Abstract
The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.
Highlights
The complex ecosystem of the mammalian intestine consists of a dense and diverse mutualistic microorganism known as the intestinal microbiota has been at the forefront of research in human and animal health [1,2]
We found that mice treated with E. coli displayed higher aryl hydrocarbon receptor (AhR) expression (Fig 1A), implying the regulatory role of the AhR pathway in E. coli-induced mastitis pathogenesis
We showed that E. coli treatment increased the mastitis inflammation score (Fig 1B and 1C), MPO activity (Fig 1D) and consistent expression of cytokines compared to the control group (Fig 1E and 1F), while Ficz pretreatment decreased the E. coli-induced inflammatory profiles compared to the E. coli treatment (Fig 1B–1F)
Summary
The complex ecosystem of the mammalian intestine consists of a dense and diverse mutualistic microorganism known as the intestinal microbiota has been at the forefront of research in human and animal health [1,2]. Emerging evidence has indicated that disruption of the fragile balance within the intestinal microbiota, termed dysbiosis, is involved in tremendous inflammatory and metabolic diseases in both intestine proximal and distant organs [1,3]. Our recent study revealed that disrupting the intestinal microbiota by antibiotic treatment increased susceptibility to Staphylococcus aureus-induced mastitis in mice [7]. These results suggest that the intestinal microbiota plays a significant role in mastitis progression [6,7,8], the way in which the intestinal microbiota mediates mastitis development and the potential molecular mechanisms, remain elusive
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
