Huang Wenqian, Zhang Yirong, Li Zhi, Li Minjie, Li Fangfang, Mortimer Monika, Guo Liang-Hong
College of Life Science, China Jiliang University, Hangzhou 310018, China 2 Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou 310018, China 3 College of Quality and Safety Engineering, China Jiliang University, Hangzhou 310018, China.
Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou 310018, China.
Nanomaterials (Basel). 2022 Sep 27;12(19):3377. doi: 10.3390/nano12193377.
Medical applications of nanotechnology are promising in creating efficient and targeted therapies. However, so far, nanodrug design has not taken into consideration possible effects on human microbiota. The beneficial functions of bacteria could be stimulated by nanodrugs while negative effects on beneficial bacteria could cause risks to human health. Here, simulated intestinal fluid (IF) was optimized for culturing a human commensal and probiotic bacterial strain, Lactobacillus casei, to study the effects of medically relevant NPs—Ag and hyaluronic acid-coated Au NPs (HA-Au NPs)—in conditions pertinent to the gastrointestinal tract. When cultivated either aerobically or anaerobically, the specific growth rates of L. casei were ~0.2 h−1 in IF and ~0.4 h−1 in the standard medium of lactobacilli (MRS). Ag NPs inhibited the growth of L. casei in IF at lower concentrations (EC50 ~ 65 and 15 mg/L in aerobic and anaerobic conditions, respectively) than in MRS (EC50 > 100 mg/L), likely caused by differences in the composition of the two media and different intrinsic growth rates of bacteria in IF and MRS. Ag NP dissolution in IF and MRS did not explain the differences in growth inhibition, implying NP-specific effects. HA-Au NPs were not growth-inhibitory to L. casei up to 250 mg/L. Still, both NPs at sub-growth-inhibitory concentrations suppressed the expression of bacteriocin genes in L. casei, suggesting an inhibitory effect of NPs on the probiotic properties of L. casei, i.e., its competitiveness in microbial communities. However, HA-Au NPs did not appear to affect or even stimulated the immunomodulatory properties of L. casei in human intestinal epithelial cells. Thus, medically relevant NPs at low, sub-bacteriostatic levels can affect the metabolism of beneficial human bacteria and potentially induce changes in the microbiota and immune signaling.
纳米技术在医学应用方面有望创造出高效且有针对性的治疗方法。然而，到目前为止，纳米药物设计尚未考虑到对人类微生物群可能产生的影响。纳米药物可能会刺激细菌的有益功能，而对有益细菌的负面影响可能会给人类健康带来风险。在此，对模拟肠液（IF）进行了优化，用于培养一种人类共生及益生菌菌株——干酪乳杆菌，以研究医学相关纳米颗粒（NPs）——银（Ag）和透明质酸包被的金纳米颗粒（HA-Au NPs）——在与胃肠道相关的条件下的影响。无论在需氧还是厌氧条件下培养，干酪乳杆菌在IF中的比生长速率约为0.2 h⁻¹，在乳酸菌标准培养基（MRS）中的比生长速率约为0.4 h⁻¹。Ag NPs在IF中比在MRS中能以更低浓度抑制干酪乳杆菌的生长（需氧和厌氧条件下的EC50分别约为65和15 mg/L，而在MRS中EC50 > 100 mg/L），这可能是由于两种培养基的成分差异以及IF和MRS中细菌不同的固有生长速率所致。Ag NPs在IF和MRS中的溶解情况并不能解释生长抑制的差异，这意味着存在NP特异性效应。HA-Au NPs在浓度高达250 mg/L时对干酪乳杆菌没有生长抑制作用。然而，两种处于亚生长抑制浓度的NPs都抑制了干酪乳杆菌中细菌素基因的表达，这表明NPs对干酪乳杆菌的益生菌特性有抑制作用，即其在微生物群落中的竞争力。然而，HA-Au NPs似乎并未影响甚至还刺激了干酪乳杆菌在人肠道上皮细胞中的免疫调节特性。因此，处于低抑菌水平的医学相关NPs会影响有益人类细菌的代谢，并可能引发微生物群和免疫信号的变化。
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