1.
Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism.
Choi, H, Rao, MC, Chang, EB
Nature reviews. Gastroenterology & hepatology. 2021;(10):679-689
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Abstract
Certain members of the gut microbiota exhibit diurnal variations in relative abundance and function to serve as non-canonical drivers of host circadian rhythms and metabolism. Also known as microbial oscillators, these microorganisms entrain upon non-photic cues, primarily dietary, to modulate host metabolism by providing input to both circadian clock-dependent and clock-independent host networks. Microbial oscillators are generally promoted by plant-based, low-fat (lean) diets, and most are abolished by low-fibre, high-sugar, high-fat (Western) diets. The changes in microbial oscillators under different diets then affect host metabolism by altering central and peripheral host circadian clock functions and/or by directly affecting other metabolic targets. Here, we review the unique role of the gut microbiota as a non-photic regulator of host circadian rhythms and metabolism. We describe genetic, environmental, dietary and other host factors such as sex and gut immunity that determine the composition and behaviour of microbial oscillators. The mechanisms by which these oscillators regulate host circadian gene expression and metabolic state are further discussed. Because of the gut microbiota's unique role as a non-photic driver of host metabolism and circadian rhythms, the development and clinical application of novel gut microbiota-related diagnostics and therapeutics hold great promise for achieving and maintaining metabolic health.
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Circadian Host-Microbiome Interactions in Immunity.
Butler, TD, Gibbs, JE
Frontiers in immunology. 2020;:1783
Abstract
The gut microbiome plays a critical role in regulating host immunity and can no longer be regarded as a bystander in human health and disease. In recent years, circadian (24 h) oscillations have been identified in the composition of the microbiota, its biophysical localization within the intestinal tract and its metabolic outputs. The gut microbiome and its key metabolic outputs, such as short chain fatty acids and tryptophan metabolites contribute to maintenance of intestinal immunity by promoting barrier function, regulating the host mucosal immune system and maintaining the function of gut-associated immune cell populations. Loss of rhythmic host-microbiome interactions disrupts host immunity and increases risk of inflammation and metabolic complications. Here we review factors that drive circadian variation in the microbiome, including meal timing, dietary composition and host circadian clocks. We also consider how host-microbiome interactions impact the core molecular clock and its rhythmic outputs in addition to the potential impact of this relationship on circadian control of immunity.
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Mathematical modeling of the circadian rhythm of key neuroendocrine-immune system players in rheumatoid arthritis: a systems biology approach.
Meyer-Hermann, M, Figge, MT, Straub, RH
Arthritis and rheumatism. 2009;(9):2585-94
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Abstract
OBJECTIVE Healthy subjects and patients with rheumatoid arthritis (RA) exhibit circadian rhythms of the neuroendocrine-immune system. Understanding circadian dynamics is complex due to the nonlinear behavior of the neuroendocrine-immune network. This study was undertaken to seek and test a mathematical model for studying this network. METHODS We established a quantitative computational model to simulate nonlinear interactions between key factors in the neuroendocrine-immune system, such as plasma tumor necrosis factor (TNF), plasma cortisol (and adrenal cholesterol store), and plasma noradrenaline (NA) (and presynaptic NA store). RESULTS The model was nicely fitted with measured reference data on healthy subjects and RA patients. Although the individual circadian pacemakers of cortisol, NA, and TNF were installed without a phase shift, the relative phase shift between these factors evolved as a consequence of the modeled network interactions. Combined long-term and short-term TNF increase (the "RA model") increased cortisol plasma levels for only a few days, and cholesterol stores started to become markedly depleted. This nicely demonstrated the phenomenon of inadequate cortisol secretion relative to plasma TNF levels, as a consequence of adrenal deficiency. Using the RA model, treatment with glucocorticoids between midnight and 2:00 AM was found to have the strongest inhibitory effect on TNF secretion, which supports recent studies on RA therapy. Long-term reduction of TNF levels by simulation of anti-TNF therapy normalized cholesterol stores under "RA" conditions. CONCLUSION These first in silico studies of the neuroendocrine-immune system in rheumatology demonstrate that computational biology in medicine, making use of large collections of experimental data, supports understanding of the pathophysiology of complex nonlinear systems.
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[To test the impact of hypnotherapy upon immunity and circadian rhythms among palliative cancer patients: a promising goal?].
Kwiatkowski, F, Bignon, YJ
Pathologie-biologie. 2007;(3-4):186-93
Abstract
Epidemiological and clinical researches in the borderline domain between psychology and cancer have produced consequent results, despite the large variety of employed approaches and aimed goals: these results permit to define domains where new investigations still appear promising. If randomized prospective controlled trials that test the impact of psychosocial interventions, constitute to our mind a strategy that must not be bypassed, a special attention should be focussed on the following topics: 1) it seems necessary to add to standard goals (survival and quality of life) the evaluation of the impact on immunity and main biological rhythms (circadian and ultradian). Specific questionnaires should be included (pain, sleep, mood, self-esteem, life events...) and others may need to be developed or adapted (sexuality, spirituality, coping with death); 2) among types of psychosocial management, hypnosis and/or learning of self-hypnosis appears to be a modality of choice since some results have already been obtained on immune pathologies and also on cancer. Mixed to an approach of clinical psychology, such a management could arouse behavior changes toward pathology but also promote an improvement of biological rhythms (action on sleep...) and perhaps, by the way, an immune rebound; 3) on a methodological point of view, trials cannot be double-blind. The effort must then concern sample sizes, that were often insufficient in many trials, but also targeted populations: palliative cancer patients with a good performance status seem more relevant for this type of investigation, since psychosocial interventions usually improve quality of life.