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. 2020 Sep 2;11(5):1450-1474.
doi: 10.1080/19490976.2020.1763770. Epub 2020 Jun 9.

Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically

Junli Ma  1 , Ying Hong  1 , Ningning Zheng  1 , Guoxiang Xie  2 , Yuanzhi Lyu  3 , Yu Gu  1 , Chuchu Xi  1 , Linlin Chen  1 , Gaosong Wu  1 , Yue Li  4 , Xin Tao  1 , Jing Zhong  1   5 , Zhenzhen Huang  6 , Wenbin Wu  6 , Lin Yuan  6 , Min Lin  6 , Xiong Lu  6 , Weidong Zhang  1   7 , Wei Jia  8   9 , Lili Sheng  1 , Houkai Li  1
Affiliations

Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically

Junli Ma et al. Gut Microbes. .

Abstract

Aging is usually characterized with inflammation and disordered bile acids (BAs) homeostasis, as well as gut dysbiosis. The pathophysiological changes during aging are also sexual specific. However, it remains unclear about the modulating process among gut microbiota, BA metabolism, and inflammation during aging. In this study, we established a direct link between gut microbiota and BA profile changes in the liver, serum, and four intestinal segments of both sexes during aging and gut microbiota remodeling by co-housing old mice with young ones. We found aging reduced Actinobacteria in male mice but increased Firmicutes in female mice. Among the top 10 altered genera with aging, 4 genera changed oppositely between male and female mice, and most of the changes were reversed by co-housing in both sexes. Gut microbiota remodeling by co-housing partly rescued the systemically dysregulated BA homeostasis induced by aging in a sex- and tissue-specific manner. Aging had greater impacts on hepatic BA profile in females, but intestinal BA profile in males. In addition, aging increased hepatic and colonic deoxycholic acid in male mice, but reduced them in females. Moreover, muricholic acids shifted markedly in the intestine, especially in old male mice, and partially reversed by co-housing. Notably, the ratios of primary to secondary BAs in the liver, serum, and all four intestinal segments were increased in old mice and reduced by co-housing in both sexes. Together, the presented data revealed that sex divergent changes of gut microbiota and BA profile in multiple body compartments during aging and gut microbiota remodeling, highlighting the sex-specific prevention and treatment of aging-related disorders by targeting gut microbiota-regulated BA metabolism should particularly be given more attention.

Keywords: Aging; bile acid composition; gut microbiota; inflammation; sex difference.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Histological and phenotypic changes in young and old mice of both sexes.
Figure 2.
Figure 2.
BA profile in the liver, serum, and intestine of young and old mice.
Figure 3.
Figure 3.
Aging induces gut microbiota disbalance in both sexes.
Figure 4.
Figure 4.
Histological and phenotypic changes in old mice after co-housing.
Figure 5.
Figure 5.
Co-housing improves gut microbiota disbalance induced by aging in both sexes.
Figure 6.
Figure 6.
BA profile in the liver, serum, and intestine of male and female mice after co-housing.
Figure 7.
Figure 7.
Hepatic BAs metabolism-related gene expression in male (a) and female (b) mice. *p< .05 and **p < .01 compared with young group; # p < .05 compared with old group. n = 5–8 mice per group.
Figure 8.
Figure 8.
Sex difference in the concentration of certain BAs in the liver, serum, and cecal contents. &p < .05, &&p < .01 compared with female group. n = 5–10 mice per group.
Figure 9.
Figure 9.
Gut microbiota remodeling by co-housing reverses the dysregulation of systemic BA homeostasis induced by aging.
See this image and copyright information in PMC

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