Researchers here show that intermittent fasting alters the gut microbiome in ways that likely increase the production of butyrate. This metabolite is known to produce beneficial downstream effects, such as upregulation of BDNF and neurogenesis. As research into the gut microbiome in health and aging continues, an increased knowledge of the mechanisms by which fasting and calorie restriction act to improve health will be one of the outcomes.
Experiments in experimental rodents and observations in human volunteers or patients suggest that the beneficial effects of intermittent fasting can only partly be explained by reduced calorie intake. A plethora of alternative mechanisms mediating the effects of intermittent fasting have been brought forward and can roughly be grouped in three categories involving mechanisms involving circadian biology, altered lifestyle, and remodeling of the gut microbiome.
The notion that the latter is especially instrumental for mediating the beneficial effects of intermittent fasting is supported by many observations in experimental animals, including that white adipose tissue browning provoked by intermittent fasting requires an intestinal flora, or that restructuring of the gut microbiome by intermittent fasting counteracts retinopathy in diabetic mice. The effects of intermittent fasting on the human microbiome remain, however, largely uncharacterized, and in view of the problems associated with extrapolating data in experimental rodents to humans, it would be important to establish the effects of intermittent fasting in our species as well.
Prompted by the above mentioned considerations, we decided to characterize the effects of a monthly episode of intermittent fasting on the human gut microbiome and to contrast the results with nonfasting controls and with the effects of cessation of intermittent fasting following the intervention.
We observed in two independent cohorts, sampled in two different years, that Ramadan-associated intermittent fasting induces substantial remodeling of the gut microbiome. Importantly, we established that intermittent fasting in humans is especially associated with an upregulation of butyric acid-producing Lachnospiraceae in a manner that correlates to improvement in human physiologic surrogate markers such as blood glucose and BMI. Intermitting fasting-provoked upregulation of Lachnospiraceae thus may provide a rational explanation for at least some of the beneficial effects reported for intermittent fasting in humans.