Periodic Reporting for period 1 - IMPRINT (Immunological and Microbiota Priming of the Response to Infection)
Okres sprawozdawczy: 2022-03-21 do 2024-03-20
1. To evaluate the impact of the gut microbiota on the susceptibility to intestinal infection in adulthood
2. To establish whether microbiota-induced immune cells in the intestine influence susceptibility and immune response to intestinal infection in adulthood
3. To identify specific gut microbes and/or microbial metabolites during weaning that promote induction of intestinal immune cells and modulate subsequent susceptibility to intestinal infection in adulthood
This project found that exposure to antibiotics during early-life reduced early colonization of an intestinal pathogen (Citrobacter rodentium) in male mice during adulthood in addition to a reduced inflammatory response in the intestine. This may be due, in part, to changes induced by the early-life gut microbiota on intestinal epithelial cells. Collectively, the project found a role of the early-life gut microbiota on the immune response to infection in adulthood.
During months 7-21 of the action involved conducting of experiments directly related to the proposed work. Three independent sets of experiments were conducted during this 14 month period. Briefly, muring mothers and pups were treated with or without a cocktail of antibiotics from day 5-28 of life after which the offspring were weaned into separate cages. At 8 weeks of life, mice were infected with 10(9) colony-forming units of Citrobacter rodentium, by oral gavage, and fecal samples were collected every second day for up to 14 days to test for pathogen abundance. Following infection, intestinal inflammatory genes, inflammatory cytokines, tissue lymphocyte proportions were all assessed at either day 5 (short term infection) or day 10/14 (long-term infection).
In brief, we found that exposure to early-life antibiotics reduced colonization of C. rodentium in the first 3 days of infection, only in male mice, however pathogen colonization was similar between both antibiotic treated and non-treated mice after 3 days. Inflammatory gene expression was also also reduced in antibiotic exposed mice compared with non-antibiotic treated, infected mice.