Microbiome dynamics in obesity.
Science. Nov 2018. doi: 10.1126/science.aav6870
COMMENT: An interesting article about temporal and spatial dynamics of the intestinal microbiome in obesity and about how it influences central features of metabolic disease. The authors highligh 3 main points that could explain this impact of the microbiome in obesity.
Point 1- Gut microbiome influences the circadian biology of the host:
In our initial experiments, we discovered that the gut microbiome in both mice and humans undergoes oscillations in a 24-hour rhythm (6). These diurnal fluctuations encompass multiple characteristics of the microbiota, such as taxonomic composition, metagenomic function, metabolite secretion, and biogeographical localization within the intestine We then showed that daily oscillations in the intestinal microbial community influence the circadian biology of the host, by determining the oscillatory pattern of serum polyamines. These, in turn, orchestrate the circadian transcriptional program in metabolic tissues. The host-microbiome interface can thus be viewed as a dynamic interplay that undergoes hour-scale fluctuations over the course of a day. Aberrations in this coordinated daily interplay may contribute to the development of obesity and its complications.
Point 2 - Gut microbiome from obese individuals increases the degradation of dietary flavonoids, which diminishes energy expenditure due to the reduction of metabolic activity in adipose tissue:
We found, in mice, that a period of obesity induced long-lasting alterations in the composition of the microbiome that persisted even after the host organism returned to normal weight. This “memory-like” behavior of the microbiome mediated the susceptibility of the formerly obese host to accelerated weight regain. The weight-modulating effect of the microbiome was achieved by the degradation of dietary flavonoids, which resulted in reduced metabolic activity of adipose tissue and diminished energy expenditure. When we restored flavonoid levels, energy expenditure was normalized, and weight regain was ameliorated.
Point 3 - Gut microbiome from obese and diabetic individuals increses the susceptibility to enteric infection and systemic inflammation by increasing bacterial translocation trough intestinal epithelial barrier:
Intestinal epithelial cells normally provide a tight barrier that separates intestinal bacteria from the systemic circulation. In analyses of obese and diabetic mice, we found that chronic hyperglycemia led to a breakdown of the epithelial barrier and facilitated translocation of intestinal bacterial components into the bloodstream, where they promoted systemic inflammation
The authors propose a new microbiome-based intervention for obesity treatment oriented to the modulation of intestinal metabolites with new drugs or methods that they call “postbiotics” (analogously to the termed prebiotics and probiotics).
In summary, this could be 3 metabolites susceptible to be manipulated by "postbiotics" for obesity treatment:
- Polyamines: Gut microbiome from obese individuals alterates the oscillatory pattern of serum polyamines involved in circadian rhythms
- Flavonoids: Gut microbiome from obese individuals increases the degradation of dietary flavonoids, which diminishes energy expenditure due to the reduction of metabolic activity in adipose tissue
- Glucose: Gut microbiome from obese and diabetic individuals increses bacterial translocation trough intestinal epithelial barrier augmentating the susceptibility to enteric infection and systemic inflammation
As such, this work provides evidence for a powerful new therapeutic concept, which—rather than interfering with the intestinal microbial community itself (via prebiotics and probiotics)— may be based on the modulation of intestinal metabolites with a direct effect on host metabolism (analogously termed “postbiotics”)