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 () and Liangjing Wang ()
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Yadong Qi: Zhejiang University School of Medicine
Jiamin He: Zhejiang University School of Medicine
Yawen Zhang: Zhejiang University School of Medicine
Qiwei Ge: Zhejiang University
Qiwen Wang: Zhejiang University School of Medicine
Luyi Chen: Zhejiang University School of Medicine
Jilei Xu: Zhejiang University School of Medicine
Lan Wang: Zhejiang University School of Medicine
Xueqin Chen: Zhejiang University School of Medicine
Dingjiacheng Jia: Zhejiang University
Yifeng Lin: Zhejiang University
Chaochao Xu: Zhejiang University
Ying Zhang: Zhejiang University
Tongyao Hou: Zhejiang University School of Medicine
Jianmin Si: Zhejiang University School of Medicine
Shujie Chen: Zhejiang University School of Medicine
Liangjing Wang: Zhejiang University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41827-0

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