From Culture to Metagenomics: How Methodological Advances Reshape Our Understanding of the Oral Microbiota of Venomous Snakes

Abstract

Venomous snakes constitute ecologically significant and medically relevant organisms due to the risks associated with their bites, which frequently result in secondary infections. The oral microbiota of these reptiles plays a crucial role in the pathogenesis of such infections; however, its diversity and clinical implications remain insufficiently characterized. This is the first comprehensive review to systematically trace the methodological evolution in snake oral microbiota research, documenting the paradigm shift from traditional culture-dependent techniques to advanced culture-independent approaches, including next-generation sequencing and metagenomics. Our analysis uniquely demonstrates the transformative impact of these technological advances on bacterial diversity identification and antimicrobial resistance gene detection in venomous species. Environmental factors, captivity conditions, and venom composition significantly influence microbial community structure and resistance profiles. These intricate interactions are essential for improving clinical management of snakebite infections, informing empirical antibiotic therapy protocols, and guiding antivenom production strategies. Additionally, the potential of snake oral microbiota as a source of novel bioactive compounds represents an emerging area of bioprospecting research. This review uniquely bridges microbiology, venomics, and clinical medicine, demonstrating the necessity for integrative, multidisciplinary approaches to fully elucidate the ecological and biomedical significance of oral microbial communities in venomous snakes.