Safety and Modulatory Effects of Humanized Galacto-Oligosaccharides on the Gut Microbiome.
Safety and Modulatory Effects of Humanized Galacto-Oligosaccharides on the Gut Microbiome.
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DOI：
10.3389/fnut.2021.640100
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发表时间：
2021
影响因子：
5
通讯作者：
Bruno-Barcena JM
中科院分区：
文献类型：
--
作者：
Arnold JW;Whittington HD;Dagher SF;Roach J;Azcarate-Peril MA;Bruno-Barcena JM
包括β（1-4）低聚半乳糖（GOS）的复杂膳食碳水化合物结构在上消化道（GI）中抵抗消化，并完整地到达结肠，在结肠中它们通过选择性地刺激微生物生长而有益于宿主。研究报告了GOS（单独或与其他益生元组合）的有益影响，即作为代谢底物调节婴儿肠道微生物组的组装，同时减少GI感染。N-乙酰-D-乳糖胺（LacNAc，Galβ1，4GlcNAc）是母乳中的一种游离二糖。这种化合物也被发现是人乳低聚糖（HMO）的一种组分，其具有重复和支链乳糖和/或LacNAc单元，通常与唾液酸和岩藻糖单糖连接。人类糖基水解酶不会降解大多数HMO，这表明这些结构已经进化为天然益生元，以驱动婴儿健康肠道微生物群的正确组装。在这里，我们试图开发一种新的酶促方法，用于产生富含LacNAc的GOS，我们称之为人源化GOS（hGOS）。我们发现来自Hamamotoa（Sporobolomyces）singularis的膜结合β-己糖基转移酶（rBHT）能够从乳糖和N-乙酰氨基葡萄糖（GlcNAc）产生GOS和hGOS。该酶催化半乳糖从乳糖到GlcNAc的区域选择性重复加成，在GlcNAc的4位和D-半乳糖的1位形成β-半乳糖基键，除了GOS之外，还产生LacNAc和半乳糖基-LacNAc三聚体，它们是通过两次连续的转半乳糖基化产生的。人源化GOS在化学上与HMO不同，其在体内的作用尚未确定。因此，我们评估了它的安全性，并证明了益生元调节6周龄C57 BL/6 J小鼠肠道微生物组的能力。从喂食含有hGOS的饮食5周的小鼠收集的粪便样品的肠道微生物组组成的纵向分析显示α多样性的短暂减少。与对照喂养的动物相比，在hGOS和GOS之间观察到主要在厚壁菌门内的微生物群落组成的差异。总之，我们的研究证明了hGOS的生物合成，并表明其安全性和调节体内肠道微生物组的能力，促进有益微生物的生长，包括双歧杆菌和阿克曼氏菌。
Complex dietary carbohydrate structures including β(1–4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract and arrive intact to the colon where they benefit the host by selectively stimulating microbial growth. Studies have reported the beneficial impact of GOS (alone or in combination with other prebiotics) by serving as metabolic substrates for modulating the assembly of the infant gut microbiome while reducing GI infections. N-Acetyl-D-lactosamine (LacNAc, Galβ1,4GlcNAc) is found in breast milk as a free disaccharide. This compound is also found as a component of human milk oligosaccharides (HMOs), which have repeating and variably branched lactose and/or LacNAc units, often attached to sialic acid and fucose monosaccharides. Human glycosyl-hydrolases do not degrade most HMOs, indicating that these structures have evolved as natural prebiotics to drive the proper assembly of the infant healthy gut microbiota. Here, we sought to develop a novel enzymatic method for generating LacNAc-enriched GOS, which we refer to as humanized GOS (hGOS). We showed that the membrane-bound β-hexosyl transferase (rBHT) from Hamamotoa (Sporobolomyces) singularis was able to generate GOS and hGOS from lactose and N-Acetyl-glucosamine (GlcNAc). The enzyme catalyzed the regio-selective, repeated addition of galactose from lactose to GlcNAc forming the β-galactosyl linkage at the 4-position of the GlcNAc and at the 1-position of D-galactose generating, in addition to GOS, LacNAc, and Galactosyl-LacNAc trisaccharides which were produced by two sequential transgalactosylations. Humanized GOS is chemically distinct from HMOs, and its effects in vivo have yet to be determined. Thus, we evaluated its safety and demonstrated the prebiotic's ability to modulate the gut microbiome in 6-week-old C57BL/6J mice. Longitudinal analysis of gut microbiome composition of stool samples collected from mice fed a diet containing hGOS for 5 weeks showed a transient reduction in alpha diversity. Differences in microbiome community composition mostly within the Firmicutes phylum were observed between hGOS and GOS, compared to control-fed animals. In sum, our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo, promoting the growth of beneficial microorganisms, including Bifidobacterium and Akkermansia.
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影响因子：
4.1
作者：
Balogh, Reka;Jankovics, Peter;Beni, Szabolcs
通讯作者：
Beni, Szabolcs
保加利亚乳杆菌和植物乳杆菌产生的新型低聚糖的结构鉴定
影响因子：
6.1
作者：
Black, Brenna A.;Lee, Vivian S. Y.;Gaenzle, Michael G.
通讯作者：
Gaenzle, Michael G.
影响因子：
4.2
作者：
Allali I;Arnold JW;Roach J;Cadenas MB;Butz N;Hassan HM;Koci M;Ballou A;Mendoza M;Ali R;Azcarate-Peril MA
通讯作者：
Azcarate-Peril MA
DOI：
10.1097/00005176-198302030-00018
发表时间：
1983-01-01
影响因子：
2.9
作者：
DEWEY, KG;LONNERDAL, B
通讯作者：
LONNERDAL, B
影响因子：
6.1
作者：
Arreola, Sheryl Lozel;Intanon, Montira;Thu-Ha Nguyen
通讯作者：
Thu-Ha Nguyen