A microbiome-dependent gut–brain pathway regulates motivation for exercise

Dohnalová, Lenka; Lundgren, Patrick; Carty, Jamie R. E.; Goldstein, Nitsan; Wenski, Sebastian L; Nanudorn, Pakjira; Thiengmag, Sirinthra; Huang, Kuei-Pin; Litichevskiy, Lev; Descamps, Hélène C.; Chellappa, Karthikeyani; Glassman, Ana; Kessler, Susanne; Kim, Jihee; Cox, Timothy; Dmitrieva-Posocco, Oxana; Wong, Andrea C.; Allman, Erik; Ghosh, Soumita; Sharma, Nitika; Sengupta, Kasturi; Cornes, Belinda K.; Dean, Nitai; Churchill, Gary A.; Khurana, Tejvir S.; Sellmyer, Mark A.; FitzGerald, Garret A.; Patterson, Andrew D.; Baur, Joseph A.; Alhadeff, Amber L.; Helfrich, Eric J. N.; Levy, Maayan; Betley, J. Nicholas; Thaiss, Christoph A.

doi:10.1038/s41586-022-05525-z

Cited by 141 publications

(98 citation statements)

References 34 publications

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“…In this view, persistently lower levels of argininosuccinate and 5‐methylthioadenosine may reflect alterations to nitrogen homeostasis resulting from nitric oxide production to stimulate vasodilation, 45,46 as well as mediate ongoing purine salvage in red blood cells, which is also modulated by oxidative stress 47,48 . Finally, higher levels of indole‐5,6‐quinone may indicate an involvement of gut microbiota, which has been increasingly appreciated to contribute to sport performance 49 as well as motivation to exercise 50 . While speculative, future studies will be required to disentangle the mechanisms underlying these persistent metabolic changes after running.…”

Section: Resultsmentioning

confidence: 99%

Dried blood spot characterization of sex‐based metabolic responses to acute running exercise

Cendali

D’Alessandro

Nemkov

2023

Analytical Science Advances

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Metabolomics and lipidomics techniques are capable of comprehensively measuring hundreds to thousands of small molecules in single analytical runs and have been used to characterize responses to exercise traditionally using venipuncture‐produced liquid samples. Advanced microsampling devices offer an alternative by circumventing the requirement to maintain frozen samples. This approach combines a microneedle puncture for blood draw with microfluidic sample collection onto a dried carrier and has thus far been employed for targeted measurements of a few analytes. To demonstrate the utility of advanced dried microsampling to characterize metabolomic and lipidomic changes during exercise, we obtained samples before and after a 2‐mile run from twelve (8 male, 4 female) healthy volunteers with various ranges in activity levels. Results highlighted significant changes in whole blood levels of several metabolites associated with energy (glycolysis and Tricarboxylic Acid cycle) and redox (Pentose Phosphate Pathway) metabolism. Lipid changes during this same period were individualized and less uniform. Sex‐based differences in response to running highlighted reliance on carbohydrate or fat substrate utilization in males or females, respectively. The results presented herein illustrate the ability of this approach to monitor circulating metabolome and lipidome profiles from field sampled blood in response to exercise.

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Section: Resultsmentioning

confidence: 99%

Dried blood spot characterization of sex‐based metabolic responses to acute running exercise

Cendali

D’Alessandro

Nemkov

2023

Analytical Science Advances

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“…The essential role of this pathway in running motivation was shown by the finding that microbiome depletion as well as peripheral CB1 receptor antagonism, ablation of spinal afferent neurons, or dopamine blockade, all impaired exercise capacity. 10 …”

Section: The Gμbiome–ecbome Axis In Peripheral Inflammation and Brain...mentioning

confidence: 99%

The Gut Microbiome–Endocannabinoidome Axis: A New Way of Controlling Metabolism, Inflammation, and Behavior

Silvestri

Marzo

2023

Function

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“…These may include neuronal pathways related to enteroendocrine sensing of metabolites, interoceptive signals, and homeostatic reflex loops to regulate GI motility, blood flow, and secretion (Porreca et al, 2002;Mayer and Tillisch, 2011;Carabotti et al, 2015;Mayer et al, 2022), and a direct synapse to vagal neurons through neuropod cells (Kaelberer et al, 2018). A relevant new research area within sensory neurobiology has emerged, namely the field of gut-brain sensory transduction of stimuli for the brain to guide behavior, such as exercise (Kaelberer et al, 2020;Dohnalová et al, 2022). The enteroendocrine cells of the gut produce >90% of the body's total serotonin (5-hydroxytryptamine), which is an important regulator of secretion and motility of the gastro-intestinal tract (Kim and Camilleri, 2000).…”

Section: Modeling the Gut-brain Axismentioning

confidence: 99%

Getting closer to modeling the gut-brain axis using induced pluripotent stem cells

Hall

Bendtsen

2023

Front. Cell Dev. Biol.

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The gut microbiome (GM), the gut barrier, and the blood-brain barrier (BBB) are key elements of the gut-brain axis (GBA). The advances in organ-on-a-chip and induced pluripotent stem cell (iPSCs) technology might enable more physiological gut-brain-axis-on-a-chip models. The ability to mimic complex physiological functions of the GBA is needed in basic mechanistic research as well as disease research of psychiatric, neurodevelopmental, functional, and neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. These brain disorders have been associated with GM dysbiosis, which may affect the brain via the GBA. Although animal models have paved the way for the breakthroughs and progression in the understanding of the GBA, the fundamental questions of exactly when, how, and why still remain unanswered. The research of the complex GBA have relied on equally complex animal models, but today’s ethical knowledge and responsibilities demand interdisciplinary development of non-animal models to study such systems. In this review we briefly describe the gut barrier and BBB, provide an overview of current cell models, and discuss the use of iPSCs in these GBA elements. We highlight the perspectives of producing GBA chips using iPSCs and the challenges that remain in the field.

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A microbiome-dependent gut–brain pathway regulates motivation for exercise

Cited by 141 publications

References 34 publications

Dried blood spot characterization of sex‐based metabolic responses to acute running exercise

Dried blood spot characterization of sex‐based metabolic responses to acute running exercise

The Gut Microbiome–Endocannabinoidome Axis: A New Way of Controlling Metabolism, Inflammation, and Behavior

Getting closer to modeling the gut-brain axis using induced pluripotent stem cells

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