An engineered genetic circuit for lactose intolerance alleviation

Mingyue Cheng, Zhangyu Cheng, Yiyan Yu, Wangjie Liu, Ruihao Li, Zhenyi Guo, Jiyue Qin, Zhi Zeng, Lin Di, Yufeng Mo, Chunxiu Pan, Yuanhao Liang, Jinman Li, Yigang Tong, Yunjun Yan, Yi Zhan, Kang Ning

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND: Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis. RESULTS: Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of β-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and β-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. CONCLUSIONS: Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain β-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.

Original languageEnglish (US)
Pages (from-to)137
Number of pages1
JournalBMC Biology
Volume19
Issue number1
DOIs
StatePublished - Jul 5 2021
Externally publishedYes

Keywords

  • Genetic engineering
  • Gut microbiota
  • In vitro simulation
  • In vivo assessment
  • Lactose intolerance
  • Synthetic biology

ASJC Scopus subject areas

  • Biotechnology
  • Structural Biology
  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Plant Science
  • Developmental Biology
  • Cell Biology

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