Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models.
Sci Rep
; 12(1): 11516, 2022 07 07.
Article
en En
| MEDLINE
| ID: mdl-35799048
ABSTRACT
A strong association between exposure to the common harmful algal bloom toxin microcystin and the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to the cyanotoxin microcystin-LR may alter the host resistome. We show that the mice exposed to microcystin-LR had an altered microbiome signature that harbored antibiotic resistance genes. Host resistome genotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin-LR exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment of several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL-7 and TLR2. Microcystin-LR exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome following microcystin-LR exposure and its connection to host immune status and antimicrobial resistance that can be crucial to understand treatment options with antibiotics in microcystin-exposed subjects in clinical settings.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microcistinas
/
Microbioma Gastrointestinal
/
Inmunosenescencia
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM