An engineered genetic circuit for lactose intolerance alleviation.
BMC Biol
; 19(1): 137, 2021 07 05.
Article
em En
| MEDLINE
| ID: mdl-34225711
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 ß-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 ß-galactosidase activity and influence intestinal homeostasis.RESULTS:
Here, we synthesized a tri-stable-switch circuit equipped with high ß-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of ß-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 ß-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 ß-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Intolerância à Lactose
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article