Volume 9 Number 1 2026
Probiotics as Unintended Vectors of Horizontal Gene Transfer, the Gut Resistome, and the Biosafety of Live Biotherapeutic Products
Md Saiyed Qutubul Alam 1, Md. Kawser 2*, Meer Sakib Hasan Shishir 2, Most. Samia Mahin Onty 2, Nafi Khan Rhine 1
Microbial Bioactives 9 (1) 1-8 https://doi.org/10.25163/microbbioacts.9110931
Submitted: 19 July 2026 Revised: 07 September 2026 Accepted: 16 September 2026 Published: 18 September 2026
Probiotics occupy an uneasy dual identity in modern medicine: prescribed to repair the very ecosystem that antibiotics disturb, they are, at the same time, living organisms capable of carrying and sharing resistance genes. This tension is the starting point of the present review, and it is one the field has arguably been slow to reckon with. Background: antimicrobial resistance (AMR) is projected to cause up to 10 million deaths annually by 2050, while the antibiotic development pipeline remains structurally stagnant, pushing clinical and research attention toward the gut microbiome as both a therapeutic target and a hidden reservoir of resistance genes. Methods: this review followed a structured narrative-synthesis approach broadly consistent with PRISMA reporting principles, screening peer-reviewed literature (2019-2026) indexed in PubMed, Scopus, and Web of Science across microbiology, pharmacology, and biomedical engineering, and synthesizing mechanistic, genomic, and translational evidence on horizontal gene transfer (HGT), mobile genetic elements, and probiotic biosafety. Results: the synthesis shows that the human gastrointestinal tract functions as a dynamic resistome in which conjugation, transformation, and transduction move antimicrobial resistance genes (ARGs) between commensals, probiotic strains, and opportunistic pathogens, frequently within the protected microenvironment of gut biofilms; that specific plasmid families (IncX4, IncI2, IncHI2) and genes (bla_CTX-M, mcr-1 to mcr-10, vanA/vanB, bla_KPC/bla_NDM) recur as high-risk determinants; and that phenotypic susceptibility testing, exemplified by the Multiple Antibiotic Resistance (MAR) index, systematically under-detects transmissible risk relative to whole-genome sequencing. Conclusion: intrinsic, chromosomally encoded resistance appears broadly compatible with probiotic safety, whereas plasmid- or transposon-borne acquired resistance genes constitute a disqualifying risk that phenotype alone cannot reveal; genomic screening, CRISPR-Cas-based subtractive and additive engineering, synthetic biocontainment, and AI-guided strain design together offer a plausible, though still maturing, route toward probiotics that restore the microbiome without expanding its resistome.
Keywords: Antimicrobial resistance; Horizontal gene transfer; Probiotics; Gut resistome; Mobile genetic elements; CRISPR-Cas; Live biotherapeutic products
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