Su J, Wang Y, Zhang X, et al. Remodeling of the gut microbiome during Ramadan-associated intermittent fasting. Am J Clin Nutr. 2021;113:1332-1342.
To analyze the biological effects of a one-month Ramadan-associated intermittent fast on the gut microbiome
Prospective trial of 2 separate cohorts during Ramadan fasting
There were 2 cohorts: a young adult cohort and a middle-aged cohort. The middle-aged cohort had 10 nonfasting participants who served as the control; there was no control group within the young adult cohort:
- Cohort 1 (young, healthy) 2016 Ramadan: age 18.63±1.75; n=30 fasting
- Cohort 2 (middle-aged, healthy) 2018 Ramadan: age 39.9±6.4; n=27 fasting, n=10 non-fasting
All volunteers observed an overnight fast that lasted approximately 16 hours in observance of Ramadan, the 9th month of the Muslim year when those practicing the Islamic faith fast from dawn to sunset for 30 days. All of the participants in the young cohort were male, and 70% of the participants in the middle-aged cohort were male. Due to regional variations in the diets of the 2 cohorts, the young cohort was reported as having rice as a staple food in their diet, while the dietary staple for the middle-aged cohort was wheat.
Exclusion criteria included obesity, diabetes, hypertension, arthritis, chronic respiratory disorders, and gastrointestinal disorders. The use of prescription antibiotics in the month before the fasting period was also exclusionary.
The primary outcome was the analysis of the gut microbiome composition pre- and post-Ramadan. Gut microbiota was analyzed for composition, diversity, and taxonomic abundance using next-generation sequencing and 16s ribosomal RNA gene sequencing, along with data processing techniques in both cohorts.
Healthy, young cohort: Only fecal samples were used for comparison. There were 3 time points: day one of Ramadan (T1), day 15 (T2), and day 30 (T3).
Given these far-reaching effects, it makes sense that changes to microbial composition could be a key factor in the diverse health benefits of intermittent fasting.
Healthy, middle-aged cohort: Fecal samples were analyzed the same way as they were in the young cohort. The time points for the middle-aged cohort were the start of Ramadan (T1), the end of Ramadan (T2), and 1 month after the end of Ramadan (T3). In addition to fecal samples, the researchers assessed body composition, as well as several blood parameters (comprehensive metabolic profile, hemoglobin A1c, lipid panel, and uric acid). This cohort also filled out a food frequency questionnaire (FFQ).
Secondary outcomes included blood parameters, body composition, and food intake.
Both cohorts experienced major shifts in microbiome composition that were similar to each other during the fasting period, while the nonfasting control in the middle-aged group experienced no significant composition changes in the microbiome. In particular, both cohorts displayed an enrichment of butyric acid-producing Lachnospiraceae. The authors point out that high concentrations of Lachnospiraceae are associated with a reduced risk of cancer, improved inflammatory bowel disease, better mental health, reduced allergies, and improved cardiorespiratory health.
The young cohort had an increase in the overall diversity of the gut microbiota (Shannon-Weaver index) while the middle-aged cohort did not. In the middle-aged cohort, microbial composition largely returned to baseline for most taxa 1-month post-fasting, while shifts in some remained.
The fasting groups also experienced weight loss and had improved liver enzyme activity.
More than 24% of the world’s population is Muslim.1 Ramadan offers a convenient way to assess the physiological changes of a 16-hour fast on large populations. It is expected that fasting during Ramadan, like fasting in general, should confer health benefits, and so far, this seems to be the case. According to a 2014 analysis of 21 different studies, Ramadan fasting led to positive metabolic effects and weight loss.2 That analysis, as well as a 2021 study, indicated that Ramadan fasting can reduce inflammation and enhance immunity.3
In 2020, Natural Medicine Journal published a peer-reviewed paper on the subject that discussed mechanisms of action and clinical applications of intermittent fasting.4 A 2019 review of 12 different studies found that intermittent fasting reduced BMI and improved glycemic control, insulin resistance, and adipokine concentrations compared to adults not doing intermittent fasting.5 A 2020 review found that intermittent fasting not only reduced the risk of cardiovascular disease, but also improved cognition in both obese and nonobese individuals.6
Shortly after the study under review here was published, another small pilot study showed that fasting during Ramadan led to significant changes in the gut microbiome.7 General fasting, which is done by eating a very early dinner and/or a late breakfast has already been established as a means of shifting the gut microbiota.8 These studies on Ramadan fasting imply that the time of day that the fasting takes place (daytime vs nighttime) does not change the overall effect of increasing diversity and shifting the composition of the microbiota. The ability to shift the microbiota composition has broad clinical significance since everything from depression to diabetes, cardiovascular disease to cancer, and more can be traced back, at least in part, to the gut microbiome.9 Given these far-reaching effects, it makes sense that changes to microbial composition could be a key factor in the diverse health benefits of intermittent fasting.
Intermittent fasting is not appropriate for all patients because it is a stress on the body. Within religious observations such as Ramadan, many subsets of the population are encouraged to avoid fasting. This includes prepubescent children, the elderly, the frail, and pregnant women, to name a few.10
Fasting as a means to improve health may be one of the simplest and most economical tools we have in integrative medicine. That said, as with any therapy, caution should be used in those who are frail, those with acute conditions, and those in whom skipping meals is considered contraindicated.
One study limitation was the fact that there was no control group in the young male cohort, which detracts from the young male cohort group results. That said, the control group in the middle-aged cohort validated that without fasting there is little change at all in the microbial composition of the gut.