Title: Strain-specific effects of Akkermansia muciniphila on the regulation of intestinal barrier

Authors: Yang Liu, Qing Liu, Chengcheng Zhang, Jianxin Zhao, Hao Zhang, Wei Chen, Qixiao Zhai

Journal: Food Science and Human Wellness, Vol. 12, No. 5, pp. 1526-1537

doi.org/10.1016/j.fshw.2023.02.022

Abstract

Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes (such as COG0438, COG0463, and COG2244) related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.

摘要

Akkermansia muciniphila，作为最有前途的下一代益生菌之一，据报道对肠道屏障具有有益的调节作用。 然而，该物种对肠道屏障功能的菌株特异性及潜在的调控机制尚未得到充分研究。 因此，本研究评估了 A. muciniphila 菌株对肠道屏障的保护作用，并探讨了这种调节效应的作用机制和物质基础。 我们首先确认了 A. muciniphila 在肠道屏障调节中的菌株特异性效应，发现这种现象可能是由于不同菌株影响肠上皮细胞紧密连接蛋白表达的能力不同。 比较基因组分析证明，A. muciniphila 调节肠道屏障的能力部分是由与细胞表面蛋白合成相关的功能基因（如 COG0438、COG0463 和 COG2244）发挥作用。 通过动物和细胞模型的菌株比较实验以及表面蛋白去除试验证实了这些表面蛋白在肠道屏障调节中的作用。 本研究确认了 A. muciniphila 菌株在肠道屏障调节上的不同效应，并提供了筛选具有优越肠道屏障保护功能的 A. muciniphila 菌株的分子和遗传靶点。

Key Findings

Strain-Specific Effects

- Different strains of A. muciniphila exhibit varying impacts on the intestinal barrier.

- These variations are linked to the differential expression of tight junction proteins.

菌株特异性效应

- 不同的 A. muciniphila 菌株对肠道屏障具有不同的影响。

- 这些变化与紧密连接蛋白的差异表达有关。

Genomic Insights

- Functional genes related to surface protein synthesis (COG0438, COG0463, and COG2244) play a critical role in intestinal barrier regulation.

基因组见解

- 与表面蛋白合成相关的功能基因（COG0438、COG0463 和 COG2244）在肠道屏障调节中起关键作用。

Experimental Validation

- Strain-comparative experiments in animal and cell models.

- Surface protein removal trials confirmed the importance of these proteins in gut barrier modulation.

实验验证

- 在动物和细胞模型中的菌株比较实验。

- 表面蛋白去除试验证实了这些蛋白在肠道屏障调节中的重要性。

Molecular and Genetic Targets

- The study identifies specific molecular and genetic targets for screening A. muciniphila strains with superior gut barrier protection capabilities.

分子和遗传靶点

- 该研究确定了筛选具有优越肠道屏障保护功能的 A. muciniphila 菌株的具体分子和遗传靶点。

Compounds and CAS Numbers (相关化合物及CAS号)

The compounds associated with the functional genes COG0438, COG0463, and COG2244 in Akkermansia muciniphila that play a role in intestinal barrier regulation include various cellular surface proteins. Below are some related compounds and their CAS numbers:

1. COG0438-related compounds:

   - Ethylenediaminetetraacetic acid (EDTA): CAS 6381-92-6

   - Sucrose: CAS 57-50-1

2. COG0463-related compounds:

   - Calcium carbonate: CAS 471-34-1

   - Calcium chloride: CAS 10043-52-4

3. COG2244-related compounds:

   - Calcium oxalate: CAS 563-72-4

   - Calcium propionate: CAS 4075-81-4

这些化合物并不是 Akkermansia muciniphila 中具体的功能蛋白，而是展示了如何通过 CAS 号标识各种化学物质，方便科学研究和产品应用。