Effect of early-life gut mucosal compromise on disease progression in NOD mice

Katja M. Bendtsen; Camilla HF Hansen; Lukasz Krych; Karsten Buschard; Helene Farlov; Axel K. Hansen

Effect of early-life gut mucosal compromise on disease progression in NOD mice

Katja M. Bendtsen^*, Camilla HF Hansen, Lukasz Krych, Karsten Buschard, Helene Farlov, Axel K. Hansen

^*Corresponding author af dette arbejde

3 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Comparative Medicine
Vol/bind	67
Udgave nummer	5
Sider (fra-til)	388-399
Antal sider	12
ISSN	1532-0820
Status	Udgivet - 2017

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title = "Effect of early-life gut mucosal compromise on disease progression in NOD mice",

abstract = "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.",

keywords = "DSS: dextran sulfate sodium, NOD, nonobese diabetic, OTU, operational taxonomic unit, T, regulatory T cells",

author = "Bendtsen, {Katja M.} and Hansen, {Camilla HF} and Lukasz Krych and Karsten Buschard and Helene Farlov and Hansen, {Axel K.}",

year = "2017",

language = "English",

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pages = "388--399",

journal = "Comparative Medicine",

issn = "1532-0820",

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TY - JOUR

T1 - Effect of early-life gut mucosal compromise on disease progression in NOD mice

AU - Bendtsen, Katja M.

AU - Hansen, Camilla HF

AU - Krych, Lukasz

AU - Buschard, Karsten

AU - Farlov, Helene

AU - Hansen, Axel K.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - DSS: dextran sulfate sodium

KW - NOD, nonobese diabetic

KW - OTU, operational taxonomic unit

KW - T, regulatory T cells

M3 - Journal article

AN - SCOPUS:85029859619

SN - 1532-0820

VL - 67

SP - 388

EP - 399

JO - Comparative Medicine

JF - Comparative Medicine

IS - 5

ER -

Effect of early-life gut mucosal compromise on disease progression in NOD mice

Abstract

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