New hypothesis for the rise in IBD in industrialized countries

[Guest guest]

Here's a very interesting new hypothesis for the rise in IBD in

industrializede countries in the 20th century:

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Inflamm Bowel Dis. 2008 Oct 9. [Epub ahead of print]

Bacterial overgrowth and inflammation of small intestine after

carboxymethylcellulose ingestion in genetically susceptible mice.

Swidsinski A, Ung V, Sydora BC, Loening-Baucke V, Doerffel Y,

Verstraelen H, Fedorak RN

Humboldt University, Charité Hospital, Laboratory for Molecular

Genetics, Polymicrobial Infections and Bacterial Biofilms, 10098

Berlin, Germany.

Background: Detergents and emulsifiers added to food may destroy the

mucus barrier, which normally isolates bacteria from the intestinal

wall, and lead to chronic bowel inflammation in susceptible persons.

We investigated the influence of 2% carboxymethylcellulose (CMC) on

the biostructure of the intestinal microbiota in IL-10 gene-deficient

mice.Methods: Twenty to 27-week-old IL-10 gene-deficient mice

received either 2% CMC solution (n = 7) or water (n = 6) orally for 3

weeks. Intestinal bacteria were investigated using fluorescence in

situ hybridization in paraffin-fixed sections of the

intestine.Results: CMC-treated IL-10 gene-deficient mice demonstrated

a massive bacterial overgrowth, distention of spaces between villi,

with bacteria filling these spaces, adherence of bacteria to the

mucosa, and migration of bacteria to the bottom of the crypts of

Lieberkuehn. Leukocytes migrated into the intestinal lumen in 4 of

the 7 CMC mice. The changes were similar to those observed in Crohn's

disease in humans and were absent in control animals.Conclusions: CMC

induces bacterial overgrowth and small bowel inflammation in

susceptible animals. Because of its ubiquity in products and its

unrestricted use in food of the industrial world, CMC is an ideal

suspect to account for the rise of IBD in the 20th century. PMID:

18844217

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This particular mouse model of IBD (IL-10 deficiency) is highly

relevant to ulcerative colitis in humans because IL-10 seems to be

the major susceptibility gene for ulcerative colitis in humans:

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Nat Genet. 2008 Oct 5. [Epub ahead of print]

Sequence variants in IL10, ARPC2 and multiple other loci contribute

to ulcerative colitis susceptibility.

e A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr

G, Domingues FS, Albrecht M, Nothnagel M, Ellinghaus D, Sina C, Onnie

CM, Weersma RK, Stokkers PC, Wijmenga C, Gazouli M, Strachan D,

McArdle WL, Vermeire S, Rutgeerts P, Rosenstiel P, Krawczak M, Vatn

MH; the IBSEN study group, Mathew CG, Schreiber S

Inflammatory bowel disease (IBD) typically manifests as either

ulcerative colitis (UC) or Crohn's disease (CD). Systematic

identification of susceptibility genes for IBD has thus far focused

mainly on CD, and little is known about the genetic architecture of

UC. Here we report a genome-wide association study with 440,794 SNPs

genotyped in 1,167 individuals with UC and 777 healthy controls.

Twenty of the most significantly associated SNPs were tested for

replication in three independent European case-control panels

comprising a total of 1,855 individuals with UC and 3,091 controls.

Among the four consistently replicated markers, SNP rs3024505

immediately flanking the IL10 (interleukin 10) gene on chromosome

1q32.1 showed the most significant association in the combined

verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The

other markers were located in ARPC2 and in the HLA-BTNL2 region.

Association between rs3024505 and CD (1,848 cases, 1,804 controls)

was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an

immunosuppressive cytokine that has long been proposed to influence

IBD pathophysiology. Our findings strongly suggest that defective

IL10 function is central to the pathogenesis of the UC subtype of IBD.

PMID: 18836448.

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Are these the elusive environmental and genetic factors that we have

been looking for as the trigger for UC/PSC?

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)