Lactobacillus GG Modulates Epithelial Cytoprotection through the Nrf2 Pathway

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The idea that bacteria in the gut may have many twists in their skill set to enhance human health has been around for a while. That they may have the capability of inducing a cytoprotective enzyme called Nrf2 in local tissues, which in turn promotes the production of glutathione, detoxification and numerous other health supportive elements has until recently been less well understood.[1]

Nrf2 activation upregulates a regulon of genes including those involved in xenobiotic and reactive oxygen species (ROS) detoxification, as well as pro-restitutive function. This pathway has attracted considerable attention because small molecule inducers of Nrf2 have cytoprotective effects against oxidant and electrophilic environmental stressors.[2],[3]

I have previously discussed this cytoprotective switch as the use of nutrient concentrates to induce a mild oxidative stress to this defence molecule results in a positive secondary response, and may account for some of the human health benefits derived from a traditional Mediterranean and Okinawan diet.[4]

The paper by Jones and colleagues published in Cell Reports explore this cytoprotective mechanism through their investigation in the role of lactic acid bacteria in the gut. Using Lactobacillus GG a very well-studied human species of bacteria in a mouse model demonstrated clear up regulation of key cytochrome P450 enzymes and so aid local cell detoxification via mutual interactions and help explain the role of this probiotic in assisting in the reduction of radiation damage in the gut.[5]

The researcher state: Thus, members of the genus lactobacilli may have evolved symbiotic relationships where microbial-induced generation of ROS functions as a transducer of bacterial signals into host gene regulatory events that potentiate multiple effects in disparate biological systems. We describe a molecular mechanism by which lactobacilli can elicit their beneficial influences on host gut tissues, wherein ROS generated by Nox following bacterial contact activates downstream cytoprotective signalling.

They also note that effects appear to be species an strain specific, and whilst the paper does not explore human cell responses the implication is that the use of a single strain of probiotic may need to be looked at beyond immune and metabolic interactions and include cytoprotective induction, and if this is the case it helps to explain why benefits of bacterial ingestion have evolved with humans over millennia to assist with multiple health benefits and risk management.

Taken together, these observations are consistent with the concept of “hormesis,” wherein low, near threshold levels of a stressor is protective against more intense or prolonged stimuli. Making the statement “that which does not kill you makes you stronger” by Friedrich Nietzsche even relevant at a molecular and bacterial level.



[1] Jones RM, Desai C, Darby TM, Luo L, Wolfarth AA, Scharer CD, Ardita CS, Reedy AR, Keebaugh ES, Neish. Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway. Cell Rep. 2015 Aug 12. pii: S2211-1247(15)00802-5. View Full Paper

[2] Mukaigasa K, Nguyen LT, Li L, Nakajima H, Yamamoto M, Kobayashi M. Genetic evidence of an evolutionarily conserved role for Nrf2 in the protection against oxidative stress. Mol Cell Biol. 2012 Nov;32(21):4455-61. View Full Paper

[3] Ma Q, He X. Molecular basis of electrophilic and oxidative defense: promises and perils of Nrf2. Pharmacol Rev. 2012 Oct;64(4):1055-81 View Full Paper

[4] Pall ML, Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao. 2015 Feb 25;67(1):1-18. View Full Paper

[5] Ciorba MA, Riehl TE, Rao MS, Moon C, Ee X, Nava GM, Walker MR, Marinshaw JM, Stappenbeck TS, Stenson WF. Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner. Gut. 2012 Jun;61(6):829-38. View Full Paper

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In this article:

Culturelle, Cytoprotective, Detoxification, LGG, Microbiota, NrF2