Not too long ago, we thought we understood nutrition. Food could be broken down to its component parts: carbohydrates, protein, and fat along with micronutrients such as iron and vitamins. Dietary advice was based on calculations of our body’s needs for these nutrients. Malnutrition could be eliminated by meeting recommended dietary allowances in each of these nutrient categories. Obesity could be avoided by calculating energy requirements, paying attention to serving sizes, and exerting self control. Simple and scientific, right?

Now we know it is not so simple. We had overlooked a hugely important factor in nutrition and metabolism, the microbiota.  The microbiota consists of at least 30 trillion cells, including bacteria, archaea, and fungi, that inhabit our bodies. These weigh about 2 kilograms (4 1/2 pounds) and can be found mostly in the colon.   In the last 10 years, research on the gut microbiota is generating new findings at a breathtaking pace. This knowledge has upended the conventional wisdom on diet, nutrition, and obesity.

How important is the microbiota in nutrition? A compelling early piece of evidence came from experiments with germ-free mice.  Germ-free mice are delivered by cesarean section and carefully raised in a sterile laboratory environment so that they never contact microbes.  The germ free mice in this study were genetically predisposed to be obese, but the germ free ones stayed lean, even when they were fed a high fat diet. When the germ free mice came in contact with fecal matter from conventional mice (not germ free), they rapidly gained weight and became obese.  This meant that when it comes to fatness, diet alone was not enough. Microbes in combination with diet were necessary to cause overweight and obesity.

Some scientists thought that gut microbes cause weight gain because they help us extract extra calories from our diet. This explanation has some truth to it, but this mechanism is not responsible for the current epidemic of obesity.  Gut microbes also cause obesity by generating chronic low grade inflammation.  Inflammation happens when the gut microbiota undergoes unhealthy changes (dysbiosis) and when our bodies are unable to contain gut microbes to where they belong – inside the intestine.

Inflammation can happen after a single meal. When human volunteers ate a high fat meal that contained cream and glucose, endotoxin from gut bacteria spiked in the blood within an hour. Endotoxin is an integral building block of  bacterial cell walls. When it appears in the blood, endotoxemia  promptly activates immune cells, causing inflammation. Chronic inflammation caused by gut microbes is thought to play a role in many  diseases: obesity, diabetes, atherosclerosis, high blood pressure, and heart disease. Obesity, in particular, is accelerating in many populations. Since gut microbes are involved, they provide a key to stopping the obesity epidemic.

One possible solution is a dietary strategy that focuses on the gut microbiota. This is possible because nutrients have different, often opposite effects on gut microbes and inflammation. In the study cited earlier, orange juice, consumed at the same time as a high fat, high calorie meal,  prevented endotoxin from entering the blood and blocked inflammation. These results were an early clue that not all calories are equal. Foods that cause dysbiosis and low-grade inflammation can be substituted for other foods that prevent inflammation. Despite having a lot of calories, orange juice has been shown to block fat accumulation in mice, and is associated with healthy body composition in humans. The microbiota is the missing piece of the puzzle. We need to pay attention to calories and food labels, and we need to understand how food choices affect the microbes in our guts.

Since the research with orange juice was done, additional research has identified other foods that prevent inflammation and possible harmful changes to our metabolism. These include anti-inflammatory fats, including shorter chain fatty acids and omega-3 fatty acids. These anti-inflammatory fats inhibit harmful microbial growth and may protect against dysbiosis and leaky gut. Plant polyphenols and flavonones, like hesperin and naringen in orange juice, have similar beneficial effects in the gut. One beneficial effect of healthy fats and plant polyphenols is their ability to work in concert with the human immune system to keep harmful microbes in check. These nutrients shape the microbiome, in tandem with the immune system, so that we are protected from inflammation from endotoxin.

A recent randomized controlled trial examined how yogurt affects the immune response in healthy human volunteers. 69 obese and 60 non-obese women were assigned to consume soy or a low fat yogurt. The yogurt consumption was associated with reduced inflammatory biomarkers and reduced endotoxin and lower LPS binding protein in the blood of subjects after 9 weeks. Yogurt contains live bacteria, and so it is both food and probiotic. The human results in this study are consistent with a variety of animal studies showing salutary effects of probiotics on microbiome, gut barrier function, visceral fat, and inflammation.

Nutritionists generally agree that what we eat – the Western diet – is too low in fiber, vegetables, and too high in refined sugar and unhealthy fats. As we have described in this blog,  the Western diet is unhealthy also because it negatively affects the composition of the microbiome. Our energy dense low-fiber diets also cause disease because natural selection has shaped pro-inflammatory responses to various nutrients. Nutrient signaling is the hypothesis that diet encodes signals that evolved because nutrients predictably shape the microbiome and influence the risk of infection.  This evolutionary hypothesis that may illuminate the predictive relationship between diet, food, and microbiome, has been described on this blog, here, here, and here.

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine