Genome-inferred metabolic interactions and microbial coexistence in aging skin microbiomes under nutrient stress

Summary: Abstract Body: Microbial communities adapt to their environment through complex metabolic interactions that drive species coexistence. We present a workflow to infer species interactions from microbial abundance dynamics, integrating metabolic niche overlap, abundance rank, functional overlap differences, and environmental associations. Applied to nutrient-stressed skin, this framework reveals that competition, kin selection, and antagonism predominantly shape coexistence mechanisms in skin aging. Stronger species correlations align with higher metabolic functional overlap, while positive abundance correlations inversely relate to phylogenetic distance. Aging reduces key species like Cutibacterium acnes and Staphylococcus epidermidis while increasing stress-resistant genera such as Moraxella and Chryseobacterium. Aging also shifts metabolic functions, enhancing drug resistance and xenobiotic biodegradation while reducing carbohydrate metabolism and glycan biosynthesis. Cutibacterium acnes competes via energy metabolism, while Moraxella thrives through niche differentiation, particularly in nucleotide metabolism. Antagonistic resistance, such as polyketide metabolism, aids species like Streptococcus and Cutibacterium in countering competition. This workflow provides insights into microbial coexistence and its implications for host health. Zhiming Guo¹, Zhiming Li⁴, Chongyin Han¹, Jinhong He³, Deyi Yin², Xiangping Tan², Jingjing Xia¹, Lianyi Han¹ 1. Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Shanghai, Shanghai, China. 2. South China Botanical Garden, Guangzhou, Guangdong, China. 3. Guangzhou Institute of Forestry and Landscape Architecture, Guangzhou, China. 4. School of Life Sciences, Fudan University, Shanghai, Shanghai, China. Bioinformatics, Computational Biology, and Imaging