In a recent review published in the journal Cell, The researchers discussed recent advances in molecular nutrition, focusing on pharmaceutical and dietary interventions to manage energy balance and their interactions with the gut microbiome in humans. Furthermore, they explored emerging dietary patterns and the nutritional implications of microbiome research.
Review: Digesting the complex metabolic effects of nutrition on the host and microbiome. Image Credit: FOTOGRIN / Shutterstock
Background
Over the last 50 years, molecular nutrition has evolved from a focus on micronutrients to examining macronutrients and dietary patterns, particularly due to the rise in obesity. A growing body of evidence highlights 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 Diet Composition Trial (PREDICT) have demonstrated the potential of incorporating microbiome data to improve metabolic health outcomes. However, more research is needed to validate and integrate precision nutrition into clinical practice.
The current review focuses on recent developments in the field of diets, energy balance, and the gut microbiome, excluding discussions on dietary sugars, plant-based diets, genetically modified organisms (GMOs), and malnutrition. The authors aim to illustrate the rapid progress and general concepts applicable to other areas of nutrition research.
Emerging dietary interventions
Recent advances in human nutrition are challenging traditional fat restriction guidelines by 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, and in reducing mortality and the risk of type 2 diabetes (T2D) and cancer. Its mechanisms include lipid lowering, oxidative stress protection, and nutrient-sensing pathway inhibition. MD positively impacts the gut microbiome, increasing fiber-degrading taxa and beneficial metabolic phenotypes. The ketogenic diet (KD), which is very low in carbohydrates and high in fat, provides modest weight loss and improved glycemic control but has potential drawbacks, including cardiovascular risks, nutrient deficiencies, and harmful gut bacterial metabolites. The KD uniquely alters the gut microbiota and protects against seizures and autoimmune diseases in a microbiota-dependent manner. Caloric restriction (CR), reducing dietary intake while maintaining nutrition, extends lifespan, improves healthy lifespan, reduces fat, and increases insulin sensitivity; changes in gut microbiota mediate these benefits in mice, but human causal links have not been confirmed. Intermittent fasting (IF) or time-restricted cycling (TRE) leads to weight and fat loss by limiting the eating window, better cardiovascular health, and improved glucose tolerance, and also affects gut microbiota and metabolic processes.
New drugs for weight loss
Because of the limitations of dietary interventions for obesity, effective drugs for weight loss have long been sought. Older drugs such as fenfluramine/phentermine had serious side effects, and gastrointestinal issues limited alternatives such as orlistat and phentermine/topiramate. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for T2D, have shown promise in weight management by slowing gastric emptying and increasing feelings of fullness, resulting in up to 15% weight loss in people with T2D and obesity. However, long-term efficacy and side effects are still uncertain, and there is considerable variability in patient responses. The gut microbiome, known to influence GLP-1 secretion, may contribute to these results. Studies in mice have shown that GLP-1 agonists such as liraglutide A. muciniphila It increases counts by increasing GLP-1 release, although results vary depending on baseline gut microbiota.
Updating the energy balance paradigm
The microbiome profoundly influences nutrition and energy balance by influencing both calorie intake and expenditure. Gut microbes are known to contribute to energy recovery by fermenting nondigestible carbohydrates into short-chain fatty acids (SCFAs). Advances in sequencing and bioinformatics have expanded our understanding of the role of the gut microbiome in digestion and metabolism. Studies suggest that the gut microbiome influences obesity, malnutrition, and metabolic health through a variety of mechanisms, including SCFA production, microbial interactions with dietary components, and modulation of host energy metabolism. Additionally, the impact of the gut microbiome on nutrient absorption, immune response, and metabolic diseases underscores its importance in human health.
The challenges the microbiome poses to nutrition
The microbiome challenges nutritional science by revealing complexities in caloric value, highlighting the importance of unabsorbed nutrients, and questioning the safety of substances generally recognized as safe (GRAS). The interactions of the gut microbiota with the diet can significantly impact energy balance, health, and disease, necessitating a reevaluation of dietary guidelines.
Conclusion and outlook
In summary, conventional nutritional wisdom emphasizing balanced caloric intake, physical activity, and plant-based diets remains valid, but recent developments have transformed our understanding. The rise in obesity has shifted focus to dietary patterns such as Mediterranean, ketogenic, and time-restricted diets, and has emphasized the role of the gut microbiome in metabolism. While diet greatly influences the microbiome, other factors such as medications and lifestyle choices also play important roles. Using machine learning and rigorous human studies, precision nutrition aims to provide personalized dietary recommendations based on microbiome interactions, promising better health outcomes and more reliable dietary recommendations in the future.