Amoxicillin-induced gut dysbiosis influences estrous cycle in mice and cytokine expression in the ovary and the caecum

Am J Reprod Immunol. 2020 Jul;84(1):e13247. doi: 10.1111/aji.13247. Epub 2020 May 10.

Abstract

Problem: Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin-induced gut dysbiosis and its influence on the oestrous cycle in mice.

Method of study: Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL-1β and IL-10 genes and histological analysis.

Results: Amoxicillin-treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS-treated group indicating that amoxicillin treatment-induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin-induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL-1β was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL-10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non-dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non-dysbiotic mice.

Conclusion: The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.

Keywords: amoxicillin; dysbiosis; immune response; intestinal dysbiosis; oestrous cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / adverse effects*
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Cecum / physiology*
  • Cytokines / metabolism
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Dysbiosis / etiology
  • Dysbiosis / immunology*
  • Estrous Cycle / drug effects*
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gene Expression Regulation
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, 129 Strain
  • Ovary / physiology*

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Interleukin-1beta
  • Interleukin-10
  • Amoxicillin