MicrobiotaMi Comment 02_21 by  Giulia Colombo

Related Journal Article: When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis. Cell Metab. 2020 Mar 3;31(3):448-471. doi: 10.1016/j.cmet.2020.02.008

The circadian rhythm and the microbiota-gut-brain axis: a recurrent appointment with the neighbours

Teichman et al.’s recent review deals with the interactions between the microbiota-gut-brain axis and circadian rhythmicity, a topic that reminds us how reductive it is to think about ourselves as lonely bodies: we are more similar to small-scale ecosystems, instead, for our microbiota partners.

Around 5%–10% of the genes in the body are regulated by circadian oscillations, so the operation of cells, tissues and organs in processes such as immune function, body temperature, blood pressure, energy allocation, metabolism, absorption of nutrients, insulin levels, and hormone secretion are all synchronized by one dominant oscillator, which, in mammals, is in the suprachiasmatic nucleus of the hypothalamus. The circadian rhythm can be disrupted by environmental insults, gene polymorphisms or behavior. Social expectations often impose negative environmental factors on circadian rhythm such as jet lag, shift work, social jet lag, inconsistent eating times and high-fat diet. And the microbiota is both modulated by, and a modulator of, the central and peripheral clocks.

What happens in turn to the microbiota during the 24 hours? About 35% of the measured bacterial operational taxonomic units (OTUs) in humans undergo temporal behavioral rhythmicity, and microbial community composition and abundance also fluctuate as a function of time. Host circadian rhythms influence the microbiota in many ways: deficiencies in clock genes cause perturbations of the gut microbiota, that can be rescued by food restriction or timing; both timed and restricted feeding can induce changes to the rhythmicity of the gut microbiota; under 24 h dark or light conditions, mice lose all gut microbial diurnal rhythmicity and this is worsened by high-fat diet. The other way round, germ-free and antibiotic-treated mice experience an alteration of their peripheral and gut clocks; microbiota-derived metabolites including short-chain fatty acids (SCFAs) and bile acids alter circadian rhythms, and dietary polyamines are needed for a healthy microbiota and a normal circadian gene expression in the gut. SCFAs are introduced through a fiber-rich diet, as well, and they help the microbiota-to-clock entrainment.

But which are, mechanistically, the links between the circadian rhythm and the microbiota? One is metabolism: the gut microbiota diversity increases with feeding and clock genes are related to systemic regulation of food intake; the second is hormones, as their oscillatory pattern of secretion is altered in germ-free animal models; and the immune system, as the formation of a well-functioning mucosal immune system depends on a healthy commensal bacterial population in the host’s gut at birth and TLRs are key converters of bacterial signals into rhythmic gene expression.

Since there is a strong overlap of diseases related to the gut microbiota and physiological circadian cycles, such as psychiatric and metabolic disorders, further studies are needed to elucidate how modulating the microbiota could be helpful to patients.

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