Certain types of intestinal bacteria can help protect the liver from injuries such as alcohol or acetaminophen overdose, according to Emory scientists led by pathologist Andrew Neish and physiologist Dean Jones.
The research was published on March 25 in Cell Metabolism.
“The composition of the microbiota, because of natural variation, dysbiosis, or supplementation with probiotics, can strongly affect how the liver processes both toxins and pharmacological agents, and thus have clinical consequences on how individuals respond to such exogenous chemicals,” Neish says.
While pretreatment with bacteria is needed for the observed effect in acute liver injury, probiotics or small molecule substitutes may be useful in the treatment of chronic liver diseases, the authors suggest.
In mice, oral administration of Lactobacillus rhamnosus or LGG could protect against liver damage brought on by alcohol or acetaminophen. Several labs had already observed a beneficial effect from LGG against liver injury, but the Emory research establishes an additional mechanism.
The protection comes from a small molecule metabolite produced by the bacteria called 5-MIAA (5-methoxyindoleacetic acid), activating the mammalian transcription factor Nrf2. Other types of bacteria did not produce 5-MIAA or activate Nrf2. While LGG is also known to improve the barrier function of the gut and dampen inflammation, liver-specific depletion of Nrf2 prevented LGG’s beneficial effects, suggesting that this is the primary mechanism of action. Read more
This recent paper in Circulation, from Arshed Quyyumi and colleagues at the Emory Clinical Cardiovascular Research Institute, can be seen as a culmination of, even vindication for, Â Dean Jones’ ideasÂ about redox biology.
Let’s back up a bit.Â Fruit juices, herbal teas, yogurts, even cookies are advertised as containing antioxidants, whichÂ could potentiallyÂ fight aging. This goes back to Denham Harman and the free radical theory of aging.Â [I attemptedÂ to explain this several years ago in Emory Medicine.]
We now know that free radicals, in the form of reactive oxygen species, can sometimes be good, even essential for life. So antioxidants that soak up free radicals to relieve you of oxidative stress: that doesn’t seem to work.
Dean Jones, who is director of Emory’s Clinical Biomarkers laboratory,Â has been an advocate for a different way of looking at oxidative stress. That is, instead of seeing cells asÂ big bags of redox-sensitive chemicals, look at cellular compartments. Look at particular antioxidant proteins and sulfur-containing antioxidant molecules such asÂ glutathione and cysteine.
That’s what theÂ Circulation paper does. Mining the Emory Cardiovascular Biobank, Quyyumi’s team shows that patients with coronary artery disease have a risk of mortality that is connected to the ratio of glutathione to cystine (the oxidized form of the amino acid cysteine).
How this ratio might fit in with other biomarkers of cardiovascular risk (such as CRP, suPAR, PCSK9,Â more complicated combinationsÂ and gene expression profiles, even more links here) and be implemented clinically areÂ still unfolding.
Derek Lowe, a respected science blogger and drug discovery expert who was blogging when this writer was still working in the laboratory, today has a roundup of a concept that anyone hanging around Emory might have clued into already.
Namely, antioxidants arenâ€™t all theyâ€™re cracked up to be. Judging from the messages Gafas Ray Ban outlet to shoppers in the supermarket vitamin aisle, everybody needs more antioxidants. But evidence is accumulating that in some situations, antioxidants can be harmful: negating the adaptive effects of exercise on muscle tissue or even encouraging tumor growth, Lowe writes.
At Emory, Dean Jones has been patiently explaining for years that cells are not simply big bags with free radicals, thiols and antioxidants sloshing around indiscriminately. Instead, cells and oxidation-sensitive components are highly compartmentalized. Take for example, this recent paper in Molecular & Cellular Proteomics from Jones and Young-mi Go. Two major antioxidant systems in cells, glutathione and thioredoxin, function distinctly and independently, they show.
In a related vein, Kathy Griendlingâ€™s and David Lambethâ€™s labs were at the center of the discovery that reactive oxygen species are not only poisons that overflow from mitochondria, but important signals involved in many aspects of cell biology.