How diet affects the body and its microbiota

A deeper understanding of human biology, new dietary and medical interventions, and their effects on the microbiota may lead to more accurate and trustworthy dietary advice.
Table of Contents

What is already known
Over the past 50 years, our understanding of human nutrition has changed, holding promise for personalized dietary advice to improve a person’s health. For example, advances in DNA sequencing helped to develop personalized dietary recommendations based on a person’s genetic profiles, and studies in both model organisms and humans have shown that an individual’s gut microbiota influences responses to different diets.

What this research adds
The authors discuss recent advances in molecular nutrition — a field that explores how diet impacts the body at the molecular level. They also examine the connections between diet, gut microbes and host metabolism.

Conclusions
A deeper understanding of human biology, new dietary and medical interventions, and their effects on the microbiota may lead to more accurate and trustworthy dietary advice.

Over the past 50 years, our understanding of human nutrition has changed, holding promise for personalized dietary advice to improve a person’s health.

In a review published in Cell, Rachel Carmody at Harvard University in Cambridge, Massachusetts, and her colleagues discuss recent advances in molecular nutrition — a field that explores how diet impacts the body at the molecular level. They also examine the connections between diet, gut microbes and host metabolism.

In the past two decades, advances in DNA sequencing helped to develop personalized dietary recommendations based on a person’s genetic profiles, and studies in both model organisms and humans have shown that an individual’s gut microbiota influences responses to different diets.

In particular, four dietary interventions that do not require strict limits on fat intake — the Mediterranean diet, the ketogenic diet, calorie restriction and intermittent fasting — have been shown to affect the gut microbiota, although the underlying mechanisms remain unclear.

Dietary interventions

The Mediterranean diet emphasizes minimally processed whole grains, legumes, fruits, vegetables, nuts, seeds and olive oil. This diet can help reduce body weight, blood pressure, cholesterol levels and inflammation, as well as the risk of type 2 diabetes and certain cancers. The diet also promotes beneficial gut bacteria, but clear links with specific microbes remain elusive. 

Low-carbohydrate, high-fat ketogenic diets can lead the body to burn fat to produce energy. Originally used to treat epilepsy, ketogenic diets are now explored for their potential benefits in managing type 2 diabetes and weight loss. Research suggests that these diets can alter the gut microbiota and their metabolites. 

Daily calorie restriction can increase lifespan, reduce body weight, and improve blood pressure and cholesterol levels. Studies in animal models showed that changes in gut bacteria contribute to weight loss, but human studies have shown mixed results.

Finally, intermittent fasting, which involves limiting eating to a 4 to 10-hour window each day, can lead to reduced body weight and improvements in some cardiovascular health markers. This dietary intervention also affects the gut microbiota, but the exact mechanisms are still unclear.

Energy balance

Recent advances in high-throughput sequencing, bioinformatics and animal models have allowed researchers to discover that diet plays a more significant role than genetics in shaping the composition and function of the gut microbiota.

Gut microbes play a crucial role in energy balance, with studies showing that colonizing germ-free mice with conventional microbiota can increase body fat despite lower food intake. Other studies have shown that gut microbes from lean people can mitigate obesity, while those from obese people can promote fat gain. 

Most research on how gut microbes influence human metabolism has focused on their ability to turn carbohydrates into short-chain fatty acids (SCFAs), which serve as energy sources. SCFAs can also affect appetite by crossing the blood-brain barrier, and they influence energy expenditure by boosting the function of mitochondria — the cell’s powerhouses.

An additional mechanism through which the gut microbiota affects host metabolism is through the production of metabolites such as trimethylamine N-oxide (TMAO) — a compound that has been associated with atherosclerosis and thrombosis. Gut microbes also modify bile acids, influencing lipid metabolism and energy balance, and ferment dietary protein to produce compounds that have been linked to metabolic and gut disorders. 

Managing human nutrition

Growing evidence shows that unabsorbed nutrients, which reach the gut microbiota in the colon, can play a crucial role in health and disease by influencing the gut microbiota and its effects on the host. 

Recent research has also revealed that emulsifiers and artificial sweeteners alter the gut microbiota in ways that could induce obesity and insulin resistance. Similarly, compounds such as taurine can lead to gut disorders. However, the gut microbiota can also produce beneficial effects, including converting dietary lignans, which are found in various plant-based foods, into cancer-protective compounds.

The complex interactions between diet, microbiota and health highlight the need for human studies and data-driven research to refine precision nutrition, the authors say. A deeper understanding of human biology, new dietary and medical interventions, and their effects on the microbiota may lead to more accurate and trustworthy dietary advice, they add. “Such data-driven targeting of the microbiome and its interactions with diet will hopefully provide a rich new toolbox for managing human nutrition over the next 50 years.”