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서울대학교

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J. Hazard. Mater., Jun 11 2025, 495 S0304-3894(25)01818-7 | https://doi.org/10.1016/j.jhazmat.2025.138902 An integrated microbial genome-wide association studies-based characterization of nitric oxide homeostasis by probiotic Bacillus subtilis on aging and neurodegeneration using Caenorhabditis elegans and mouse models

Anna Kang ^a, Hye Jin Choi^a, Woong Ji Lee ^a, Min-Geun Kang ^a, Eunsol Seo ^a, Daniel Junpyo Lee ^a, Youbin Choi ^a, Seon-hui Son ^a, Min-Jin Kwak ^b,c, Kwangcheol Casey Jeong ^b,c, Sangnam Oh ^d, Younghoon Kim^a

^aDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, South Korea
^bEmerging Pathogens Institute, University of Florida, Gainesville, FL 32611, USA
^cDepartment of Animal Sciences, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA
^dDepartment of Food and Nutrition, Jeonju University, Jeonju 55069, South Korea

Corresponding authors : Sangnam Oh, Younghoon Kim

Abstract

Microbial nitric oxide (NO) metabolism plays a critical role in regulating host redox homeostasis, yet its probiotic relevance remains largely unexplored. In this study, we performed a genome-wide phenotypic screen of 3984 Bacillus subtilis 168 (B. subtilis 168) gene deletion strains in Caenorhabditis elegans (C. elegans), identifying 12 core genetic factors linked to aging modulation. Among these, nosA (nitric oxide synthase) and yojO (putative nitric oxide reductase) were prioritized for validation based on their consistent host phenotypic effects and defined roles in NO regulation. Treatment with wild-type B. subtilis 168 extended C. elegans lifespan by 20 %, enhanced locomotor activity and chemotaxis index by 30-40 %, and reduced amyloid-beta accumulation by over 35 %. In contrast, ΔnosA and ΔyojO strains abolished these benefits, resulting in lifespan and behavior indices comparable to Escherichia coli OP50. In a BSO-induced oxidative stress mouse model, B. subtilis 168 administration significantly improved performance in Y-maze, open field, and novel object recognition tasks, whereas ΔnosA and ΔyojO groups exhibited diminished behavioral recovery and no improvement in cognitive outcomes. These findings demonstrate that microbial NO synthesis and detoxification are critical for mediating the anti-aging and neuroprotective functions of B. subtilis. Our study highlights a genetically tractable framework for dissecting host-microbe interactions relevant to redox signaling and age-associated neurodegeneration.

논문정보

형식Research article
게재일2025년 06월 (BRIC 등록일 2025-06-16)
연구진국내(교신)+국외 연구진
분야 생명과학 > 미생물학

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