2021/04/09
Keio University
A research group centered at Keio University and Kyodo Milk Co., Ltd. has revealed that polyamines from gut bacteria play a crucial role in maintaining the health of the colonic mucosa by acting on intestinal epithelial cells and macrophages. This achievement is the result of a research group led by Professor Koji Hase of the Faculty of Pharmacy at Keio University, and Atsuo Nakamura, a researcher at Kyodo Milk Co., Ltd. (and a joint researcher at the Keio University Faculty of Pharmacy), and Mitsuharu Matsumoto, a principal researcher.
Polyamines (putrescine, spermidine, and spermine) are components universally present in the cells of all living organisms and are essential for cell proliferation and maintaining function. The gut microbiota is presumed to be one of the important sources of polyamines. Principal researcher Matsumoto and his colleagues have previously reported that higher polyamine concentrations in the intestinal lumen extend the lifespan of mice. However, the extent to which polyamines from the gut microbiota are actually absorbed by the body and what physiological effects they have were not well understood.
In this study, the research group created gnotobiotic mice colonized separately with either wild-type *E. coli* that produces putrescine (putrescine-producing bacteria) or a non-producing *E. coli* strain in which the putrescine synthesis genes were disrupted (non-producing bacteria), and evaluated the effects of putrescine derived from gut bacteria. The results showed that only in mice colonized with the putrescine-producing bacteria was the proliferation of colonic epithelial cells promoted and the differentiation of anti-inflammatory macrophages in the colonic mucosal tissue induced. It was also revealed that exogenous putrescine is taken up into these cells and converted to spermidine, and that the aforementioned effects occur via the hypusination of eukaryotic translation elongation factor eIF5A, a process involving this spermidine. Furthermore, when colitis was induced in these gnotobiotic mice with a chemical agent, the mice colonized with putrescine-producing bacteria showed a mitigation of the colitis disease score and an increased survival rate compared to the mice colonized with non-producing bacteria.
Based on these findings, it was demonstrated that putrescine, a metabolite of the gut microbiota, is transferred to the host, converted into spermidine within cells, and contributes to the health of the colonic mucosal layer through the action of spermidine via eIF5A. This also represents the first presentation of the concept of bioactive substance production through "symbiotic metabolism," a process involving both the gut microbiota and the host.
The results of this research were published in the international academic journal "Nature Communications" (online edition) on April 8, 2021.
For the full press release, please see below.