TY - CONF

T1 - The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

AU - Rune, Ida

AU - Nielsen, Dennis Sandris

AU - Hansen, Axel Jacob Kornerup

AU - Ellekilde, Merete

AU - Lykkesfeldt, Jens

AU - Hansen, Camilla Hartmann Friis

AU - Rolin, BC

PY - 2011/11

Y1 - 2011/11

N2 - BackgroundRecent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance.Study setup40 C57BL/6NTac mice were randomized into 3 different groups prior to their birth. Mothers of groups 1 and 2 received a high fat diet whilst mothers of the 3rd group received a low fat diet. Mothers of group 1 also received ampicillin in their drinking water to prevent the pups from establishing a normal gut flora. At 5 weeks of age antibiotic treatment was ceased but was reintroduced at 11 weeks of age, where groups 1 and 2 were subdivided into each two sub-groups. One sub-groups of each group received antibiotic treatment until sacrifice of all animals at age 17 weeks.Oral glucose tolerance test (OGTT) was performed at weeks 5, 11 and 16 of age along with faecal sampling which would undergo denaturing gradient gel electrophoresis (DGGE).ResultsAt 5 weeks of age the area under the curve (AUC) of group 1 receiving antibiotic treatment was significantly lower than the AUC of group 2 (p<0.01**) for the OGTT. At 11 weeks of age this different could not be demonstrated between the two groups (p=0.8444). At 16 weeks of age no significant difference could be demonstrated in spite of treatment of sub-groups (p=0.2772).DGGE of samples obtained at 5 an 16 weeks of age respectively clustered according to treatment. At week 11 of age no clustering was evident.DiscussionOur results substantiate the theory implying an effect of gut microbiota on glucose tolerance. Furthermore, it seems evident that a window of opportunity for altering the host-microbial interaction response exists only in early life when host immunity is still developing. Finally, it is also clear that the impact on glucose tolerance ceases when antibiotic treatment is terminated. Further investigations into this area will be necessary to understand the underlying mechanism for these findings.

AB - BackgroundRecent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance.Study setup40 C57BL/6NTac mice were randomized into 3 different groups prior to their birth. Mothers of groups 1 and 2 received a high fat diet whilst mothers of the 3rd group received a low fat diet. Mothers of group 1 also received ampicillin in their drinking water to prevent the pups from establishing a normal gut flora. At 5 weeks of age antibiotic treatment was ceased but was reintroduced at 11 weeks of age, where groups 1 and 2 were subdivided into each two sub-groups. One sub-groups of each group received antibiotic treatment until sacrifice of all animals at age 17 weeks.Oral glucose tolerance test (OGTT) was performed at weeks 5, 11 and 16 of age along with faecal sampling which would undergo denaturing gradient gel electrophoresis (DGGE).ResultsAt 5 weeks of age the area under the curve (AUC) of group 1 receiving antibiotic treatment was significantly lower than the AUC of group 2 (p<0.01**) for the OGTT. At 11 weeks of age this different could not be demonstrated between the two groups (p=0.8444). At 16 weeks of age no significant difference could be demonstrated in spite of treatment of sub-groups (p=0.2772).DGGE of samples obtained at 5 an 16 weeks of age respectively clustered according to treatment. At week 11 of age no clustering was evident.DiscussionOur results substantiate the theory implying an effect of gut microbiota on glucose tolerance. Furthermore, it seems evident that a window of opportunity for altering the host-microbial interaction response exists only in early life when host immunity is still developing. Finally, it is also clear that the impact on glucose tolerance ceases when antibiotic treatment is terminated. Further investigations into this area will be necessary to understand the underlying mechanism for these findings.

KW - Former LIFE faculty

KW - Type 2 diabetes

KW - Tarmflora

KW - immunitet

M3 - Poster

Y2 - 16 November 2011

ER -