Protection of gut microbiome from antibiotics: development of a vancomycin-specific adsorbent with high adsorption capacity

Kazuki Yuzuriha; Kyosuke Yakabe; Haruka Nagai; Shunyi Li; Takeshi Zendo; Khadijah Zai; Akihiro Kishimura; Koji Hase; Yun-Gi Kim; Takeshi Mori; Yoshiki Katayama

doi:10.12938/bmfh.2020-002

Protection of gut microbiome from antibiotics: development of a vancomycin-specific adsorbent with high adsorption capacity

Biosci Microbiota Food Health. 2020;39(3):128-136. doi: 10.12938/bmfh.2020-002. Epub 2020 Feb 29.

Authors

Kazuki Yuzuriha¹, Kyosuke Yakabe^{2

3}, Haruka Nagai¹, Shunyi Li¹, Takeshi Zendo⁴, Khadijah Zai⁵, Akihiro Kishimura^{1

6

7

8}, Koji Hase^{2

9}, Yun-Gi Kim³, Takeshi Mori^{1

6

7}, Yoshiki Katayama^{1

6

7

8

10

11}

Affiliations

¹ Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
² Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
³ Research Center for Drug Discovery, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
⁴ Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 819-039, Japan.
⁵ Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia.
⁶ Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
⁷ Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
⁸ International Research Center for Molecular Systems, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
⁹ Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
¹⁰ Advanced Medicine Innovation Center, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
¹¹ Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Rd., Chung Li, 32023 ROC, Taiwan.

Abstract

The fraction of administered antibiotics that reach the cecum and colon causes dysbiosis of the gut microbiome, resulting in various diseases. Protection of the gut microbiome from antibiotics using antibiotic adsorbents in the cecum and colon is a promising method to overcome this issue. Previously, activated charcoal (AC) has been reported to protect the gut microbiome of host animals. AC is an adsorbent that is widely used to capture toxic compounds and overdosed drugs in the gastrointestinal tract. The specificity of adsorbents for antibiotics is critical to avoid the risk of unexpected side effects caused by nonspecific adsorption of biological compounds in the intestinal fluid, such as bile acids and essential micronutrients. Here, we have developed specific adsorbents for vancomycin (VCM), which is known to cause gut dysbiosis. The adsorbents were composed of polyethyleneglycol-based microparticles (MPs) in which a specific ligand for VCM, D-Ala-D-Ala-OH, was attached via dendrons of D-lysine to raise the content of the ligand in the MPs. The MPs successfully protected Staphylococcus lentus from VCM in vitro because of the adsorption of VCM in the culture media. Pre-administration of MPs to mice reduced the amount of free VCM in the feces to an undetectable level. This treatment minimized the effect of VCM on gut microbiota and provided protection against Clostridioides difficile infection after oral challenge with spores.

Keywords: adsorbent; antibiotic; dysbiosis; microbiome; microparticle.