolerance.

IP plays a role in milk allergy.

Intestinal permeability is thought to play a role in
the pathophysiology of cow's milk allergy. Furthermore, it is a common
diseasein early infancy, often the first presentationo f the atopic syndrome. In the first study,(chapter3 .2) we showedt hat intestinal permeability
as measuredb y the SAT, increasesd uring cow's milk challengei n infants
with clinically positive cow's milk challengesc omparedt o children with clinically negativec ow's milk challenge

Then they found out that IP is increased in celiac patients AND to some lower degree in many relatives.
After that they looked at pancreatic insufficiency and found out the following:

We measured intestinal permeability
in rystic fibrosis- and nonrystic fibrosis patients with pancreatic
insufficienry and found that intestinal permeability was increased in both
groups. In rystic fibrosis patients, we found that intestinal permeability did
not changeb y increasingp ancreatice nzFmes upplementationb y 30-50o/ofo r
2 weeks, nor by decreasing the osmolarity of the test solution of the SAT by
75o/oW. e conclude that an increased intestinal permeability in cystic fibrosisis
probably a consequence of pancreatic insufficienry, and is not related to
the dose of pancreatic enzyme supplementation nor the osmolarity of the test
solution. The increase is due to an increased permeability for lactulose which
might point towards a defect in the tight junctions of the villi and/or the

Another study:

A defective skin barrier and increased intestinal permeability appear to facilitate allergen sensitization.

A new study that links intestinal permeability to atopic disease.

The researchers concluded: "Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups."

Next, viral connections:

PMID: 20386714
Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals.

PMID: 19372990
In addition HIV infection of humans and SIV-infection of rhesus macaques are characterized by enteropathy and increased intestinal permeability.

Some not so good news:

PMID: 19732776
CONCLUSIONS: HIV PIs induce ER stress and activate the unfolded protein response in intestinal epithelial cells, thus resulting in disruption of the epithelial barrier integrity.

Is this a direct connection to HHV-6/7?

PMID: 17570213
LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpes virus entry on T cells) is a tumor necrosis factor core family member that regulates T-cell activation and causes experimental inflammatory bowel disease. ... T cell-derived LIGHT activates intestinal epithelial LT beta R to disrupt barrier function. This requires MLCK activation and caveolar endocytosis. These data suggest a novel role for LIGHT in disease pathogenesis and suggest that inhibition of MLCK-dependent caveolar endocytosis may represent an approach to restoring barrier function in inflammatory bowel disease.

Thank you for reading this.


Senior Member
Toxic Mold and Intestinal Permeability

Here are some articles detailing some effects of trichothecenes on intestinal cells. I suspect that the combination with the effects of the virus are particularly problematic.


Yang H, Park SH, Choi HJ, Moon Y. Epithelial cell survival by activating transcription factor 3 (ATF3) in response to chemical ribosome-inactivating stress. Biochem Pharmacol. 2009 Mar 15;77(6):1105-15. PMID: 19101521

Ribotoxic stress responses lead to the expression of genes important for cellular homeostasis by modulating cell survival, proliferation and differentiation.

ATF3 expression was up-regulated by chemical agents causing ribotoxic stress such as deoxynivalenol and anisomycin in different types of intestinal epithelial cells.

Moreover, reduction of ATF3 gene expression promoted ribotoxic stress-triggered programmed cell death, implicating a protective role of ATF3 in epithelial cell survival.


Van De Walle J, Romier B, Larondelle Y, Schneider YJ. Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells. Toxicol Lett. 2008 Apr 1;177(3):205-14. PMID: 18343055

We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion.

Dose-dependent increases in NF-kappaB activity and IL-8 secretion were observed,

Phosphorylation of inhibitor-kappaB (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml.

Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF-kappaB and increased IL-8 secretion.

Synergistic interactions between these stimuli and DON were observed.

These data show that DON induces NF-kappaB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.


Kouadio JH, Dano SD, Moukha S, Mobio TA, Creppy EE. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells. Toxicon. 2007 Mar 1;49(3):306-17. PMID: 17109910.

We studied the interactive effects of either binary or tertiary mixtures of Fusarium mycotoxins, deoxynivalenol (DON), zearalenone (ZEA), and fumonisin B1 (FB1) on the human intestinal cell line, Caco-2,

Because FB1 antagonizes the effects of estrogenic Zearalenone, FB1 was assayed against estradiol.

In NR assay, mixture of FB1 and estradiol and/or ZEA improves Caco-2 cells viability in contrast to individual effects. Mixtures of ZEA or FB1 and DON, display synergistic effects in lipid peroxidation.

Altogether, the data indicate that mixtures of Fusarium toxins are able to induce lipid peroxidation, DNA damage, DNA fragmentation, DNA methylation, and cytotoxicity in Caco-2 cells, and suggest a potential promoter effect in human intestinal cells.


Li M, Cuff CF, Pestka JJ. T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-gamma responses. Toxicol Appl Pharmacol. 2006 Aug 1;214(3):318-25. PMID: 16504231

Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity.

The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection.

As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days.

T-2 suppressed IFN-gamma responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days.

Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-gamma responses.


Sergent T, Parys M, Garsou S, Pussemier L, Schneider YJ, Larondelle Y. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicol Lett. 2006 Jul 1;164(2):167-76. PMID: 16442754.

Epidemiological studies suggest a link between DON and gastrointestinal illness.

We investigated the interaction of DON with Caco-2 cells, a widely used in vitro model of the human intestinal barrier.

These data imply that a chronic exposure to DON contaminated foods may negatively affect human health by altering the intestinal mucosa integrity and by inducing the MAPKs implicated in inflammation.


Kouadio JH, Mobio TA, Baudrimont I, Moukha S, Dano SD, Creppy EE. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2. Toxicology. 2005 Sep 15;213(1-2):56-65. PMID: 16019124

Fusarium toxins such as, deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) have been shown to cause diverse toxic effects in animals and also suspected of disease causation in humans. From the literature and mechanistic point of view, DON binds to the ribosomal peptidyl-transferase and inhibits protein synthesis specifically and DNA synthesis consequently. ZEN known to be genotoxic, binds to 17-beta-estradiol receptors, induces lipid peroxidation, cell death and inhibits protein and DNA synthesis. FB1 disrupts sphingolipid metabolism, induces lipid peroxidation altering the cell membrane and causing cell death.

We intended to compare DON, ZEN and FB1 (1-150 microM) cytotoxic effect and the pathways leading to cell death and related to oxidative stress and macromolecules syntheses in a human intestinal cell line in order to tentatively classify them according to their respective potential toxicity.

The comparison reveals that all three mycotoxins bear, at variable degree, the capability of inducing lipid peroxidation (MDA production) and could be classified above 10 microM in decreasing potency order FB1>DON>ZEN.

This effect seems to be related to their common target that is the mitochondria as revealed by MTT test and seemingly not related to sphingoids accumulation concerning FB1.

DON and ZEN also adversely affect lysosomes in contrast to FB1.

The three mycotoxins inhibit protein synthesis with respective IC50 of 5, 8.8 and 19 microM for DON, FB1 and ZEN confirming that protein synthesis is a specific target of DON.

DNA synthesis is inhibited by DON, ZEN and FB1 with respective IC50 of 1.7, 10 and 20 microM. However at higher concentrations DNA synthesis seems to be restored for FB1 and DON suggesting a promoter activity.

Altogether the potency of the three mycotoxins in macromolecules inhibition is DON>ZEN>FB1 in Caco-2 cells. It appears then that FB1 acts rather through lipid peroxidation while DON affects rather DNA and protein synthesis.
Very interesting. I really hope that zonulininhibitors are a solution to this but I still wonder how a zonulininhibitor will work. If it blocks zonulin the tight junctions won't open and by this, nutrients cannot be absorbed either, can they?