In a review recently published in the journal cell, The 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. In addition, they explored emerging dietary patterns and the implications of microbiome research for nutrition.
Review: Complex metabolic effects of diet on the host and digesting microbiome. Image Credit: FOTOGRIN / Shutterstock
Background
Over the past 50 years, molecular nutrition has evolved from a focus on micronutrients to the study of macronutrients and dietary patterns, particularly due to the rise of 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 tailors 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 shown that microbiome data can be incorporated to improve metabolic health outcomes. However, more research is needed to validate precision nutrition and integrate it into clinical practice.
This review focuses on recent advances in diets, energy balance, and the gut microbiome, excluding discussion of dietary sugars, plant-based diets, genetically modified organisms (GMO), and undernutrition. . The authors aim to demonstrate rapid progress and general concepts relevant to other areas of nutrition research.
Emerging dietary interventions
Recent developments in human nutrition challenge traditional guidelines for fat restriction, including diets with moderate and 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, resistance insulin. , and inflammation, lowering mortality and risks of type 2 diabetes (T2D) and cancer. 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), which is very low in carbohydrates and high in fat, offers some weight loss and improved glycemic control but has potential disadvantages such as cardiovascular risks, nutritional 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 and maintaining nutrition extends lifespan, improves health, reduces fat, and improves insulin sensitivity, with gut microbiota changes mediating these benefits in mice, although human causal links remain unconfirmed. Intermittent fasting (IF) or time-restricted fasting (TRE) limits the eating window, resulting in weight and fat loss, better cardiovascular health, and improved glucose tolerance, also affecting 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 serious side effects, while gastrointestinal issues limited other options 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 satiety, achieving weight loss of up to 15% in people with T2D and obesity. However, efficacy and long-term side effects remain unclear, with significant variability in patient responses. The gut microbiome, which is known to influence GLP-1 secretion, may contribute to these findings. Studies in mice suggest that GLP-1 agonists such as liraglutide can increase A. muciniphila count, improving GLP-1 release, although results vary based on baseline gut microbiota.
Updating the energy balance paradigm
The microbiome has a major impact on nutritional and energy balance, and influences caloric intake and expenditure. Gut microbes are known to ferment indigestible carbohydrates into short-chain fatty acids (SCFAs), which contribute to energy conservation. Advances in sequencing and bioinformatics have increased our understanding of the role of the gut microbiome 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. In addition, the impact of the gut microbiome on nutrient absorption, immune response, and metabolic disease underscores its importance to human health.
The microbiome poses a challenge to nutrition
The microbiome challenges nutritional science by revealing the complexities of caloric value, emphasizing the importance of unabsorbed nutrients, and questioning the safety of substances generally considered safe (GRAS). Interactions of the gut microbiome with diet can have profound effects on energy balance, health and disease, necessitating a reevaluation of dietary guidelines.
Conclusion and perspective
In summary, conventional nutritional wisdom, emphasizing balanced caloric intake, physical activity, and plant-based diets, is still relevant, but recent advances have revolutionized our understanding. The rise in obesity has focused on dietary patterns such as the Mediterranean, ketogenic and time-limited diets, which emphasize the role of the gut microbiome in metabolism. While diet has a major impact on the microbiome, other factors such as medications and lifestyle choices play a significant role. Precision nutrition, leveraging machine learning and intensive human studies, aims to personalize dietary recommendations based on microbiome interactions, promising improved health outcomes and more reliable nutritional advice in the future.