A fiber-enriched diet alleviates Staphylococcus aureus-induced mastitis by activating the HDAC3-mediated antimicrobial program in macrophages via butyrate production in mice

PLoS Pathog. 2023 Jan 19;19(1):e1011108. doi: 10.1371/journal.ppat.1011108. eCollection 2023 Jan.

Abstract

Mounting evidence suggests that the gut microbiota plays an important role in the pathogenesis of mastitis, an important disease affecting the health of lactating women and the development of the dairy industry. However, the effect of the regulation of the gut microbiota by dietary components on mastitis development remains unknown. In this study, we found that a fiber-enriched diet alleviated Staphylococcus aureus (S. au)-induced mastitis in mice, which was dependent on the gut microbiota as depletion of the gut microbiota by antibiotics abolished this protective effect. Likewise, fecal microbiota transplantation (FMT) from high-inulin (HI)-treated mice (HIF) to recipient mice improved S. au-induced mastitis in mice. Consumption of an HI diet and HIF increased fecal short-chain fatty acid (SCFA) levels compared with the control group. Moreover, treatment with SCFAs, especially butyrate, alleviated S. au-induced mastitis in mice. Mechanistically, consumption of an HI diet enhanced the host antimicrobial program in macrophages through inhibiting histone deacetylase 3 by the production of butyrate. Collectively, our results suggest that modulation of the gut microbiota and its metabolism by dietary components is a potential strategy for mastitis intervention and serve as a basis for other infectious diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Butyrates*
  • Diet
  • Dietary Fiber
  • Female
  • Lactation
  • Macrophages
  • Mastitis* / therapy
  • Mice
  • Staphylococcus aureus

Substances

  • Anti-Bacterial Agents
  • Butyrates
  • histone deacetylase 3
  • Dietary Fiber

Grants and funding

NZ, YF and XH were supported by the National Natural Science Foundation of China (https://isisn.nsfc.gov.cn/egrantweb/) with grant number of 31972749, 32122087 and 32102738 respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.