The Gut Microbiota and their Metabolites:Potential Implications for the Host Epigenome

The gut microbiota represents a metabolically active biomass of up to 2 kg in adult humans. Microbiota-derived molecules significantly contribute to the host metabolism. Large amounts of bacterial metabolites are taken up by the host and are subsequently utilized by the human body. For instance, short chain fatty acids produced by the gut microbiota are a major energy source of humans.It is widely accepted that microbiota-derived metabolites are used as fuel for beta-oxidation (short chain fatty acids) and participate in many metabolic processes (vitamins, such as folic acid). Apart from these direct metabolic effects, it also becomes more and more evident that these metabolites can interact with the mammalian epigenetic machinery. By interacting with histones and DNA they may be able to manipulate the host's chromatin state and functionality and hence its physiology and health.In this chapter, we summarize the current knowledge on possible interactions of different bacterial metabolites with the mammalian epigenetic machinery, mostly based on in vitro data. We discuss the putative impact on chromatin marks, for example histone modifications and DNA methylation. Subsequently, we speculate about possible beneficial and adverse consequences for the epigenome, the physiology and health of the host, as well as plausible future applications of this knowledge for in vivo translation to support personal health.</p

DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy

Funding Information: This material is based upon work supported by the US Department of Energy, Office of Science, Office of Fusion Energy Sciences, using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-FC02-04ER54698 and DE-AC52-07NA27344. Publisher Copyright: © 2022 IAEA, Vienna.DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.Peer reviewe