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Intermittent Fasting and Calorie Restriction Positively Impact Gut Microbiome

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Diet and changes and the microbiome

The gut microbiome – the diverse and complex population of microorganisms that inhabit the gastrointestinal tract – has been linked to diet and obesity. To date, however, these factors have not been studied together in the context of obesity treatment.

Dr. Maggie Stanislawski, assistant professor in the department of biomedical informatics, explores the role of the gut microbiome in obesity and cardiometabolic disease at the University of Colorado (CU). Over in the UC Department of Medicine, a team of researchers led by Dr. Vicki Catenacci, associate professor, planned a clinical trial comparing the effects of intermittent fasting (IF) and daily caloric restriction on weight loss over a one-year period. IF, where food intake is restricted to a certain window of time, has become increasingly popular as a diet practice over recent years and is hailed by many celebrities as their “go-to” approach to keeping trim. Catenacci and colleagues’ study focused on whether IF could be an effective dietary strategy for treating obesity, specifically.

Stanislawski saw an opportunity to add extra layers to the study by examining the effects of the dietary interventions on gut microbiome and DNA methylation profiles. Alongside several other researchers across the UC Anschutz Medical Campus, she conducted a three-month pilot study on two out of five cohorts recruited for the trial. Data was gathered from 47 adults – 77% of which were female – that were classified as overweight or obese based on their BMI scores. 

In the IF group, participants were required to fast over three non-consecutive days each week, limiting their food intake to ~25% of their usual consumption. On non-fast days, they were permitted to eat whatever they wanted. In the caloric restriction group, the participants reduced their calories by the same amount each day – approximately 30% of their maintenance calories. All participants submitted blood and fecal samples at baseline and three months after the study commenced.

Weight loss strategies shift microbiome diversity

Stanislawski and colleagues analyzed the fecal samples using 16s RNA sequencing, discovering that both interventions positively impacted the diversity of the microbiome after three months. “There are various measures of the microbiome that we tend to think about,” Stanislawski explains. “One of them is called alpha diversity, and these measures represent the diversity of the different types of microbes in an environment. While not always true, a more diverse and robust microbiome is often associated with better health and leanness.” She adds that the more microbes you have in your gut, the more chance you have that these microbes can respond to diverse health impacts.

"We looked at different measures of alpha diversity that take into account various features of diversity," Stanislawski says. "They all increased in the first three months of this intervention, which is great. When we looked at differences between the two intervention groups, there weren't really any differences in terms of alpha diversity. This means that you can choose a dietary weight loss strategy that works for you, and either way your microbiome will likely shift and increase diversity.”

The researchers also identified associations between the gut microbiome composition and methylation levels of genes involved in key physiological processes.

What is DNA methylation?

An epigenetic modification whereby a methyl group (CH3) is added to or removed from specific sites on the DNA strand. DNA methylation can influence gene activity and expression.

“Our results reinforce this idea that we may see a lot of changes in microbes that are associated with diet and obesity during weight loss,” Dr. Iain Konigsberg, research instructor in biomedical informatics co-author of the study, says. “We also see abundance of microbes associated with DNA methylation levels in genes that we know are involved in relevant processes in the body, such as metabolism.”

The researchers emphasize that data was only collected from two out of five recruitment cohorts from the parent trial. “Thus, the sample size is relatively small and not representative of the general population of those with overweight and obesity in terms of race, ethnicity, socioeconomics and other factors,” they write in the paper.

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Stanislawski and colleagues add that their use of short-read 16S rRNA sequencing limited the ability to evaluate the functional capacity of the microbes present in the gut. They believe their pilot work creates a platform for future studies that may adopt a multi-omics approach for assessing the biological impact of lifestyle interventions such as dietary practices.

Reference: Hill EB, Konigsberg IR, Ir D, et al. The microbiome, epigenome, and diet in adults with obesity during behavioral weight loss. Nutrients. 2023;15(16). doi: 10.3390/nu15163588

This article is a rework of a press release issued by the University of Colorado. Material has been edited for length and content.