Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue

Abstract

Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

“…; Pluznick, ; Tahara et al . ). Gut microbial‐derived SCFAs are also increasingly implicated in emotional processing and behaviour, as butyrate has been shown to ameliorate cognitive impairments in a model of vascular dementia and in mid‐adult high‐fat‐diet‐induced obese mice (Liu et al .…”

“…It is therefore essential to emphasise that physiologically relevant levels of acetate and propionate have been reported to directly influence the brain (Perry et al 2016;Hoyles et al 2018). Considering the plethora of ways in which they can affect the host, it's not surprising that SCFAs have been implicated in numerous physiological functions such as gastrointestinal functionality, host metabolism, blood-pressure regulation, circadian rhythm and (neuro)immune function (Koh et al 2016;Erny et al 2017;Pluznick, 2017;Tahara et al 2018). Gut microbial-derived SCFAs are also increasingly implicated in emotional processing and behaviour, as butyrate has been shown to ameliorate cognitive impairments in a model of vascular dementia and in mid-adult high-fat-diet-induced obese mice Arnoldussen et al 2017), and propionate is able to reduce anticipatory reward responses to high-energy foods in the human striatum (Byrne et al 2016).…”

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

“…An interesting model using the cyclical parthenogenetic insect Daphnia pulex showed that temperature altered energy allocation, as expected, but did not systematically match with the consequences of calorie restriction in terms of longevity (Schwartz et al ., ). Factors such as the circadian rhythm and quality of light are seldom taken into account, despite the fact that they have a considerable impact on the host (Cribbet et al ., ) as well as on microbial life cycles (Borriss et al ., ; Tahara et al ., ). The consequence is that the food intake time points have substantial consequences that are rarely considered seriously (Hutchison et al ., ).…”

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

“…The precise mechanisms of how microbiota can exert this role need further investigation. Microbiota‐derived metabolites such as short‐chain fatty acid, bile acids, lipopolysaccharides, and B vitamins have been implicated in mediating the information from the gut microbiota to the host . Most of these studies focused on the influence of microbiota on the host's circadian clock machinery.…”