皮肤T细胞淋巴瘤(CTCL)是一组引起慢性炎症的皮肤归巢T细胞的淋巴增殖性疾病。这些疾病会导致免疫环境受损,这导致严重的感染和/或败血症由于菌群失调。在这项研究中,我们阐明了光疗治疗方案期间CTCL中发生的宿主-微生物相互作用,并确定了皮肤微生物群的调节是否可以有益地影响CTCL的病程.将EL4T细胞淋巴瘤细胞皮内移植到C57BL/6小鼠的背部。在存在或不存在局部抗生素治疗(新霉素,杆菌肽,和硫酸多粘菌素B)作为佐剂。评估皮肤的微生物定植与疾病严重程度和肿瘤生长相关。三联抗生素治疗显着延迟肿瘤发生(p=0.026),这延长了小鼠的存活时间(p=0.033)。分配给光疗剂PUVA,UVB,或者这些都没有,随着抗生素干预,显著降低肿瘤生长(p=0.0327,p≤0.0001,p≤0.0001)。使用Bray-Curtis模型计算的β多样性指数表明,抗生素处理后微生物种群显着差异(p=0.001)。通过抗生素治疗调节皮肤微生物组后,我们看到共生梭菌物种的增加,例如,落叶松科sp.(p=0.0008),反刍动物科。(p=0.0001)。,Blautiasp.(p=0.007),兼性病原体棒状杆菌的显着减少。(p=0.0009),Pelomonassp.(p=0.0306),链球菌。(p≥0.0001),假单胞菌。(p=0.0358),和Cutubacteriumsp.(p=0.0237)。有趣的是,我们观察到金黄色葡萄球菌的频率显着下降(p=0.0001),但葡萄球菌属的整体检测频率增加,表明抗生素治疗有助于恢复微生物平衡并增加非致病性葡萄球菌种群的数量。这些研究结果表明,通过局部抗生素治疗来调节微生物群有助于通过减少病原微生物的数量来恢复微生物平衡,which,反过来,减少慢性炎症,延迟肿瘤生长,并提高CTCL模型的生存率。这些发现支持在CTCL的疾病过程中调节微生物环境的基本原理,并表明其治疗潜力。
Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.