Animal epithelia are heavily colonized by bacteria. One important protein activated by an unbalanced microbiome via bacterial uracil is DUOX. DUOX attacks pathogenic bacteria. Because DUOX is a evolutionary conserved protein, research on DUOX has broad implications: in humans, DUOX plays an important part in the etiology of inflammatory bowel disease (1). In this study, we tested if activation of DUOX can cause gut inflammation, using the model insect Manduca sexta. Further, we examined if this inflammation can be visualized directly on larvae using MRI...

We established MRI and PET imaging techniques with gadobenic-acid and 2-deoxy-2-(18F)fluoro-D-glucose respectively, methods firstly applied to insects, to detect gut inflammation (p = 161). Bacillus thuringiensis subsp. aizawai infected animals were used as a positive control. Production of HOCl was proven by conversion of R19s into its fluorescence state (2-4).Additionally, intestinal transcription levels of DUOX were quantified via RT-PCR.

The structure and function of M. sexta DUOX are similar to human or Drosophila DUOX (Fig. 1-3). In M. sexta DUOX is expressed in the foregut and hindgut but not in the midgut. The occurrence of HOCl in the gut of uracil fed but not in control larvae was demonstrated (Fig. 4). Using MRI and PET, we detected a significant difference in gut wall thickness (p = 0.029) in contrast-enhanced bowels and SUVmax in the anterior region (p = 0.0004) of larvae fed with uracil...

Our data suggest that M. sexta DUOX is functionally similar to human DUOX. We present strong indications, that M. sexta DUOX is activated via uracil, and catalyzes the production of HOCl, which causes gut inflammation. This new aspect should be considered and may lead to new strategies understanding inflammatory bowel diseases.

Anton George Müller, Institute of General Zoology and Developmental Biology Cellular Detection and Defense Processes, Justus-Liebig-University of Giessen, Stephanstraße 24, D-35390 Giessen, Germany. Phone: 049641 - 99 35604, e-mail: [email protected]

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