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

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.

β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice

“…43 A decline in organoid formation in the crypts of older mice was also reported, which can be mediated by improved Wnt signaling. 12 The decreased Wnt levels at least partially explain the breakdown of the epithelial barrier and reduced goblet cell numbers. 44 The restoration of tight cortical junctions and intestinal barrier integrity is accompanied by the restoration of the Wnt-expressing ISC layer.…”

“…The activity of ISCs is regulated by the Wnt/β-catenin signaling pathway; the Wnt pathway has been shown to play a significant role in repairing the mechanical barrier of epithelial cell proliferation. 12…”

L‐arginine metabolism ameliorates age‐related cognitive impairment by Amuc_1100‐mediated gut homeostasis maintaining

“…The Illumina MiSeq platform (Illumina, San Diego, USA) was used to perform the DNA sequence according to the standard protocols of Shanghai MajorBio (China). The data were analyzed through the service majorbio platform ( cloud.majorbio.com ) as before (Qi et al., 2023 ). Briefly, OTU clustering of non‐repetitive sequences (excluding single sequences) was performed according to 97% similarity by Uparse (version 7.0.1090 http://drive5.com/uparse/ ), and chimeras were removed.…”