Abstract
Oxidative stress is a pivotal trigger of immune responses and cellular dysfunction. The ruminant gastrointestinal tract (GIT) with complex microbial community demonstrated strong metabolic capabilities and close relationships with host oxidative stress. However, microbial antioxidant secondary metabolites in the GIT and their interactions with the host are still under-studied. Here, based on metagenome assembled genomes (MAGs) resources, deep learning, single-cell RNA-sequencing, and large number of protein-metabolites interactions inferring, we discovered the antioxidants from the microbial secondary metabolites and deciphered their potential interactions with the GIT epithelial cells. Totally 26,503 biosynthetic gene clusters (BGCs, 8,672 novel ones) were identified from 14,093 non-redundant MAGs distributed in 10 segments of cattle GIT. From the 436 BGCs’ products, totally 396 secondary metabolites were predicted into 5 categories of antioxidants using a custom-trained deep learning tool. The GIT epithelial cells showed higher expression of antioxidant genes among 1,006 clusters (belong to 126 cell types) of 51 tissues in cattle, especially the spinous cells and basal cells in the forestomach. Moreover, using metabolite-protein interaction inference, we predicted over 6 million pairs of interactive scores between 396 secondary metabolites and 14,976 marker proteins in the GIT cell types. Significant interactive scores between Cys-Cys-Cys and marker proteins participating in antioxidative metabolism such as CYC1, MGST1, GSTA1 in rumen and omasum spinous cells were highlighted. Our study presented a comprehensive computational framework for exploring natural antioxidants from MAGs, revealed the potential antioxidants from cattle GITs microbiota, and inferred their potential interactions with host GIT cell types, which will provide novel insights into the under-investigated antioxidant potential of cattle GIT microbiota and reshaping our comprehension of the symbiotic interplay between the gut microbiota and host antioxidant defense mechanisms.