Recent data suggest that the human body is not such a neatly self-sufficient island after all. It is more like a super-complex ecosystem containing trillions of bacteria and other microorganisms that ...inhabit all our surfaces; skin, mouth, sexual organs, and specially intestines. It has recently become evident that such microbiota, specifically within the gut, can greatly influence many physiological parameters, including cognitive functions, such as learning, memory and decision making processes. Human microbiota is a diverse and dynamic ecosystem, which has evolved in a mutualistic relationship with its host. Ontogenetically, it is vertically inoculated from the mother during birth, established during the first year of life and during lifespan, horizontally transferred among relatives, mates or close community members. This micro-ecosystem serves the host by protecting it against pathogens, metabolizing complex lipids and polysaccharides that otherwise would be inaccessible nutrients, neutralizing drugs and carcinogens, modulating intestinal motility, and making visceral perception possible. It is now evident that the bidirectional signaling between the gastrointestinal tract and the brain, mainly through the vagus nerve, the so called "microbiota-gut-vagus-brain axis," is vital for maintaining homeostasis and it may be also involved in the etiology of several metabolic and mental dysfunctions/disorders. Here we review evidence on the ability of the gut microbiota to communicate with the brain and thus modulate behavior, and also elaborate on the ethological and cultural strategies of human and non-human primates to select, transfer and eliminate microorganisms for selecting the commensal profile.
The phenomenon of behaviorally conditioned immunological and neuroendocrine functions has been investigated for the past 100 yr. The observation that associative learning processes can modify ...peripheral immune functions was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. With the employment of a taste-avoidance paradigm in rats, this phenomenon was rediscovered 45 yr ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be modulated via associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provide fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.
•Cues associated with food trigger release of homeostasis regulating hormones.•Food anticipatory hormonal responses are consistently found in animals and humans.•These responses regulate hunger, ...prevent hypoglycemia, and improve metabolism.•Food anticipatory hormonal responses are largely learned phenomena.•Food anticipatory hormonal activity is impaired in eating and metabolic disorders.
Food anticipatory hormonal responses (cephalic responses) are proactive physiological processes, that allow animals to prepare for food ingestion by modulating their hormonal levels in response to food cues. This process is important for digesting food, metabolizing nutrients and maintaining glucose levels within homeostasis. In this systematic review, we summarize the evidence from animal and human research on cephalic responses. Thirty-six animal and fifty-three human studies were included. The majority (88 %) of studies demonstrated that hormonal levels are changed in response to cues previously associated with food intake, such as feeding time, smell, and sight of food. Most evidence comes from studies on insulin, ghrelin, pancreatic polypeptide, glucagon, and c-peptide. Moreover, impaired cephalic responses were found in disorders related to metabolism and food intake such as diabetes, pancreatic insufficiency, obesity, and eating disorders, which opens discussions about the etiological mechanisms of these disorders as well as on potential therapeutic opportunities.
Animals harbor an extensive, dynamic microbial ecosystem in their gut. Gut microbiota (GM) supposedly modulate various host functions including fecundity, metabolism, immunity, cognition and ...behavior. Starting by analyzing the concept of the holobiont as a unit of selection, we highlight recent findings suggesting an intimate link between GM and animal social behavior. We consider two reciprocal emerging themes: (i) that GM influence host social behavior; and (ii) that social behavior and social structure shape the composition of the GM across individuals. We propose that, throughout a long history of coevolution, GM may have become involved in the modulation of their host's sociality to foster their own transmission, while in turn social organization may have fine-tuned the transmission of beneficial endosymbionts and prevented pathogen infection. We suggest that investigating these reciprocal interactions can advance our understanding of sociality, from healthy and impaired social cognition to the evolution of specific social behaviors and societal structure.
The cross-cultural testing of scales represents an important step in the scale validation process. The present study evaluated whether the eight-item short version of the recently developed Food ...Disgust Scale (FDS-short) is a reliable and valid tool for measuring food disgust sensitivity in ten countries: Australia, China, England, France, Germany, Mexico, South Africa, Spain, Sweden, and the USA. In an online survey, the participants (N = 6128) answered items from the FDS-short and other scales related to (food) disgust sensitivity so as to test the construct and criterion validity of the FDS-short. Confirmatory factor analysis of the one-factor structure of the FDS-short revealed an adequate to good model fit in all the countries except for China. Multiple group analysis to test measurement invariance showed the FDS-short to be metrically invariant in all the tested countries (except for China) relative to Australia. With regard to the construct validity, significant positive correlations were observed in all the countries between the FDS-short and pathogen disgust sensitivity, sexual disgust sensitivity, moral disgust sensitivity, germ aversion, and food neophobia. Criterion validity of the FDS-short in all the tested countries was confirmed by the positive correlations between it and having a sensitive stomach, experiencing gastrointestinal complaints after eating animal-based foods (except for France and Germany), and the perceived infection risk of food-borne diseases in one's country. The direction of the correlations indicated that for each country, those with higher FDS-short scores also scored higher on all the tested constructs than those with lower FDS-short scores. Taken together, the present results indicate that the FDS-short is a reliable and valid tool for assessing food disgust sensitivity across countries.
The learned immune response: Pavlov and beyond Schedlowski, Manfred; Pacheco-López, Gustavo
Brain, behavior, and immunity,
02/2010, Letnik:
24, Številka:
2
Journal Article, Presentation
Recenzirano
Abstract The ability to associate physiological changes with a specific flavor was most likely acquired during evolution as an adaptive strategy aimed at protecting the organism while preparing it ...for danger. The behaviorally conditioned or learned immune response is an exquisite example of the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. How is it possible that specific immuno-modulating properties of a drug or substance (unconditioned stimulus) can be re-enlisted just by the mere re-exposure to a particular taste, odor or environment (conditioned stimulus)? To answer this key question, we review the neurobiological mechanism mediating this type of associative learning, as well as the pathways and mechanisms employed by the brain to harness the immune system during the execution of the conditioned immune response. Finally, we focus on the potential therapeutic relevance of such learned immune responses, and their re-conceptualization within the framework of “ learned placebo effects ”.
The irreversible and progressive neurodegenerative Alzheimer's disease (AD) is characterized by cognitive decline, extracellular β-amyloid peptide accumulation, and tau neurofibrillary tangles in the ...cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls non-transgenic mice (NoTg), at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.
Schizophrenia is associated with increased risk for multiple metabolic abnormalities, including altered glucose homeostasis, type-2 diabetes, obesity, and cardiovascular disease. Some of the ...metabolic alterations can already exist in psychosis-prone subjects prior to the onset of chronic schizophrenic disease and pharmacotherapy, indicating that they may have a developmental origin. In the present study, we tested the hypothesis that metabolic alterations pertinent to schizophrenic disease can be primed by an environmental risk factor associated with the disorder, namely prenatal exposure to immune challenge. We used a well-established mouse model of prenatal immune challenge induced by maternal gestational treatment with poly(I:C) (="polyriboinosinic-polyribocytidilic acid"), an analog of double-stranded RNA that stimulates a cytokine-associated viral-like acute phase response. Metabolic effects were studied using high-resolution computed tomography and fully automated indirect calorimetry system, along with an oral glucose tolerance test and plasma cytokine and corticosterone measurements. We found that prenatal immune activation caused altered glycemic regulation and abnormal ingestive behavior in periadolescence and led to an adult onset of excess visceral and subcutaneous fat deposition. These effects were accompanied by age-dependent changes in peripheral secretion of proinflammatory (interleukin IL-6 and tumor necrosis factor TNF-α) and T cell-related (IL-2 and interferon IFN-γ) cytokines and by increased release of the stress hormone corticosterone in periadolescence. Our findings show that schizophrenia-relevant metabolic and physiological abnormalities can be primed by prenatal viral-like immune activation, but at the same time, our study emphasizes that this environmental insult is unlikely to precipitate the full spectrum of metabolic and immunological changes pertinent to chronic schizophrenic disease.
Alzheimer’s disease (AD) is a multifactorial pathology characterized by β-amyloid (Aβ) deposits, Tau hyperphosphorylation, neuroinflammatory response, and cognitive deficit. Changes in the bacterial ...gut microbiota (BGM) have been reported as a possible etiological factor of AD. We assessed in offspring (F1) 3xTg, the effect of BGM dysbiosisdysbiosis in mothers (F0) at gestation and F1 from lactation up to the age of 5 months on Aβ and Tau levels in the hippocampus, as well as on spatial memory at the early symptomatic stage of AD. We found that BGM dysbiosisdysbiosis with antibiotics (Abx) treatment in F0 was vertically transferred to their F1 3xTg mice, as observed on postnatal day (PD) 30 and 150. On PD150, we observed a delay in spatial memory impairment and Aβ deposits, but not in Tau and pTau protein in the hippocampus at the early symptomatic stage of AD. These effects are correlated with relative abundance of bacteria and alpha diversity, and are specific to bacterial consortia. Our results suggest that this specific BGM could reduce neuroinflammatory responses related to cerebral amyloidosis and cognitive deficit and activate metabolic pathways associated with the biosynthesis of triggering or protective molecules for AD.
To address the neural mediation of the eating-inhibitory effect of circulating glucagon-like peptide-1 (GLP-1), we investigated the effects of 1) intra-fourth ventricular infusion of the GLP-1 ...receptor antagonist exendin-9 or 2) area postrema lesion on the eating-inhibitory effect of intrameal hepatic portal vein (HPV) GLP-1 infusion in adult male rats. To evaluate the physiological relevance of the observed effect we examined 3) the influence of GLP-1 on flavor acceptance in a 2-bottle conditioned flavor avoidance test, and 4) measured active GLP-1 in the HPV and vena cava (VC) in relation to a meal and in the VC after HPV GLP-1 infusion. Intrameal HPV GLP-1 infusion (1 nmol/kg body weight-5 min) specifically reduced ongoing meal size by almost 40% (P < .05). Intra-fourth ventricular exendin-9 (10 μg/rat) itself did not affect eating, but attenuated (P < .05) the satiating effect of HPV GLP-1. Area postrema lesion also blocked (P < .05) the eating-inhibitory effect of HPV GLP-1. Pairing consumption of flavored saccharin solutions with HPV GLP-1 infusion did not alter flavor acceptance, indicating that HPV GLP-1 can inhibit eating without inducing malaise. A regular chow meal transiently increased (P < .05) HPV, but not VC, plasma active GLP-1 levels, whereas HPV GLP-1 infusion caused a transient supraphysiological increase (P < .01) in VC GLP-1 concentration 3 minutes after infusion onset. The results implicate hindbrain GLP-1 receptors and the area postrema in the eating-inhibitory effect of circulating GLP-1, but question the physiological relevance of the eating-inhibitory effect of iv infused GLP-1 under our conditions.
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