Intermittent fasting shows potential benefits for obesity treatment and brain-gut-microbiome health

By Dr. Priyom Bose, Ph.D.Reviewed by Danielle Ellis, B.Sc.Mar 26 2023

A recent Nutrients journal study by researchers at the David Geffen School of Medicine at the University of California, Los Angeles, has discussed the effects of time-restricted eating on BGM and reviewed its promising effects in obesity treatment.

Study: Brain–Gut–Microbiome Interactions and Intermittent Fasting in Obesity. Image Credit: Kreminska / Shutterstock

Introduction

A major global public health problem is the obesity epidemic and its metabolic consequences. A body mass index (BMI) greater than 30 kg/m² is defined as obesity, and an individual is said to be extremely obese when the BMI exceeds 40 kg/m².

There are several underlying causes of obesity, of which dysregulations within the brain–gut–microbiome (BGM) are crucial.

The Effect of Altered BGM Interactions on Obesity

Significant levels of research have indicated the changes in bidirectional signaling within the BGM system in obese individuals. These changes are mediated by endocrine, metabolic, neural, and immune system-mediated mechanisms. This observation has been verified on specialized cells (e.g., enteroendocrine and enterochromaffin cells) present in the gut, which are sensitive to many gut microbial metabolites, such as short-chain fatty acids (SCFA).

Following ingestion of dietary fiber, i.e., Microbiota Accessible Carbohydrates (MACs), the gut microbe produces SCFA. Subsequently, it sends signals to the brain via the bloodstream or vagal afferent pathways.

The BGM system is key in regulating ingestive behaviors, which aids in keeping the body weight stable. Despite its complex nature, strategies to treat dysregulated ingestive behavior and obesity continue to be at the forefront of obesity research.

The temporal dimension of food intake has only recently received widespread scientific attention. This food intake regulates the gut microbiome and aids in the bidirectional interaction between the brain and the gut.

Environmental factors affecting BGM interactions in obese individuals

Cheap and highly processed foods are widely available in the developed world. Research has shown that stress can lead to increased consumption of such foods and weight gain.

Additionally, increased consumption of highly palatable foods gradually reduces the reward thresholds of such foods, reflecting a reduction in dopamine levels in the brain. The adult microbiome is resistant to short-term dietary changes, but longer-term consumption of such foods could change the gut microbial diversity.

The marketing strategies of the US food industry have played a key role in creating and sustaining the unhealthy eating habits of the majority of the American population. Additionally, research has shown that portion sizes are directly related to food addiction and obesity. 

Clinical implications and treatment of obesity

Several strategies have been formulated with short-term effectiveness in weight reduction and metabolic health improvements. Some of these strategies involve special diet regimes and redistribution of macronutrients (e.g., carbohydrates, fats, and proteins).

However, the impacts of these strategies on the gut microbiome and the role of gut microbial dysbiosis on weight loss are not clear. Also, the aforementioned diet regimes have shown significant short-term improvements, but the long-term effects are still inconclusive. 

Several obesity treatments, including different types of bariatric surgery, focus on altering how the upper gastrointestinal (GI) tract assimilates and processes food. Bariatric surgery is the only intervention that achieves robust long-term weight reduction, but it is invasive, costly, and has side effects.

Research among patients undergoing bariatric surgery has shown that the alterations in microbial metabolism of aromatic amino acids and glutamate and the gut microbiome composition are linked to reduced food addiction, appetite, and change in food preferences.

Anti-obesity medications aimed at suppressing appetite constitute another weight loss strategy. Some common drugs that target the hypothalamus are naltrexone, phentermine, bupropion, and lorcaserin. Unfortunately, these drugs have demonstrated limited effectiveness, making them unreliable for weight loss. Further, their effects on the gut microbiota are still unknown.

Time-restricted Eating (TRE) and Obesity

TRE has gained significant recent attention, which combines 6-8 hours of mainly plant-based food intake daily and 16-18 hours of a ketogenic phase. As opposed to intermittent fasting, TRE does not require a reduction in caloric intake. The ketogenic phase allows the body to burn fat instead of drawing from a continuous glucose supply.

During this phase, the liver produces ketones by metabolizing body fat. The cellular responses switched on during the ketogenic phase are hypothesized to remain active even when eating resumes. Most of the research in this area has been on rodents, and despite the impressive findings, clinical trial results to establish the efficacy of TRE are limited and inconsistent.

Conclusions

Complex bidirectional interactions within the BGM system regulate ingestive behavior. Many environmental and dietary factors have been detected that alter the regulated communication within the BGM system, leading to hedonic food intake.

The temporal pattern of food intake has been seen to play a key role in obesity and associated metabolic consequences. Based on the results obtained from mice models, TRE, combined with a plant-based diet, appeared to offer the highest long-term benefits.

However, more human studies are needed to establish the beneficial effects of TRE to cement this form of intervention as a cost-effective obesity therapy.