Archive | January 2016

Attempting Transdisciplinary Research

Over recent years, the field of “systems biology” has been emerging.  It is throwing light on areas that have long been a mystery.  But how should systems biology develop into a mature discipline? Read More…

How Microbes Influence Evolution

Associations between microbes and health have been made by researchers for a number of decades, but the question has remained by what mechanism are microbes influencing human health?

A new field of chronobiomics is emerging that may provide an answer this question through researching the associations between microbes and biorhythms. The extent to which large microbial populations, are affected by and/or entrain biorhythms is still being explored, but evidence suggests strong links.

This could also have implication for those who are interested in the concept of the holobiont – which suggests that microbes could have a key role to play in evolution.

Microbes Can Influence Host Gene Expression. 

Recent research suggests that microbe have some influence on the circadian rhythms of their hosts.

The bacterial bioluminescence (from the bacteria ‘Vibrio fischeri’) regulates expression of a host cryptochrome gene in the squid-vibrio symbiosis. This finding that bacteria can directly influence the transcription of a gene encoding a protein implicated in the entrainment of circadian rhythms provided the first evidence for the role of bacterial symbionts in influencing, and perhaps driving, peripheral circadian rhythms in the host. In mammals, biological rhythms of the intestinal epithelium and the associated mucosal immune system regulate such diverse processes as lipid trafficking and the immune response to pathogens. EAC Heath-Heckman 2013.

C A Thaiss et al 2016 found that the intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis. And that the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.

Microbes can partially disable Hnf4a in mice and zebrafish and perhaps obstruct its protective role (throughout evolution, Hnf4a appears to protect against microbial contributions to inflammatory bowel diseases). When Hnf4a is fully disabled, microbes stimulate patterns of gene expression in animals that are associated with inflammatory bowel diseases. Similar effects in zebrafish and mice suggests that this is a common feature of host-microbe interactions that might have existed in our common (vertebrate) ancestors. J M Davidson et al 2017 

The integral liver transcription factor, hepatocyte nuclear factor 4 alpha (HNF4a) is a key target for circadian and glucocorticoid-mediated orchestration of liver gene expression. Thus, glucocorticoids, as well as body temperature, are likely to be key synchronizers of the liver clock, acting through transcriptional cascades involving mPer2 and other regulators. Key liver-specific proteins, such as the glucocorticoid-responsive HNF4a, likely play roles in local synchronization and circadian transcriptional programming. A B Reddy 2007.

In mice gut microbial colonization influences rhythmic signalling events in the ileal epithelium downstream of toll-like receptors (TLRs). This, in turn, regulates the organization of molecular clock activity and glucocorticoid production in the intestine.. A Mukherji 2013. Glucocorticoids in turn play a key role in circadian cell cycle rhythms. T Dickmeis 2007.

Nearly all aspects of digestion and detoxication – from gastric emptying time to fat processing and xenobiotic degradation by the liver – are under circadian control (Dallmann et al., 2014). Read More…