Editors' ChoiceHost-Microbe Interactions

Protection between tissues and across species

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Science Signaling  26 May 2020:
Vol. 13, Issue 633, eabb7040
DOI: 10.1126/scisignal.abb7040

Lactobacilli in the gut stimulate Nrf2-dependent antioxidant responses in the liver.

Blood flow from the intestine to the liver through the hepatic portal vein ensures that the liver receives signals produced by the intestinal microbiome. Saeedi et al. found that switching mice initially raised in a germ-free environment to a conventional environment was associated with increased hepatic expression of gene targets of Nrf2, a transcription factor that mediates antioxidant responses. Drosophila fed various Lactobacilli species showed Nrf2 activity in the fat body, an organ analogous to the liver. Feeding of the human commensal Lactobacillus rhamnosus GG improved survival in Drosophila given acetaminophen or paraquat, both of which induce oxidative stress. Similarly, oral gavage of mice with L. rhamnosus GG stimulated hepatic Nrf2 activity and conferred protection from acetaminophen and ethanol hepatotoxicity in an Nrf2-dependent manner. The small molecule 5-methoxyindoleacetic acid (5-MIAA) was present in the portal blood of mice given L. rhamnosus GG. Application of 5-MIAA to HepG2 cells increased the expression of Nrf2 target genes and promoted the nuclear translocation and activation of Nrf2. Thus, Lactobacilli in the gut stimulate Nrf2 in the liver to protect this organ from oxidative stress.

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