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Gray, M. J.

Publications and source records attributed to Gray, M. J..

2 recordsLinked to original sources

Complex responses to inflammatory oxidants by the probiotic bacterium Lactobacillus reuteri

Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of pro-inflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes. The pathways for H2O2 and HOCl resistance in E. coli have been well-studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms. These results raise the intriguing possibility of developing treatments for inflammatory gut diseases that could sensitize pro-inflammatory enterobacteria to killing by the immune system while sparing anti-inflammatory, health-associated species.\n\nIMPORTANCEIt is becoming increasingly clear that effective treatment of inflammatory gut diseases will require modulation of the gut microbiota. Preventing pro-inflammatory bacteria from blooming while also preserving anti-inflammatory and commensal species is a considerable challenge, but our results suggest that it may be possible to take advantage of differences in the way different species of gut bacteria resist inflammatory oxidants to accomplish this goal.

microbiology

Individual alpha frequency increases during a task but is unchanged by alpha-band flicker

Visual perception fluctuates in-synch with ongoing neural oscillations in the delta, theta, and alpha frequency bands of the human EEG. Supporting the relationship between alpha and perceptual sampling, recent work has demonstrated that variations in individual alpha frequency (IAF) correlate with the ability to discriminate one from two stimuli presented briefly in the same location. Other studies have found that after being presented with a flickering stimulus at alpha frequencies, perception of near-threshold stimuli fluctuates for a short time at the same frequency. Motivated by previous work, we were interested in whether this alpha entrainment involves shifts in IAF. While recording EEG, we tested whether two-flash discrimination (a behavioral correlate of IAF) can be influenced by [~]1s of rhythmic visual stimulation at two different alpha frequencies (8.3hz and 12.5hz). Speaking against the bottom-up malleability of IAF, we found no change in IAF during stimulation and no change in two-flash discrimination immediately afterwards. We also found synchronous activity that persisted after 12.5hz stimulation, which suggests that a separate source of alpha was entrained. Importantly, we replicated the correlation between IAF and two-flash discrimination in a no-stimulation condition, demonstrating the sensitivity of our behavioral measure. We additionally found that IAF increased during the task compared to rest, which demonstrates that IAF is influenced by top-down factors but is not involved in entrainment. In the framework of existing findings, we suggest that visual entrainment may involve ongoing perceptually-relevant oscillations from the delta to alpha frequency bands, serving to maintain rhythmic temporal expectations.

neuroscience