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Effect of Early-life Gut Mucosal Compromise on Disease Progression in NOD Mice

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  • Katja M Bendtsen
  • Camilla Hf Hansen
  • Lukasz Krych
  • Karsten Buschard
  • Helene Farlov
  • Axel K Hansen
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Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus-reducing effect of this compound and subsequent increased host-bacterial contact would delay disease onset and decrease insulitis due to enhanced oral tolerance. However, disease incidence did not differ between groups, although median survival (time point when 50% of the mice are still alive) of the control group was 184 d compared with 205 d for DSS-treated mice. Mean age at disease onset (that is, blood glucose of at least 12 mmol/L) was 164 d for control mice and 159 d for DSS-treated mice. In addition, 62.5% of control mice reached a blood glucose of 12 mmol/L before 30 wk of age compared with 59% in DSS-treated mice, which had a significant transient increase in serum insulin in week 4. No changes were found in immune cells collected from spleen, pancreatic lymph nodes, and mesenteric lymph nodes. Although mice received a low dose of DSS, the subsequent reduction in the diversity of the microbiota during weeks 4 through 6 led to increased cecal length and weight and, in week 13, a tendency toward decreased colon length, with increased leakage of LPS to the blood. We conclude that mucus reduction and subsequent increased host-bacterial contact did not affect overall disease progression in NOD mice.

OriginalsprogEngelsk
TidsskriftComparative Medicine
Vol/bind67
Udgave nummer5
Sider (fra-til)388-399
Antal sider12
ISSN1532-0820
StatusUdgivet - 1 okt. 2017

ID: 52603089