Who controls our appetite: us or bacteria?
The sensations of hunger and satiety mobilize every animal. And both sensations are of visceral origin. In other words, our digestive tract commands our energy behavior through molecules that interact with our brain and, this, integrates the signals that give as a response: I need food (hunger) or I am satisfied (satiety).
For a few years now, the scientific community has been echoing the role of what we name the forgotten organ, our intestinal microbiota. This ecosystem of microbes lives in symbiosis with us and requires energy to carry out its biological processes. In other words, it depends on what we eat to provide it with a substrate for its life in balance. Don’t you think, then, that our bacteria can modify our behavior of hunger and satiety? Or put similarly: who commands our appetite: our needs or theirs? Science has been questioning it for a very short time and it seems that the first results indicate that they send more than us.
Gut Bacterial Proteins May Influence Appetite Control
In fact, several studies have revealed that there is a bacterial dysbiosis in obesity and anorexia nervosa, suggesting a causal role of intestinal bacteria in the altered regulation of energy metabolism and, possibly, in eating behavior. A recent study published in 2016 revealed that gut bacterial proteins can influence bacterial growth phase-dependent appetite control.
Network of neurons
If we look at how appetite pathways are structured in the brain, we will see that these pathways are organized around circumventricular organs – such as the arcuate nucleus of the hypothalamus (ARC) and the nucleus tractus solitarius (NTS) -. Both ARC and NTS neurons project to other hypothalamic, brainstem, and forebrain regions, forming a neural network. Among these regions, important roles have been attributed to the hypothalamic (PVN) and ventromedial (VMN) paraventricular nuclei, the lateral hypothalamic area (LHA) and the parabrachial area (PBN), as well as the central nucleus of the amygdala (CeA). As we will see, bacterial products can activate these areas, influencing appetite control.
This model assumes that the energy balance that controls the hypothalamic centers must be able to measure the available energy both in the short and long term, in order to satisfy immediate physiological energy needs and maintain the equilibrium point of body weight. However, this homeostatic model does not take into account the energy needs of the gut bacteria that are distinct from those of the host, and thus may independently affect the host’s control of appetite.
An abnormal hedonic drive to eat can override homeostatic signals
In addition, we must not forget the recent publications on the interaction of bacteria with the brain nuclei that form the dopaminergic reward circuit, such as the ventral tegmental area (VTA) and the nucleus accumbens (NA), and which give the hedonic value of eating. An abnormal hedonic drive to eat may override homeostatic signals and could be present in bulimia nervosa or potentially drive increased intake of energy-rich foods that cause obesity.
As dopaminergic neurons (AVT) are protected by the blood-brain barrier, the possible effects of circulating molecules derived from gut bacteria on this dopamine system should be transmitted through other neurons, such as those of the parabrachial nucleus (PBN).
Both homeostatic and hedonic systems that control appetite are activated by hormones derived from tissues and organs that signal various metabolic processes, including energy storage and nutritional status. This is where the enteroendocrine cells of the gastrointestinal tract that secrete various peptide hormones into the systemic circulation come into play. Among others, ghrelin, produced by the stomach being the only orexigenic hormone known to date, and anorexigenic hormones -such as cholecystokinin (CKK) and peptide tyrosine tyrosine (PYY)- produced in the small and large intestine and that induce satiety postprandial.
All of these hormones play important roles in short- and long-term appetite control. We will understand short-term appetite as responsible for the cyclical alternation of hunger and satiety on a daily basis. And long-term appetite as appetite changes over prolonged periods to meet new energy demands.
Similar to the molecular pathways that regulate energy metabolism in the host, the gut microbiota is also subject to both short- and long-term changes. Short-term daily changes include fluctuations in the number of bacteria, while long-term changes refer mainly to the composition of the microbiota.
Bacteria living in communities are capable of intrinsically regulating their growth. Under conditions of regular nutrient supply it takes 20 minutes for the number of bacteria to double. When they reach 109 per ml, they enter a stationary growth phase that maintains the number of bacteria for a few hours. The stationary phase is followed by the phase of decline due to cell lysis, which is characterized by a progressive decrease in the number of bacteria.
Apart from this intrinsic regulation, the growth of bacterial populations is constantly influenced by diet and limited by chemical production and physical factors. A balance between these factors determines the relative stability of a bacterial population in each part of the gastrointestinal tract.
Physical factors: peristalsis + contractions of the colon and rectum. Regular elimination of bacteria by defecation.
Chemical factors: gastric acids, bile juices and digestive enzymes.
For example, a standard fecal stool contains approximately 15 grams of bacteria, which is equivalent to 55% of the dry weight of the stool.
The constant dynamics of bacterial growth, lysis, and clearance maintain the intestinal bacterial population at a fairly stable level, indicating that both bacteria and host contribute to the maintenance of energy homeostasis in a population of intestinal bacteria.
Energy requirement of the intestinal microbiota
Intestinal bacteria make up a metabolically active organ weighing approximately 1-2kg in adult humans. Nutrient-induced bacterial growth in a large population, such as in the colon, results in a simple duplication of bacteria. And this duplication is very expensive energetically. To double 1 gram of bacteria, 1 Kcal is needed, therefore for the duplication of 1-2kg of bacteria, between 1,000 and 2,000 kcal will be needed, which is approximately half of the energy intake of an adult.
“Alterations in the dynamics of bacterial growth, for example those that result in bacterial overgrowth, are accompanied by an increase in the energy demand of gut bacteria, suggesting that it could lead to increased appetite in the host.”
The exchange of energy through the food chain represents a universal link between all organisms. The energy (in the form of ATP) produced by the intestinal bacteria is used not only for their own growth, but is also made available to the host. The bacteria release enzymes and metabolites that aid in the digestion of nutrients, including fiber, that are not digestible by the host. For example, E. coli proteins released after nutrient-induced bacterial growth can synthesize ATP that is used by the host. And the bacterial capacity for energy extraction depends on the individual composition of the intestinal microbiota. For example, during host starvation, gut bacteria receive nutrients only from the host, slowly depleting energy stores in fat, liver, and muscle.
Changes in bacterial composition during fasting will favor species that are better adapted to low energy supply, which helps the host to survive energy deprivation, which we could define as teamwork for survival both of them as of us.
To optimize this goal, the dynamics of bacterial growth must be synchronized with the host’s feeding behavior and the behavior of hunger and satiety.
“Consequently, a decrease in bacterial population size must be associated with starvation. Conversely, its stability with satiety”
As we showed in the book that we published a few months ago, Healthy Children, Healthy Adults from Editorial Platform, the greater the bacterial diversity, the greater the health and conversely, the less bacterial diversity, the more relationship with the disease. It would not be unreasonable to think that since the programming of the microbiota has been developed throughout its window of opportunity (pregnancy and early life) and all the factors that interact in this programming, it will also influence the behavior of hunger and satiety at an early age. and in adult life.
Why do we feel full 20 minutes after eating if the nutrients have not yet been digested or absorbed? It seems that there is a release of intestinal hormones of satiety such as GLP1 and PYY at 15-20 ‘post meal. Do we control our appetite or does our microbiota really do it?
This increase in secretory activity cannot be a consequence of direct stimulation of nutrient receptors on the surface of enteroendocrine cells by food ingestion, since several hours of intestinal transit are required in humans and rodents, during which time the Most nutrients are absorbed by the small intestine.
The only way for nutrients shortly after a meal to activate enteroendocrine cells in the distal GI tract is if they are delivered directly into the lumen of the intestine. That secretory reflex was discovered more than 100 years ago by Ivan Pavlov using false feeding in dogs. Pavlov proved that abundant intestinal secretion begins 1-3 minutes after a meal or its anticipation.
Molecules produced by bacteria can signal an energy balance to the host, which translates into a feeling of satiety
This activation of enteroendocrine cells will also trigger 20-minute bacterial growth in the large intestine, maintaining such growth in a stationary phase. This can last a few hours until reaching the decline phase, where there will be a bacterial lysis to always maintain a balance in the ecosystem.
It is in the stationary phase where the bacteria will produce molecules that can indicate an energy balance to the host, which becomes a feeling of satiety. On the contrary, in the phase of decline of the intestinal bacterial population it could be accompanied by a decrease of such stationary signals related to the phase, which is perceived by the host as an energy deficit and a sensation of hunger.
the energetic state of a bacterial population could therefore drive the alternative activation of hunger and satiety pathways.
From the point of view of the co-evolution of animals and microbiota, animals have probably evolved their molecular hunger and satiety pathways as an adaptation to bacterial chemical signals. In other words, the microbiota really controls our appetite.
With many doubts still to be resolved regarding the functional mechanisms of how this communication occurs, everything seems to indicate that it is the bacterial energy needs that will determine when to eat and what to eat in humans. The closer we stay to the basic needs of human beings and the further away we are from an environment that harms bacterial diversity, the more regulation we will have in our eating behavior and in our habits.