From niche to niche: investigating microbial communities and their specialised metabolite gene clusters in human...

Diverse microbial communities within the human microbiome perform vital functions which influence both health and disease in hosts. Specialized metabolites produced by microbes via biosynthetic gene clusters (BGCs) drive ecological interactions and offer possibilities for therapeutic application. The biosynthetic capabilities of microorganisms present in human microbiomes are still mostly unexplored despite metagenomics advancements. The study examines the variety of microbial communities and BGC locations through metagenomic data from 1,191 samples across eight human microbiomes taken from the IMG/M database. Kraken2 executed taxonomic classification while antiSMASH v6.1.1 identified BGCs. The study used BiG-SCAPE to build a sequence similarity network while Bracken and Pavian tools analyzed microbial diversity. A total of 25,681 BGCs were identified, of which 97.5%, showed no significant match to existing clusters in MIBIG database, indicating substantial potential for novel biosynthetic discoveries . Showing no match to existing clusters in the MIBiG database which shows huge potential for new biosynthetic discoveries. New strains were discovered that produce unique RiPPs, NRPs, and siderophores primarily within the microbiomes of the large intestine, oral cavity, and skin. The large intestine showed maximum microbial and biosynthetic diversity compared to other areas while the biliary tract and nasal cavity displayed minimal diversity. New BGCs associated with antibiotic, cytotoxic, and immune-modulating functions present potential therapeutic uses. The investigation uncovers essential information about how microbial communities develop specific functions within various body regions. Uncharacterized BGC discoveries present new opportunities for drug development and treatments that target microbiomes.