Intermittent fasting changes the composition of the gut microbiome, according to new research . An increase in the abundance of a group of bacteria known as Lachnospiraceae may explain some of the health benefits linked with dietary restriction.
A natural experiment
Intermittent fasting—the repeated, severe restriction of food intake—is an extremely reliable method of extending lifespan in a wide range of species. Though its efficacy has not been demonstrated in humans, many people find the idea attractive. However, voluntarily refraining from eating can be challenging, especially in the long term. Uncovering the mechanistic basis for the effects of intermittent fasting could help us find alternative approaches to gain the same benefits.
To investigate this in humans rather than lab animals, researchers in China and the Netherlands took advantage of the fact that many Muslims voluntarily refrain from eating between sunrise and sunset during the Islamic lunar month of Ramadan. This provided a ready-made cohort to measure the changes caused by intermittent fasting. Because studies in lab animals have suggested that alterations to the gut microbiome provide some of the benefits of intermittent fasting, the team decided to focus on the composition of the gut microbiome and whether it correlated with physiological metrics.
An important change
The researchers measured changes in the gut microbiome and physiological metrics in two age cohorts of men who were fasting during Ramadan. Unfortunately, only one of the cohorts had matched non-fasting controls, making the data from the other cohort less valuable. Samples from both cohorts were collected at the start of Ramadan (when intermittent fasting began) and at the end of the month. The team also collected samples from one of the cohorts (the one with a control group) one month after the end of Ramadan, enabling them to check whether the changes persisted.
The researchers reported a “substantial remodeling of the gut microbiome” in both cohorts. They note as especially important an increase in Lachnospiraceae as a result of fasting, and this increase correlated with improvements in physiological markers such as blood glucose and BMI. The increase in Lachnospiraceae and the improvement in physiological markers both disappeared after fasting stopped, meaning the effects were reversible rather than long-term.
Lachnospiraceae produce butyric acid, a bioactive substance that is known to provide metabolic benefits by affecting the brain-gut neural circuit and that has been linked with reduced cancer incidence, improvement of inflammatory bowel disease, and other health benefits. The researchers therefore speculate that the increase in Lachnospiraceae may be an important factor in the health benefits of intermittent fasting.
Background: Intermittent fasting is a popular dietary intervention with perceived relatively easy compliance and is linked to various health benefits, including weight loss and improvement in blood glucose concentrations. The mechanistic explanations underlying the beneficial effects of intermittent fasting remain largely obscure but may involve alterations in the gut microbiota. Objectives: We sought to establish the effects of 1 mo of intermittent fasting on the gut microbiome. Methods: We took advantage of intermittent fasting being voluntarily observed during the Islamic faith-associated Ramadan and sampled feces and blood, as well as collected longitudinal physiologic data in 2 cohorts, sampled in 2 different years. The fecal microbiome was determined by 16S sequencing. Results were contrasted to age- and body weight–matched controls and correlated to physiologic parameters (e.g., body mass and calorie intake). Results: We observed that Ramadan-associated intermittent fasting increased microbiome diversity and was specifically associated with upregulation of the Clostridiales order–derived Lachnospiraceae [no fasting 24.6 ± 13.67 compared with fasting 39.7 ± 15.9 in relative abundance (%); linear discriminant analysis = 4.9, P < 0.001 by linear discriminant analysis coupled with effect size measurements] and Ruminococcaceae [no fasting 13.4 ± 6.9 compared with fasting 23.2 ± 12.9 in relative abundance (%); linear discriminant analysis = 4.7, P < 0.001 by linear discriminant analysis coupled with effect size measurements] bacterial families. Microbiome composition returned to baseline upon cessation of intermittent feeding. Furthermore, changes in Lachnospiraceae concentrations mirrored intermittent fasting–provoked changes in physiologic parameters. Conclusions: Intermittent fasting provokes substantial remodeling of the gut microbiome. The intermittent fasting–provoked upregulation of butyric acid–producing Lachnospiraceae provides an obvious possible mechanistic explanation for health effects associated with intermittent fasting.
Teasing apart the effects of intermittent fasting is important not only because it might offer a path to an alternative approach but also because it could enable us to separate potentially beneficial and harmful effects. It’s also interesting to note that while the diversity of the gut microbiome increased in both age cohorts, the change was only significant in the younger cohort, “probably because of age-related factors such as immunosenescence and differences in nutrient absorption.” Further research into the interplay between age, health, diet, and the gut microbiome could help us learn how to manipulate these dynamics to our advantage.
 Su, J, Wang, Y, Zhang, X, Ma, M, Xie, Z, et al. Remodeling of the gut microbiome during Ramadan-associated intermittent fasting. The American Journal of Clinical Nutrition (2021) doi: 10.1093/ajcn/nqaa388