Gut microbiota recovery and immune response in ampicillin-treated mice

• Published in: Research in veterinary science 2018-06, Vol.118, p.357-364
• Main Authors: Castro-Mejía, Josué L., Jakesevic, Maja, Fabricius, Niels F., Krych, Łukasz, Nielsen, Dennis S., Kot, Witold, Bendtsen, Katja M., Vogensen, Finn K., Hansen, Camilla H.F., Hansen, Axel K.
• Format: Article
• Language: English
• Subjects: Ampicillin; Ampicillin - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacteroidales; Bacteroidetes; Clostridia; Colonization; Cytokines; Deoxyribonucleic acid; DNA; Drinking water; Enterobacteriaceae; Environment; Firmicutes; Gammaproteobacteria; Gastrointestinal Microbiome - immunology; Germfree; Housing; Immune response; Immune system; Immunoregulation; Intestinal microflora; Lymphocytes; Lymphocytes T; Mice; Microbiota; Microorganisms; Natural killer cells; Parameter sensitivity; Penicillin; Proteobacteria; Rodents; Studies; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2018.03.013

Ampicillin is applied in rodents to induce a temporarily depleted microbiota. To elucidate whether bacteria are just temporarily suppressed or fully eliminated, and how this affects the re-colonisation process, we compared the microbiota and immune system in conventionally housed untreated mice with newly weaned ampicillin treated mice subsequently housed in either a microbe containing environment or in an isolator with only host associated suppressed bacteria to recolonize the gut. Two weeks ampicillin treatment induced a seemingly germ-free state with no bacterial DNA to reveal. Four weeks after treatment caeca were still significantly enlarged in both treated groups, but bacteria re-appeared even in isolator housed mice. While some suppressed bacteria were able to recover and even dominate the community, the abundances and composition were far from the untreated mice and differed between isolator and conventional housing. The treatment reduced the innate cytokine expressions at least for three weeks after treatment, and had a non-lasting reducing impact on the regulatory T cells, and a more lasting impact on the natural killer T cells. We conclude that temporary ampicillin treatment suppresses the majority but does not eliminate all the gut microbiota members. The re-colonisation process is as such influenced by both suppressed host associated bacteria and by environmental bacteria. Treated mice do not re-obtain a complex gut microbiota comparable to untreated mice, and the immune response and gut morphology reflect this. This is a concern when comparing host parameters sensitive to microbial regulation after an antibiotic-induced temporarily “germ-free” state. [Display omitted] •Ampicillin treatment induces an apparently germ-free status of mice.•A microbiota will re-colonize even in mice isolated in germ-free surroundings.•Post-treatment microbiota composition is highly dependent on the environment.•Post-treatment microbiota is significantly different from non-treated mice.•The immune system of treated mice differs from non-treated mice after treatment.