Exploring the Potential of Bacteroides Thetaiotaomicron in Modulating the Immune Response in Acute Myeloid Leukemia

BACKGROUND AND OBJECTIVESBacteroides thetaiotaomicron is proposed as a potential candidate for the next generation of probiotics. The ES-۸ and ES-D genes play crucial roles in activating and modulating the innate immune system against leukemia following bacterial exposure in the bone marrow. This study was designed to examine the effect of B. thetaiotaomicron and its derivatives on alterations in the expression of ES-۸ and ES-D genes, and their significance in modulating the severity of acute myeloid leukemia (AML).MATERIALS AND METHODThe impact of B. thetaiotaomicron, outer membrane vesicles (OMVs), inactivated bacteria, and supernatant treatments on the ES-۸ and ES-D gene expression in the KG-۱ cell line was analyzed using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. The Livak (ΔΔCT) method was employed to interpret the qRT-PCR results.The extraction and evaluation of outer membrane vesicles from gram-negative bacteria were performed using ultracentrifugation and ultrafiltration-based methods.RESULTS AND DISCUSSIONThe KG-۱ cell line showed a significant response to treatment with live and active B. thetaiotaomicron, particularly in ES-۸ and ES-D transcription. OMVs from this bacterium, at a concentration of ۵۰ μg/ml, significantly intensified the expression of the ES-۸ (p=۰.۰۱) and ES-D (p=۰.۰۲) genes. This effect was even more pronounced at a concentration of ۱۰۰ μg/ml. Inactivation at MOI ۱۰ (p=۰.۰۳) and MOI ۵۰ (p=۰.۰۰۳) significantly induced transcription of both genes. Additionally, a ۲۵% supernatant considerably augmented the transcriptional expression of ES-۸ (p=۰.۰۳۸) and ES-D (p=۰.۰۳۴) genes.CONCLUSIONOur findings suggest that OMVs at a concentration of ۱۰۰ μg/ml, inactivated bacteria, and supernatants of B. thetaiotaomicron play a crucial role in shaping the immune response and could be considered as potential postbiotic and paraprobiotic candidates for further research. Moreover, our data indicate a significant reduction in the severity of acute myeloid leukemia in the erythroleukemia phase, affirming its potential as an effective adjuvant treatment for leukemia.

کلیدواژه ها:

B.thetaiotaomicron ، Acute myeloid leukemia ، Microbiota ، OMVs ، ES-۸ ، ES-D