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Expression of Microbiota, Toll-like Receptors, and Their Regulators in the Small Intestinal Mucosa in Celiac Disease

Kalliomäki, Marko*; Satokari, Reetta; Lähteenoja, Hannu; Vähämiko, Sanna§; Grönlund, Juhani*; Routi, Taina*; Salminen, Seppo§

Journal of Pediatric Gastroenterology & Nutrition: June 2012 - Volume 54 - Issue 6 - p 727–732
doi: 10.1097/MPG.0b013e318241cfa8
Original Articles: Gastroenterology

Objectives: Less than one-tenth of the carriers of the risk genes HLA-DQ2 or HLA-DQ8 develop celiac disease, suggesting that other genetic and environmental factors are important in the pathogenesis. The role of gut microbiota has been addressed previously with inconsistent findings. Our aim was to evaluate microbiota, its receptors (Toll-like receptors [TLRs]), and regulators of the TLRs in the small intestinal mucosa in celiac disease.

Methods: Microbiota was analyzed by quantitative polymerase chain reaction (total bacteria and 10 bacterial group- and species-specific primers) and gene expression of interleukin-8 (IL-8), TLR2, TLR3, TLR4, TLR5, TLR9, and regulators of TLRs, Toll-interacting protein (TOLLIP), and single immunoglobulin IL-1R–related molecule, by relative quantitative reverse transcription-polymerase chain reaction in 10 children with celiac disease (untreated celiacs), 9 children with normal small intestinal mucosa (controls), and 6 adults with celiac disease with normal small intestinal mucosa after following a gluten-free diet (treated celiacs).

Results: Small intestinal microbiota was comparable among controls, untreated celiacs, and treated celiacs. Expression of IL-8 mRNA, a marker of intestinal inflammation, was significantly increased in untreated celiacs as compared with treated celiacs (P = 0.002) and controls (P = 0.001). Expression of TLR-2 mRNA was significantly decreased in untreated (P = 0.001) and treated (P = 0.03) celiacs, whereas expression of TLR-9 mRNA was increased in untreated celiacs (P = 0.001) as compared with controls. Expression of TOLLIP mRNA was downregulated in untreated celiacs as compared with controls (P = 0.02).

Conclusions: Altered gene expression of TLR2, TLR9, and TOLLIP in small intestinal biopsies in celiac disease suggests that microbiota-associated factors may be important in the development of the disease.

*Department of Pediatrics

Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland

Department of Internal Medicine, University of Turku, Turku

§Functional Foods Forum.

Address correspondence and reprint requests to Dr Marko Kalliomäki, Department of Pediatrics, University of Turku and Turku University Hospital, PO Box 52, FI-20521 Turku, Finland (e-mail: marko.kalliomaki@utu.fi).

Received 16 July, 2011

Accepted 11 November, 2011

The authors received funding from the ESPGHAN Infant Nutrition Award, the Päivikki and Sakari Sohlberg Foundation, the Paediatric Research Foundation, and the Hospital District of Southwest Finland.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN