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Gut microbiome-metabonome interactions protect against liver injury
Saeedi B, Liu K, Owens J, et al. Gut-resident Lactobacilli activate hepatic Nrf2 and protect against oxidative liver injury. Cell Metabolism 2020; 315,: 956-968.e5.
Several strands of evidence support a role for the gut microbiome in influencing liver physiology and the host’s propensity to liver injury, although which specific bacteria may be implicated—and mechanistically how they crosstalk with the liver—remains poorly understood. In this study, researchers first performed a comparative transcriptomic and metabonomic analysis of liver tissue obtained from conventional mice and those that were germ-free (ie, sterile and lacking a gut microbiome). It was observed that only the conventional mice had hepatic transcripts of Nrf2 (nuclear factor erythroid 2–related factor 2), a transcription factor that is recognised as a master regulator of host antioxidant and xenobiotic responses. To explore further, researchers used a transgenic Nrf2 reporter Drosophila melanogaster screening assay, and identified that members of the bacterial genus Lactobacillus were capable of potently stimulating Nrf2 signalling. Furthermore, oral administration of the human commensal bacterium, Lactobacillus rhamnosus GG (LGG), to conventional mice resulted in potent hepatic Nrf2 activation and this was sufficient to protect against acute oxidative liver injury in two separate mouse models (paracetamol overdose and acute ethanol toxicity). Using tandem mass spectrometry to analyse portal blood from LGG-treated mice, researchers identified the presence of 5-methoxyindole acetic acid (5-MIAA). This is a small molecule produced by LGG and an activator of Nrf2. Collectively, these data delineate a novel specific mechanism by which the gut microbiome influences hepatic physiology, and where perturbation of the gut microbiome may increase vulnerability to liver injury.
Ileal organoids as a model system to study infection and replication of SARS-CoV-2 within human enterocytes
Lamers M, Beumer J, van der Vaart J et al . SARS-CoV-2 productively infects human gut enterocytes. Science 2020; eabc1669 (Online first) doi: 10.1126/science.abc1669.
Angiotensin-converting enzyme 2 (ACE2) is the receptor for both severe acute respiratory …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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