As these GEITP pages continue to emphasize, multifactorial traits (phenotypes) reflect the contributions of [a] genetics, [b] epigenetic factors, [c] environmental effects, [d] endogenous influences, and [e] each person’s microbiome. The topic of this email [see attached article and editorial] is the gut microbiota. Authors propose that — in today’s Western society — the large increase (epidemic?) in certain complex diseases (e.g. obesity, type-2 diabetes, autism spectrum disorder) might be caused by disruptions in several key aspects of our lifestyles. Modern humans are more likely to live in urban areas, be more sedentary, experience artificial lighting (and flickering TV and video games), and eat a typical “Western” diet (high in calories and fat, low in fiber). Epidemiological studies suggest that these factors might be at least partially responsible for the rise of metabolic and inflammatory disorders — although precisely how lifestyle promotes such conditions is not understood.
Authors [see attached article and editorial] identified one possible mechanism: disrupted cross-talk between the body clock in the gut and the bacterial communities living there (the microbiota). The circadian clock, an evolutionally conserved body clock system, mediates the interplay between environment and host. In a regular light-dark cycle, circadian rhythms facilitate anticipated responses to an expected (repetitive) environmental signal (such as fasting during normal sleep.). However, it is not just light that has the power to train the body’s circadian rhythms; food intake can also influence daily cyclical changes in the intestine and liver. In this way, shifts in waking or eating times relative to light-dark cycles (e.g. as occurs in night-shift workers or in people experiencing jet lag, which are forms of circadian misalignment) can disrupt circadian systems and effectively disconnect some biological responses, including metabolic functions.
Authors [see attached article] show that the intestinal microbiome — programs day-night metabolic rhythms in the mouse small intestine through histone deacetylase-3 (HDAC3). The microbiota induce expression of intestinal epithelial HDAC3, which is recruited rhythmically to chromatin [the material (protein, RNA, and DNA) of which chromosomes of organisms (other than bacteria) are made of], and produces synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned independently to co-activate estrogen-related receptor-a (ESRRA) — inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36, and enhancing lipid absorption and diet-induced obesity. These results reveal that HDAC3 integrates microbial and circadian cues for regulation of diurnal metabolic rhythms and pinpoint a key mechanism by which the microbiome controls host metabolism…!! 😊
· Science Sept 2019; 365: 1428-1434 & editorial pp 1379-80