1.
The Sleep-Immune Crosstalk in Health and Disease.
Besedovsky, L, Lange, T, Haack, M
Physiological reviews. 2019;99(3):1325-1380
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The interaction between sleep and immunity is an established phenomena. This thorough review article summarises sleep changes in response to both infectious and non-infectious immune system challenges and describes the role of sleep in supporting the immune system. Details are provided of how sleep affects the innate immune system (first line, rapid defence against infection) as well as the adaptive immune system (second line, delayed defence against infection), using a feedback system which promotes host defence. Sleep is associated with reduced infection risk and can improve infection outcome and vaccination responses. Sleep deprivation is also associated with chronic, low-grade inflammation. Nutrition Practitioners wishing to support immunity can focus on sleep as a simple lifestyle measure to enhance resilience.
Abstract
Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body's defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various immune parameters, is associated with a reduced infection risk, and can improve infection outcome and vaccination responses. The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade inflammation and is associated with various diseases that have an inflammatory component, like diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future research.
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Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.
Sorgdrager, FJH, Naudé, PJW, Kema, IP, Nollen, EA, Deyn, PP
Frontiers in immunology. 2019;10:2565
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Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.
Abstract
Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.
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Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.
Lach, G, Schellekens, H, Dinan, TG, Cryan, JF
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2018;15(1):36-59
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Hormones released in the gut can have an impact in the brain through a bidirectional relationship, known as the gut-brain axis. The release of these hormones may be controlled by the gut microbiota, however exact mechanisms are not fully understood. Most hormones originating in the gut may have a role in obesity development, which is often associated with psychiatric disorders. Understanding the relationship between gut microbiota and depression through gut derived signalling molecules may be of benefit and was the focus of this review. Diversity and stability of the gut microbiota is important for health, which is disrupted during depression and anxiety. The gut microbiota serves to produce brain, hormone and immune signals that can travel to the brain, and can be affected by poor gut health. For those with depression, side effects of anti-depressants can be a disruption of the gut microbiota, however how this impacts symptoms is not fully understood. It was concluded that although there is strong research on the gut microbiota and depression it is still in its infancy. The role of gut microbiota on signalling with the brain and the rest of the body seems to be important for depression and anxiety. This study could be used by healthcare professionals to understand how the gut microbiota can play a role in depression.
Abstract
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.