In a recent review published in the journal Cell, researchers discussed recent advances in molecular nutrition. They focused on pharmaceutical and dietary interventions to manage energy balance and their interactions with the gut microbiome in humans. Further, they explored emerging dietary patterns and the implications of microbiome research on nutrition.
Review: Digesting the complex metabolic effects of diet on the host and microbiome. Image Credit: FOTOGRIN / Shutterstock
Background
Over the past 50 years, molecular nutrition has evolved from focusing on micronutrients to studying macronutrients and dietary patterns, especially due to the rise in obesity. A growing body of evidence emphasizes the role of the gut microbiome in regulating energy metabolism and dietary responses. This has led to the concept of precision nutrition, which customizes dietary recommendations based on an individual's genetic and microbiome profiles. Large-scale studies such as the Personalized Responses to Dietary Composition Trial (PREDICT) have shown the potential of incorporating microbiome data to enhance metabolic health outcomes. However, further research is needed to validate precision nutrition and integrate it into clinical practice.
The present review focuses on recent advancements in diets, energy balance, and the gut microbiome, excluding discussions on dietary sugars, plant-based diets, genetically modified organisms (GMOs), and undernutrition. The authors aim to illustrate rapid progress and general concepts applicable to other areas of nutrition research.
Emerging dietary interventions
Recent developments in human nutrition challenge the traditional fat restriction guidelines, embracing diets with moderate to high fat intake. The Mediterranean diet (MD), rich in whole grains, legumes, fruits, vegetables, nuts, seeds, and olive oil, has shown benefits in reducing body weight, body mass index, blood pressure, low-density lipoprotein, triglycerides, insulin resistance, and inflammation, lowering mortality and risks of type 2 diabetes (T2D) and cancers. Its mechanisms include lipid-lowering, oxidative stress protection, and nutrient-sensing pathway inhibition. MD positively affects the gut microbiome, increasing fiber-degrading taxa and beneficial metabolic phenotypes. The ketogenic diet (KD), very low in carbohydrates and high in fat, offers slight weight loss and improved glycemic control but has potential downsides like cardiovascular risks, nutrient deficiencies, and harmful gut-bacterial metabolites. KD uniquely alters the gut microbiota and protects against seizures and autoimmune diseases in a microbiota-dependent manner. Calorie restriction (CR), reducing dietary intake while maintaining nutrition extends lifespan, improves healthspan, reduces fat, and enhances insulin sensitivity, with gut microbiota changes mediating these benefits in mice, though human causal links remain unconfirmed. Intermittent fasting (IF) or time-restricted rating (TRE) limits the eating window, leading to weight and fat loss, better cardiovascular health, and improved glucose tolerance, also influencing gut microbiota and metabolic processes.
Novel medications for weight loss
Effective pharmaceuticals for weight loss have long been sought due to the limitations of dietary interventions for obesity. Older drugs such as fenfluramine/phentermine had severe side effects, and gastrointestinal issues limited alternatives like orlistat and phentermine/topiramate. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for T2D, have shown promise in weight management by slowing gastric emptying and increasing satiety, achieving up to 15% weight loss in people with T2D and obesity. However, long-term efficacy and side effects are still unclear, with significant variation in patient responses. The gut microbiome, known to influence GLP-1 secretion, may contribute to these outcomes. Studies in mice suggest that GLP-1 agonists like liraglutide can increase A. muciniphila counts, enhancing GLP-1 release, although results vary based on baseline gut microbiota.
Updating the energy balance paradigm
The microbiome profoundly impacts nutrition and energy balance, influencing both caloric intake and expenditure. Gut microbes are known to ferment indigestible carbohydrates into short-chain fatty acids (SCFAs), contributing to energy salvage. Advances in sequencing and bioinformatics have expanded our understanding of the gut microbiome's role in digestion and metabolism. Studies show that the gut microbiome affects obesity, undernutrition, and metabolic health through various mechanisms, including SCFA production, microbial interaction with dietary compounds, and modulation of host energy metabolism. Additionally, the gut microbiome's influence on nutrient absorption, immune response, and metabolic diseases highlights its importance in human health.
Challenges the microbiome poses to nutrition
The microbiome challenges nutritional science by revealing complexities in caloric value, emphasizing the significance of unabsorbed nutrients, and questioning the safety of substances generally regarded as safe (GRAS). The gut microbiota's interactions with diet can significantly impact energy balance, health, and disease, necessitating a reevaluation of nutrition guidelines.
Conclusion and outlook
In summary, conventional nutritional wisdom, emphasizing balanced caloric intake, physical activity, and plant-based diets, remains relevant, but recent advances have transformed our understanding. The rise in obesity has shifted focus to dietary patterns like Mediterranean, ketogenic, and time-restricted eating, highlighting the gut microbiome's role in metabolism. While diet majorly influences the microbiome, other factors like pharmaceuticals and lifestyle choices also play significant roles. Precision nutrition, which leverages machine learning and rigorous human studies, aims to personalize dietary recommendations based on microbiome interactions, promising improved health outcomes and more reliable dietary advice in the future.
How a ketogenic diet could reduce autoimmune disease severity through host-microbiome interactions