The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.
OBJECTIVE
Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice.


METHODS
21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected.


RESULTS
We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4+cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells.


CONCLUSIONS
Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii.
Department of Gastroenterology and Internal Medicine, Medical University of Bialystok ul, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland. Electronic address: danilukj@poczta.onet.pl.
Jaroslaw
J
Daniluk
Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok ul, J. Waszyngtona 17, 15-274 Bialystok, Poland.
Urszula
U
Daniluk
Department of Haematological Diagnostics, Medical University of Bialystok ul, J. Waszyngtona 15A, 15-269 Bialystok, Poland.
Malgorzata
M
Rusak
Department of Haematological Diagnostics, Medical University of Bialystok ul, J. Waszyngtona 15A, 15-269 Bialystok, Poland.
Milena
M
Dabrowska
Department of Medical Pathomorphology, Medical University of Bialystok ul, J. Waszyngtona 13, 15-269 Bialystok, Poland.
Joanna
J
Reszec
Genomic Laboratory, DNA Research Center ul, Mickiewicza 31, 60-385 Poznan, Poland.
Magdalena
M
Garbowicz
Genomic Laboratory, DNA Research Center ul, Mickiewicza 31, 60-385 Poznan, Poland.
Kinga
K
Huminska
Department of Gastroenterology and Internal Medicine, Medical University of Bialystok ul, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland.
Andrzej
A
Dabrowski
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D001769:Blood / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D016131:Lymphocyte Subsets; D008297:Male; D008810:Mice, Inbred C57BL; D010406:Penicillins / Q000008:administration & dosage*
D000900:Anti-Bacterial Agents; D010406:Penicillins
Lymphocytes; Microbiota; Parabacteroides goldsteinii; Penicillin