Is the adage “calories in, calories out” true? The short answer is yes, but the full story is more nuanced.

From the moment food touches your tongue to the time it leaves your body, your digestive system and gut microbiome work to extract its nutrients. Enzymes in your mouth, stomach and small intestine break down food for absorption, while microbes in your large intestine digest the leftovers.

“Calories in, calories out” refers to the concept that weight change is determined by the balance between the calories you consume and calories you expend. This includes not only the number of calories you eat due to appetite and absorb via digestion, but also how well those absorbed calories are burned through metabolism.

Recent research indicates that a significant factor influencing people’s variable appetites, digestion and metabolism are biologically active leftover components of food, known as bioactives. These bioactives play a key role in regulating the body’s metabolic control centers: your brain’s appetite center, the hypothalamus; your gut’s digestive bioreactor, the microbiome; and your cells’ metabolic powerhouses, the mitochondria.

I’m a gastroenterologist who has spent the past 20 years studying the gut microbiome’s role in metabolic disease. I’ll share how dietary bioactives help to explain why some people can eat more but gain less, and I’ll offer some dietary tools to improve metabolism.

Ruminating on appetite and digestion

Research has shown that consuming whole foods still “packaged” in their original fibers and polyphenols – the cellular wrappers and colorful compounds in plants that confer many of their health benefits – leads to more calories lost through stool, when compared with processed foods that have been “predigested” by factories into simple carbs, refined fats and additives.

This is one way calorie-free factors influence the “calories in, calories out” equation, which can be beneficial in a society where calorie intake often exceeds needs. Eating more whole foods and less processed foods simply lets you eat more because more of those unprocessed calories go out the other end unused.

Fiber and polyphenols also help regulate your appetite and calorie intake through the brain. Your microbiome transforms these leftover bioactives into metabolites – molecular byproducts of digestion – that naturally decrease your appetite. These metabolites regulate the same gut hormones that first inspired the popular weight loss drugs Wegovy, Ozempic and Mounjaro, controlling appetite through your brain’s satiety center, the hypothalamus.

Processed foods lack these bioactives and are further formulated with salt, sugar, fat and additives to be hyperpalatable, causing you to crave them and eat more.

Mitochondrial maestros in the middle

A full accounting of calories also depends on how effectively your body burns them to power your movement, thoughts, immunity and other functions – a process largely orchestrated by your mitochondria.

Healthy people typically have high-capacity mitochondria that easily process calories to fuel cellular functions. People with metabolic diseases have mitochondria that don’t work as well, contributing to bigger appetites, less muscle and increased fat storage.

They also have less of a mitochondria-rich type of fat called brown fat. Rather than storing calories, this fat burns them to produce heat. Less brown fat may help explain why some people with obesity can have lower body temperatures than those who aren’t obese, and why there has been a decline in average body temperature in the U.S. since the industrial revolution.

Healthy mitochondria that burn more calories might also help explain why some people can eat more without gaining weight. But this raises the question: Why do some people have healthier mitochondria than others?

Your mitochondrial health is ultimately influenced by many factors, including those usually associated with overall well-being: regular exercise, adequate sleep, stress management and healthy eating.

Who turned off the metabo-lights

The latest nutrition research is revealing the roles that previously underappreciated dietary factors play in mitochondrial health. Beyond the essential macronutrients – fat, protein and carbohydrates – and micronutrients such as vitamins and minerals, other leftover factors in food, including fibers, polyphenols, bioactive fats and fermentation products, are also key for metabolism.

Unlike a Western diet, which often lacks these bioactives, traditional diets such as the Mediterranean and Okinawan diets are rich in foods – nuts, seeds, fruits, vegetables, whole grains and fermented foods – replete with these factors. Many bioactives pass undigested through the small intestine to the large intestine, where the microbiome converts them into activated metabolites. These metabolites are then absorbed, influencing the number of mitochondria in cells and how they function.

At the most fundamental level of cell biology, metabolites turn on and off molecular switches in your genes through a process called epigenetics that can affect both you and your offspring. When the metabolic “lights” are turned on, they enliven the mitochondria responsible for a faster metabolism, effectively increasing the calories you use.

Please mind the microbiome gap

A healthy microbiome produces a full range of beneficial metabolites that support calorie-burning brown fat, muscle endurance and metabolic health. But not everyone has a microbiome capable of converting bioactives into their active metabolites.

Long-term consumption of processed foods, low in bioactives and high in salt and additives, can impair the microbiome’s ability to produce the metabolites needed for optimal mitochondrial health. Overuse of antibiotics, high stress and lack of exercise can also adversely affect microbiome and mitochondrial health.

This creates a double nutrition gap: a lack of healthy diet and a deficiency in the microbes to convert its bioactives. As a result, well-studied nutritional approaches such as the Mediterranean diet might be less effective in some people with an impaired microbiome, potentially leading to gastrointestinal symptoms such as diarrhea and negatively affecting metabolic health.

In these cases, nutrition research is exploring the potential health benefits of various low-carb diets that may bypass the need for a healthy microbiome. While the higher protein in these diets can reduce the microbiome’s production of beneficial metabolites, the lower carbs stimulate the body’s production of ketones. One ketone, beta-hydroxybutyrate, may function similarly to the microbiome metabolite butyrate in regulating mitochondria.

Emerging microbiome-targeting approaches might also prove helpful for improving your metabolic health: butyrate and other postbiotics to provide preformed microbiome metabolites, personalized nutrition to tailor your diet to your microbiome, intermittent fasting to help repair your microbiome, and the future possibility of live bacterial therapies to restore microbiome health.

Tools to transform fat into fuel

For most people, restoring the microbiome through traditional diets such as the Mediterranean diet remains biologically achievable, but it is not always practical due to challenges such as time, cost and taste preferences. In the end, maintaining metabolic health comes back to the deceptively simple healthy lifestyle pillars of exercise, sleep, stress management and nutritious diet.

Some simple tips and tools can nonetheless help make nutritious diet choices easier. Mnemonics such as the 4 F’s of food – fibers, polyphenols, unsaturated fats and ferments – can help you focus on foods that best support your microbiome and mitochondria with “leftovers.” Bioactive-powered calculators and apps can also aid in selecting foods to control your appetite, digestion and metabolism to rebalance your calorie “ins and outs.”

Christopher Damman, Associate Professor of Gastroenterology, School of Medicine, University of Washington

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Astronomers exploring the faraway universe with the James Webb Space Telescope, NASA’s most powerful telescope, have found a class of galaxies that challenges even the most skillful creatures in mimicry – like the mimic octopus. This creature can impersonate other marine animals to avoid predators. Need to be a flatfish? No problem. A sea snake? Easy.

When astronomers analyzed the first Webb images of the remote parts of the universe, they spotted a never-before-seen group of galaxies. These galaxies – some hundreds of them and called the Little Red Dots – are very red and compact, and visible only during about 1 billion years of cosmic history. Like the mimic octopus, the Little Red Dots puzzle astronomers, because they look like different astrophysical objects. They’re either massively heavy galaxies or modestly sized ones, each containing a supermassive black hole at its core.

However, one thing is certain. The typical Little Red Dot is small, with a radius of only 2% of that of the Milky Way galaxy. Some are even smaller.

As an astrophysicist who studies faraway galaxies and black holes, I am interested in understanding the nature of these little galaxies. What powers their light and what are they, really?

The mimicking contest

Astronomers analyze the light our telescopes receive from faraway galaxies to assess their physical properties, such as the number of stars they contain. We can use the properties of their light to study the Little Red Dots and figure out whether they’re made up of lots of stars or whether they have a black hole inside them.

Light that reaches our telescopes ranges in wavelength from long radio waves to energetic gamma rays. Astronomers break the light down into the different frequencies and visualize them with a chart, called a spectrum.

Sometimes, the spectrum contains emission lines, which are ranges of frequencies where more intense light emission occurs. In this case, we can use the spectrum’s shape to predict whether the galaxy is harboring a supermassive black hole and estimate its mass.

Similarly, studying X-ray emisson from the galaxy can reveal a supermassive black hole’s presence.

As the ultimate masters of disguise, the Little Red Dots appear as different astrophysical objects, depending on whether astronomers choose to study them using X-rays, emission lines or something else.

The information astronomers have collected so far from the Little Red Dots’ spectra and emission lines has led to two diverging models explaining their nature. These objects are either extremely dense galaxies containing billions of stars or they host a supermassive black hole.

The two hypotheses

In the stars-only hypothesis, the Little Red Dots contain massive amounts of stars – up to 100 billion stars. That’s approximately the same number of stars as in the Milky Way – a much larger galaxy.

Imagine standing alone in a huge, empty room. This vast, quiet space represents the region of the universe in the vicinity of our solar system where stars are sparsely scattered. Now, picture that same room, but packed with the entire population of China.

This packed room is what the core of the densest Little Red Dots would feel like. These astrophysical objects may be the densest stellar environments in the entire universe. Astronomers aren’t even sure whether such stellar systems can physically exist.

Then, there is the black hole hypothesis. The majority of Little Red Dots display clear signs of the presence of a supermassive black hole in their center. Astronomers can tell whether there’s a black hole in the galaxy by looking at large emission lines in their spectra, created by gas around the black hole swirling at high speed.

Astronomers actually estimate these black holes are too massive, compared with the size of their compact host galaxies.

Black holes typically have a mass of about 0.1% of the stellar mass of their host galaxies. But some of these Little Red Dots harbor a black hole almost as massive as their entire galaxy. Astronomers call these overmassive black holes, because their existence defies the conventional ratio typically observed in galaxies.

There’s another catch, though. Unlike ordinary black holes, those presumably present in the Little Red Dots don’t show any sign of X-ray emission. Even in the deepest, high-energy images available, where astronomers should be able to easily observe these black holes, there’s no trace of them.

Few solutions and plenty of hopes

So are these astrophysical curiosities massive galaxies with far too many stars? Or do they host supermassive black holes at their center that are too massive and don’t emit enough X-rays? What a puzzle.

With more observations and theoretical modeling, astronomers are starting to come up with some possible solutions. Maybe the Little Red Dots are composed only of stars, but these stars are so dense and compact that they mimic the emission lines typically seen from a black hole.

Or maybe supermassive – even overmassive – black holes lurk at the cores of these Little Red Dots. If that’s the case, two models can explain the lack of X-ray emissions.

First, vast amounts of gas could float around the black hole, which would block part of the high-energy radiation emitted from the black hole’s center. Second, the black hole could be pulling in gas much faster than usual. This process would produce a different spectrum with fewer X-rays than astronomers usually see.

The fact that the black holes are too big, or overmassive, might not be a problem for our understanding of the universe, but rather the best indication of how the first black holes in the universe were born. In fact, if the first black holes that ever formed were very massive – about 100,000 times the mass of the Sun – theoretical models suggest that their ratio of black hole mass to the mass of the host galaxy could stay high for a long time after formation.

So how can astronomers discover the true nature of these little specks of light that are shining at the beginning of time? As in the case of our master of disguise – the octopus – the secret resides in observing their behavior.

Using the Webb telescope and more powerful X-ray telescopes to take additional observations will eventually uncover a feature that astronomers can attribute to only one of the two scenarios.

For example, if astronomers clearly detected X-ray or radio emission, or infrared light emitted from around where the black hole might be, they’d know the black hole hypothesis is the right one.

Just like how our marine friend can pretend to be a starfish, eventually it will move its tentacles and reveal its true nature.

Fabio Pacucci, Astrophysicist, Smithsonian Institution

This article is republished from The Conversation under a Creative Commons license. Read the original article.