Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation

Yadong Qi; Jiamin He; Yawen Zhang; Qiwei Ge; Qiwen Wang; Luyi Chen; Jilei Xu; Lan Wang; Xueqin Chen; Dingjiacheng Jia; Yifeng Lin; Chaochao Xu; Ying Zhang; Tongyao Hou; Jianmin Si; Shujie Chen; Liangjing Wang

doi:10.1038/s41467-023-41827-0

Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation

Nat Commun. 2023 Sep 30;14(1):6121. doi: 10.1038/s41467-023-41827-0.

Authors

Yadong Qi^#^{1

2}, Jiamin He^#^{1

2}, Yawen Zhang^#^{1

2

3}, Qiwei Ge^#^{2

4}, Qiwen Wang^#^{1

2}, Luyi Chen^{3

5}, Jilei Xu^{1

2}, Lan Wang^{1

2}, Xueqin Chen^{1

2}, Dingjiacheng Jia^{2

4}, Yifeng Lin^{2

4}, Chaochao Xu^{2

4}, Ying Zhang^{2

4}, Tongyao Hou^{1

2}, Jianmin Si^{6

7

8}, Shujie Chen^{9

10

11}, Liangjing Wang^{12

13

14}

Affiliations

¹ Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
² Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.
³ Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁵ Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁶ Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. sijm@zju.edu.cn.
⁷ Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China. sijm@zju.edu.cn.
⁸ Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. sijm@zju.edu.cn.
⁹ Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. chenshujie77@zju.edu.cn.
¹⁰ Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China. chenshujie77@zju.edu.cn.
¹¹ Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. chenshujie77@zju.edu.cn.
¹² Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China. wangljzju@zju.edu.cn.
¹³ Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. wangljzju@zju.edu.cn.
¹⁴ Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. wangljzju@zju.edu.cn.

^# Contributed equally.

Abstract

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc^-/-), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5⁺ ISCs via Wnt/β-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bifidobacterium adolescentis*
Colon
Hot Temperature
Intestinal Mucosa
Intestines
Mice
Stem Cells