通过增加透明质酸的生物合成来增强自封装益生菌嗜热链球菌的稳定性和功能,ACS Applied Materials & Interfaces

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通过增加透明质酸的生物合成来增强自封装益生菌嗜热链球菌的稳定性和功能
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-09-15 , DOI: 10.1021/acsami.2c11591
Dong-Xu Ma ₁ , Ying Zhou ₁ , Li-Dan Wu ₁ , Zu-Yi Li ₁ , Wen-Jie Jiang _{1,

2} , Si-Ling Huang ₃ , Xue-Ping Guo ₃ , Ju-Zheng Sheng _{1,

2} , Feng-Shan Wang _{1,

2}

Affiliation

胃肠道的恶劣条件限制了口服益生菌的潜在健康益处。通过加强益生菌的自我保护来提高口服生物利用度是有希望的。在这里，我们报告了通过内源性生产透明质酸来封装益生菌菌株，以增强菌株口服给药的效果。传统的益生菌嗜热链球菌被设计为通过使用无痕基因修饰和聚集的规则间隔短回文重复干扰来产生透明质酸壳。以发酵乳的形式口服给小鼠后，涂有透明质酸的嗜热链球菌（牛奶中含有 204.45 mg/L 透明质酸）与野生型菌株相比，在肠道中表现出更高的存活率和更长的定植时间。特别是，工程益生菌菌株还可以在肠道定植后产生透明质酸。重要的是，用透明质酸自包裹的嗜热链球菌增加了杯状细胞的数量、粘液的产生和与短链脂肪酸生物合成相关的微生物的丰度，从而增强了肠道屏障。内源性透明质酸形成的涂层为益生菌的有效口服给药提供了理想的参考。

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Enhanced Stability and Function of Probiotic Streptococcus thermophilus with Self-Encapsulation by Increasing the Biosynthesis of Hyaluronan

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the self-protection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

更新日期：2022-09-15

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