Highlights d Changes in the gut microbiota are required for the antiseizure effects of the KD d S... more Highlights d Changes in the gut microbiota are required for the antiseizure effects of the KD d Specific KD-associated bacteria mediate and confer the anti-seizure effects of the KD d KD microbiota regulate amino acid g-glutamylation and hippocampal GABA/glutamate
The microbiota is increasingly recognized for its ability to influence the development and functi... more The microbiota is increasingly recognized for its ability to influence the development and function of the nervous system and several complex host behaviors. In this review, we discuss emerging roles for the gut microbiota in modulating host social and communicative behavior, stressorinduced behavior, and performance in learning and memory tasks. We summarize effects of the microbiota on host neurophysiology, including brain microstructure, gene expression, and neurochemical metabolism across regions of the amygdala, hippocampus, frontal cortex, and hypothalamus. We further assess evidence linking dysbiosis of the gut microbiota to neurobehavioral diseases, such as autism spectrum disorder and major depression, drawing upon findings from animal models and human trials. Finally, based on increasing associations between the microbiota, neurophysiology, and behavior, we consider whether investigating mechanisms underlying the microbiota-gut-brain axis could lead to novel approaches for treating particular neurological conditions.
Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggest... more Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggests that corticotropin-releasing factor (CRF) plays an important role in regulating the effects of stress. CRF administration produces stress-like effects in humans and laboratory animals, and CRF levels are elevated in individuals with stress-related illness. Recent work indicates that k-opioid receptor (KOR) antagonists can block CRF effects, raising the possibility that at least some of the effects of stress are mediated via KORs. Here we examined the effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT), a test used to quantify attention in rodents, as well as functional interactions between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and then each was implanted with an intracerebroventricular (ICV) cannula. After recovery and restabilization of performance, they received a single intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist with long-lasting (414 days) effects. In subsequent sessions, rats received ICV infusions of CRF (0.25-1.0 mg) or vehicle and were tested 60 min later. CRF dose-dependently disrupted performance as reflected by decreases in correct responding, increases in omission errors, increases in latencies to respond correctly, and increases in time to complete the session. JDTic attenuated each of these CRF-induced deficits while having no effects on its own. The persistent ability of JDTic to disrupt KOR function was confirmed using the tail immersion assay. These findings indicate that KOR antagonists can prevent acute stress-related effects that degrade performance in tasks requiring attention.
Parasitic nematode species often display highly specialized host-seeking behaviors that reflect t... more Parasitic nematode species often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many such behaviors are triggered by host odors, but little is known about either the specific olfactory cues that trigger these behaviors or the underlying neural circuits. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some devastating human-and plant-parasitic nematodes. We compare the olfactory responses of Heterorhabditis and Steinernema infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages . The broad host range of these parasites results from their ability to respond to the universally produced signal carbon dioxide (CO 2 ), as well as a wide array of odors, including host-specific odors that we identified using thermal desorption-gas chromatography-mass spectroscopy. We find that CO 2 is attractive for the parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults [2-4], and we identify a sensory neuron that mediates CO 2 response in both parasitic and free-living species, regardless of whether CO 2 is attractive or repulsive. The parasites' odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism.
Highlights d Gut microbes regulate levels of 5-HT in the colon and blood d Spore-forming bacteria... more Highlights d Gut microbes regulate levels of 5-HT in the colon and blood d Spore-forming bacteria modulate metabolites that promote colon 5-HT biosynthesis d Microbiota-dependent changes in 5-HT impact GI motility and hemostasis
Sleep is broadly conserved across the animal kingdom, but can vary widely between species. It is ... more Sleep is broadly conserved across the animal kingdom, but can vary widely between species. It is currently unclear which types of selective pressures and sleep regulatory mechanisms influence differences in sleep between species. The fruit flyDrosophila melanogasterhas become a successful model system for examining sleep regulation and function, but little is known about the sleep patterns and need for sleep in many related fly species. Here, we find thatDrosophila mojavensis, a fly species that has adapted to extreme desert environments, exhibits strong increases in sleep compared toD. melanogaster.Long-sleepingD. mojavensisshow intact sleep homeostasis, indicating that these flies carry an elevated need for sleep. In addition,D. mojavensisexhibit altered abundance or distribution of several sleep/wake related neuromodulators and neuropeptides that are consistent with their reduced locomotor activity, and increased sleep. Finally, we find that in a nutrient-deprived environment, th...
A Role for the Microbiota in Neurodevelopmental Disorders
The Gut-Brain Axis
Recent research into the complex interrelationship between the gastrointestinal and central nervo... more Recent research into the complex interrelationship between the gastrointestinal and central nervous systems has led to an increased appreciation of the importance of commensal gut microbes to normal gut function and neurobehavioral health. Epidemiological and clinical studies indicate co-morbid gut dysfunction in many individuals with psychiatric or neurodevelopmental disorders. Moreover, animal model studies present promising evidence that microbe-based treatments may alleviate symptoms of disease. Autism spectrum disorder is of particular interest as a highly prevalent neurodevelopmental disorder in which a significant subset of patients present with gastrointestinal problems and in which microbial dysbiosis has been highlighted as a potential contributing factor to gastrointestinal and neuropathological abnormalities. Preclinical studies investigating probiotic treatments for gastrointestinal, neurobiological, and behavioral deficits suggest that a richer understanding of the role of gut microbes in neurodevelopmental disorders may lead to effective new treatments.
Nematodes comprise a large phylum of both free-living and parasitic species that show remarkably ... more Nematodes comprise a large phylum of both free-living and parasitic species that show remarkably diverse lifestyles, ecological niches, and behavioral repertoires. Parasitic species in particular often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many host-seeking behaviors can be triggered by the presence of host odors, yet little is known about either the specific olfactory cues that trigger these behaviors or the neural circuits that underlie them. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some of the most devastating human- and plant-parasitic nematodes. Here we compare the olfactory responses of H. bacteriophora and S. carpocapsae infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages [1]. We show that the broad host range of these parasites results...
The microbiota is increasingly recognized for its ability to influence the development and functi... more The microbiota is increasingly recognized for its ability to influence the development and function of the nervous system and several complex host behaviors. In this review, we discuss emerging roles for the gut microbiota in modulating host social and communicative behavior, stressor-induced behavior, and performance in learning and memory tasks. We summarize effects of the microbiota on host neurophysiology, including brain microstructure, gene expression, and neurochemical metabolism across regions of the amygdala, hippocampus, frontal cortex, and hypothalamus. We further assess evidence linking dysbiosis of the gut microbiota to neurobehavioral diseases, such as autism spectrum disorder and major depression, drawing upon findings from animal models and human trials. Finally, based on increasing associations between the microbiota, neurophysiology, and behavior, we consider whether investigating mechanisms underlying the microbiota-gut-brain axis could lead to novel approaches fo...
The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5... more The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulator...
Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggest... more Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggests that corticotropin-releasing factor (CRF) plays an important role in regulating the effects of stress. CRF administration produces stress-like effects in humans and laboratory animals, and CRF levels are elevated in individuals with stress-related illness. Recent work indicates that k-opioid receptor (KOR) antagonists can block CRF effects, raising the possibility that at least some of the effects of stress are mediated via KORs. Here we examined the effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT), a test used to quantify attention in rodents, as well as functional interactions between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and then each was implanted with an intracerebroventricular (ICV) cannula. After recovery and restabilization of performance, they received a single intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist with long-lasting (414 days) effects. In subsequent sessions, rats received ICV infusions of CRF (0.25-1.0 mg) or vehicle and were tested 60 min later. CRF dose-dependently disrupted performance as reflected by decreases in correct responding, increases in omission errors, increases in latencies to respond correctly, and increases in time to complete the session. JDTic attenuated each of these CRF-induced deficits while having no effects on its own. The persistent ability of JDTic to disrupt KOR function was confirmed using the tail immersion assay. These findings indicate that KOR antagonists can prevent acute stress-related effects that degrade performance in tasks requiring attention.
Parasitic nematode species often display highly specialized host-seeking behaviors that reflect t... more Parasitic nematode species often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many such behaviors are triggered by host odors, but little is known about either the specific olfactory cues that trigger these behaviors or the underlying neural circuits. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some devastating human-and plant-parasitic nematodes. We compare the olfactory responses of Heterorhabditis and Steinernema infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages . The broad host range of these parasites results from their ability to respond to the universally produced signal carbon dioxide (CO 2 ), as well as a wide array of odors, including host-specific odors that we identified using thermal desorption-gas chromatography-mass spectroscopy. We find that CO 2 is attractive for the parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults [2-4], and we identify a sensory neuron that mediates CO 2 response in both parasitic and free-living species, regardless of whether CO 2 is attractive or repulsive. The parasites' odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism.
Highlights d Changes in the gut microbiota are required for the antiseizure effects of the KD d S... more Highlights d Changes in the gut microbiota are required for the antiseizure effects of the KD d Specific KD-associated bacteria mediate and confer the anti-seizure effects of the KD d KD microbiota regulate amino acid g-glutamylation and hippocampal GABA/glutamate
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Papers by Jessica Yano