When talking about body fat regulation we always have to adhere to the basic laws of thermodynamics. We know that increases in body fat mass happens when energy intake is higher than energy expenditure, and that we have to either decrease energy intake, increase energy expenditure, or both in order to lose weight. This basic fact has led many to believe that weight loss is all about eating less and/or exercising more. However, what we also have to account for is that the body is not a passive vehicle that just comes along for the ride. We already know that carbohydrates, fats, and proteins have a different thermic effect in the body and thereby differentially influence energy expenditure. We also know that food choices and diet composition have an impact on hormone levels, inflammatory processes, gut microbiota, reward centers in the brain, etc. and can thereby influence appetite, energy intake, and energy expenditure.
Food reward hypothesis
Some calorie-dense and highly palatable foods, such as pastries, pizza, hamburgers, and other common products in the western diet, are generally considered more fattening than simple, whole foods such as meat, vegetables, and fruits. But why is it so? If body fat regulation is all about energy in vs. energy out, it shouldn’t really matter what we eat as long as we don’t consume more calories than we need to sustain bodyweight. However, since dietary choices can impact both energy intake and energy expenditure through several mechanisms, we know that simply talking about calories is too simplistic.
Many processed westernized foods are hyper-rewarding in the sense that they contain a potent combination of sugar, salt, starch, fat, glutamate, and/or other food ingredients that in combination can overwhelm the reward center in our brain (1,2). Food manufacturers know how to use these hard-wired mechanisms to their advantage and hire scientists to design products that we essentially become addicted to (3). From an evolutionary perspective, there’s no doubt that these foods are novel introductions in the human diet. Hunter-gatherer and some traditional, non-westernized populations eat primarily simple, whole foods, and the absence of westernized food in these populations can help explain the extremely low obesity rates in these cultures.
This idea, that highly rewarding processed foods causes us to overeat and are the major driver of the obesity epidemic has been labelled the “food reward hypothesis.” At this point there are several studies supporting this hypothesis, and many obesity researchers consider food reward to be the primary player in the obesity epidemic. Essentially, the food reward hypothesis suggests that the reason we eat more calories than we need to sustain bodyweight is because these highly palatable, processed foods cause us to overeat (4).
Another important player that has emerged over the last decade is the human microbiome. Just like the food reward theory, this hypothesis is based on the idea that there are some factors about the modern obesogenic environment that cause us to store more fat. This goes back to the original premise, the gene-environment mismatch we’re now facing in the modern industrialized world is the fundamental cause of the obesity epidemic. Also, just like the food reward hypothesis, the microbiome hypothesis focuses on the western dietary pattern and the impact highly processed foods have on our health. However, here the focus is primarily on the changes these diets promote in our gut, not the impact they have on our brain. Also, the microbiome hypothesis stretches far beyond just diet.
It’s well established that a refined western diet promotes changes in the bacterial communities in the gut, which contributes to weight gain (5). However, we know that many aspects of our lifestyle other than diet impact the human microbiome. Antibiotics are routinely used in livestock to fatten animals up, and studies in humans have also linked antibiotic exposure in childhood to fatness later in life (6,7) . Some researchers have even proposed that the obesity epidemic in the U.S. could be partially driven by the use of antibiotics in livestock, which reach humans through food (8). Also, caesarean section and bottle feeding in infancy have been linked to being overweight later in life (9,10). Other factors, such as microbial exposures, microbial ecosystems in the home, and microbes inherited from mum, probably also play a role, but these things are harder to measure in scientific studies.
How can gut microbes affect body weight regulation?
How is it that these critters in our gastrointestinal tract are able to influence body fat regulation? Most of the early studies on the gut microbiome and obesity focused on the role gut bacteria play in energy harvesting. Essentially, it was believed that the “obese” gut microbiota extracted more energy from food and that this elevated energy acquisition was the reason for increased fat storage. However, what we’re now learning is that although this energy extraction probably does play a role, the small difference in energy acquisition can only account for some of the difference between the lean and obese microbiota. Many more theories have appeared, but a common theme is inflammation (11,12,13).
The gut microbiota controls the absorption of luminal content from the gut into systemic circulation by regulating intestinal barrier function, and this mechanism could help explain why gut bacteria play such an important role in immunity and inflammatory processes in the body. Microbes in the large intestine ferment indigestible food components (to the human host) and produce short-chain fatty acids. These fatty acids are the primary fuel for the colonocytes lining the large intestine and have been shown to regulate the differentiation and expansion of several types of T cell in the gut (14). This effect on immunological homeostasis is believed to be one of the key reasons gut microbes play such an important role in human health.
We know that obesity increases the risk of colon cancer, type-2 diabetes, cardiovascular disease, and a wide range of other inflammatory disorders. We also know that these conditions often go hand in hand with alterations in the gut microbiota and that these perturbations play an important role in the pathogenesis of these disorders. This suggests that one of the reasons obese people have a higher risk of many diseases is because they have an altered gut microbiota, which often harbor more proinflammatory microbes.
However, it’s not just microbes in the large intestine that have a significant impact on our health. The small intestine also harbors complex microbial communities, and one of the most interesting hypotheses related to the gut microbiome and obesity revolves around these critters. Ian Spreadbury (PhD), at the Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario, Canada, has written a paper where he hypothesizes that refined carbohydrates change the balance of microbes that live in the small intestine and that these alterations promote fat gain (15).
Spreadbury suggests that dense sources of carbohydrates in the western diet, such as refined grains and products high in sugar, promote the growth of proinflammatory bacteria in the gut. This process probably happens in the small intestine, but could also involve the colon. Some of these overgrowing gut microbes contain a substance called lipopolysaccharide, an endotoxin found in the outer wall of gram negative bacteria. Increased translocation of these bacterial toxins promote a state of endotoxemia, and in combination with other compounds that are allowed to enter systemic circulation, this increased intestinal permeability results in a state of low-grade chronic inflammation. Spreadbury’s theory is that this low-grade inflammation is the primary cause of leptin resistance, a hallmark of the obese state.
Leptin is one of the master hormones involved in long-term fat regulation, as leptin is part of a negative feedback loop between fat cells and the brain. Leptin is secreted by fat cells, and since leptin production correlates with the size of the fat stores, people who are obese produce a lot more leptin than those who are lean. This increased leptin production is supposed to trigger the brain to increase the use of stored energy and decrease food seeking behaviour. However, obesity is characterized by a state of leptin resistance, a condition where leptin doesn’t produce a sufficient signal in the brain (16). So, although folks who are obese have a lot of circulating leptin in their system, the brain thinks they carry much less body fat than they actually do and therefore defends an elevated amount of fat mass. Spreadbury suggests that this elevated body fat set point (more of a range) is the reason people who are obese homeostatically guard their elevated weight.
Spreadbury’s theory focuses on acellular carbohydrates in the western diet. While ancestral sources of carbohydrates, such as fruits, vegetables, and tubers are made up of living cells and contain a maximum density of around 23% carbohydrate, acellular carbohydrates, such as refined grains and products with a lot of sugar, contain a higher carbohydrate density than anything we’ve been eating throughout most of our evolutionary history. In combination with fatty foods, Spreadbury suggests that these acellular carbohydrates are the primary cause of leptin resistance and obesity.
Leptin wasn’t discovered until 1994, but is today considered one of the key hormones involved in obesity. Many theories have been proposed as to why individuals who are overweight and obese have decreased leptin sensitivity and how leptin resistance can be treated. However, Spreadbury’s theory is especially interesting as it focuses on the recent information on the human microbiome and suggests a mechanism that is consistent with a lot of other data. Spreadbury begins his article by highlighting the fact that studies unanimously show that hunter-gatherer populations have very low incidence of obesity and other diseases of civilization. Since these traditional populations consume/consumed widely different diets, he suggests that neither glycemic index, altered fat, nor carbohydrate intake can be the primary cause of the obesity epidemic. He also makes the case that the human energy homeostasis functions properly in the absence of westernized foods.
We already know that a diet rich in sucrose changes the oral microbiota and increases the risk of tooth decay and gingivitis (15). It’s therefore not unreasonable to suggest that this mechanism could also involve the small intestine. In general, Spreadbury’s theory is in line with other hypotheses which suggest that the obese microbiota increases low-grade chronic inflammation and that this inflammation sets the stage for leptin and insulin resistance. One of the things we don’t know at this point is whether this inflammatory process originates from the small or large intestine.
The microbiome-gut-brain axis
Some researchers have even hypothesized that the connection between diet and gut microbes also involve the brain, in the sense that there’s a positive feedback loop between the gut microbiota and areas in the brain that control food seeking behaviour (17). This hypothesis suggests that a high consumption of a specific food ingredient (e.g., sucrose) leads to the growth of certain species of microorganisms in the gut, which in turn affects our brain and increases our desire for foods that promote their growth and survival. The enteric nervous system in our gut is often considered the second brain in our body, a system that sends and receives impulses and can affect our mood and mental state. However, we’re now learning that the gut microbiota is also an important part of the intricate feedback system between the gut and the brain. The fact that gut microbes produce neurotransmitters and other substances that act on various brain regions have led to the expansion of the gut-brain axis into the microbiome-gut-brain axis (18,19).
The microbiome-gut-brain axis is very relevant in terms of obesity because it could mean that the link between diet and weight regulation is more intricate than we’ve realized. If it does hold true that gut microbes impact the brain in a way as to regulate our food preferences and appetite, obesity could be a vicious cycle where a western-type diet promotes weight gain and alterations in the gut microbiota, and these changes in the bacterial communities in the gut then induce an increased desire for foods that promote a gut environment in which certain microbes can thrive.
There’s definitely more work to be done on this hypothesis, but it’s a very interesting idea that could partially explain many common phenomenons, such as the reason some people are drawn towards certain foods again and again and why some foodstuff that have been shown to have a significant impact on our gut microbiota (e.g., chocolate) often can be addictive. To which extent this positive feedback mechanism really is involved in controlling our dietary preferences remains to be elucidated, but from what we now know it can be hypothesized that one of the benefits of manipulating the obese microbiome is that we alter the signals that go through this microbiome-gut-brain axis.
Food reward and the human microbiome are key players in the obesity epidemic
Both the food reward and the human microbiome probably play an important role in the obesity epidemic. While most of the focus among obesity researchers has been on food reward, the expanding area of microbiome research has also led many to open their eyes to the idea that the microbial ecosystems in our body play an important role in obesity. Both of these theories are consistent with two key things we know about obesity:
1) Weight gain results from an imbalance between energy intake and energy expenditure. The food reward hypothesis suggests that the reason we consume more energy than we need to sustain bodyweight is because highly rewarding modern foods overwhelm the reward center in the brain and trigger us to overeat. There are many theories as to how gut microbes can affect weight regulation. They can increase energy extraction from food and also indirectly impact fat storage by affecting hormone sensitivity, inflammation, and other factors that researchers are just beginning to explore. Both hypotheses could include a mechanism where obesity is a vicious cycle. The food reward hypothesis says that highly rewarding foods trigger addictive processes in the brain, while the microbiome hypothesis says that diet impacts gut microbiota composition and gut microbiota affects dietary preferences.
2) Obesity is a disease of civilization . The food reward hypothesis is based on the idea that westernized foods are a primary driver of the obesity epidemic, and this hypothesis is therefore consistent with the observation that obesity is a disease of civilization. The microbiome hypothesis suggests that several aspects of the western lifestyle (e.g, western dietary pattern, antibiotics) perturb the gut microbiome, which triggers fat gain. This hypothesis is therefore consistent with the observation that obesity is a disease of civilization.
Next: Are Gut Bacteria Making You Fat? Part IV: Wrapping It Up
Like this article? For more great content, delivered right to your door (and tablet, phone & computer!) subscribe to Paleo Magazine now!