New Mechanism for Anti-Infection Effects of Dietary Fiber

New research in mice has uncovered a previously unknown interaction between molecules derived from dietary fiber and an immune cell protein, which triggers protection against infection with Salmonella bacteria. Hitoshi Tsugawa of Keio University School of Medicine in Tokyo, Japan, and colleagues present their findings in a paper publishing on September 29^th, 2020 in the open-access journal PLOS Biology. 

Previous research has shown that microbes in the gut break down ingested fiber into molecules known as short-chain fatty acids. Short-chain fatty acids appear to protect against pathogens like Salmonella by influencing the activity of immune cells, including macrophages. However, the mechanisms by which short-chain fatty acids interact with immune cells remained unclear. 

To better understand the protective role of short-chain fatty acids, the researchers performed a series of laboratory experiments. First, they attached short-chain fatty acids to the surface of synthetic “nano-beads,” and exposed the tiny structures to the contents of cells that have macrophage characteristics in order to determine which proteins in the cells interacted with the fatty acids. 

This procedure revealed that short-chain fatty acids can bind to a protein called apoptosis-associated speck-like protein (ASC)—a previously unknown interaction. ASC is part of the so-called inflammasome complex, a protein structure that helps activate the inflammatory response to suppress pathogens. Further experiments in macrophages showed that short-chain fatty acids protect against Salmonella infection by binding to ASC and thereby triggering inflammasome activation. 

The researchers confirmed and expanded their findings in experiments with mice. When Salmonella-infected mice were fed with short-chain fatty acids, or with their dietary fiber precursors, the fatty acids bound to ASC, triggered inflammasome activation, and prolonged the mice’s survival.

These results provide new insights into the effects of dietary fiber on the immune system. Further research will be needed to determine the applicability of these findings to humans, and to investigate other potential effects of short-chain fatty acids on the immune system.

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Funding: This work was supported by AMED-CREST from the Japan Agency for Medical Research and Development, AMED (to YK, grant no.: JP17gm0710010). The S. Typhimurium infection model in this work was partly supported by Cross-ministerial Strategic Innovation Promotion Program (SIP), “Technologies for creating next-generation agriculture, forestry and fisheries” (funding agency: Bio-oriented Technology Research Advancement Institution, NARO) (to HT). Infrastructures for imaging mass spectrometry and metabolomics were supported in part by Ryoshoku-Kenkyukai and JST ERATO Suematsu Gas Biology Project (M.S.) until FY2015. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

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