- The Gut-Microbiota-Brain Axis
- Microbes Have Food Preferences, Too
- Microbial Neuroactives
- Microbes Produce Neurotransmitters and Influence Neuroplasticity
- Microbes Shape Host Stress Response, Mood, and Behavior
- Microbial Diversity May Determine How Susceptible You Are to Suggestions from Your Microbes
- Can Manipulating the Gut Microbiota Reduce Cravings?
A whopping 97 percent of women and 68 percent of men report experiencing cravings for certain foods (1). Cravings are thought to be a combination of social, cultural, psychological, and physiological factors and are a major barrier to weight loss and optimal health for many individuals (2).
A recent body of evidence suggests that gut microbes might play a significant role in influencing cravings. Given that microbes co-evolved with us and constantly depend on the incoming dietary substrates that we provide for their own sustenance, it’s really no surprise that they are able to preferentially shape our eating preferences to improve their own chances of survival. In this article, I’ll discuss our current understanding of how microbes shape eating behavior and how you might use this information to combat cravings.
The Gut-Microbiota-Brain Axis
Most of us are well aware of the billions of neurons that make up the fatty, three-pound organ in our skull. But did you know that your gut also contains a dense network of neurons? This network, called the enteric nervous system, governs the physiological function of the gastrointestinal tract. In fact, this network is so robust that it is commonly referred to as the “second brain.”
There are two ways in which they are connected. The first is the circulatory system. We have known for many years that hundreds of different hormonal, neuronal, and inflammation-related signals are constantly relayed between the gut and the brain via the bloodstream (3). Only recently, with the discovery of lymphatic vessels in the brain (4), have we come to understand that these gut-derived signals can likely enter the brain directly from the lymph as well.
The enteric nervous system is also connected directly to the brainstem via the vagus nerve. The vagus nerve acts as a superhighway for communication between the gut and the brain and is the longest nerve cell in the autonomic (unconsciously controlled) nervous system. Studies on the vagus nerve found that vagal blockade can lead to marked weight loss (5), while vagal stimulation triggers excessive eating in rats (6). In the next few sections, I’ll discuss the many other ways that microbes can influence eating behavior.
Craving a certain food? It could be your gut microbes are to blame.
Microbes Have Food Preferences, Too
Different microbes prefer different dietary substrates. While many microbes are “generalists” and can grow on a variety of substrates, they typically prefer one substrate over another, based on the amount of energy they can conserve during the process of breaking it down. Individual genera of bacteria have been shown to have these preferences. For example, Bacteroidetes has been shown to have a preference for particular fats; Prevotella grows best on a carbohydrate source; Bifidobacteria are able to outcompete others in the presence of dietary fiber (7, 8). Other microbes are “specialists” and can only grow on a single nutrient source. Some microbes, such as Akkermansia muciniphila, do not depend on dietary substrates at all and instead thrive on the carbohydrate of the mucus layer secreted by host gut epithelial cells (9).
All of these microbes require a steady stream of substrates to grow and reproduce. Studies have shown that a low concentration of nutrients triggers increased virulence in many microbes as a survival mechanism. Virulence is the ability of a particular microbe to cause damage to the host. For many human-associated microbes, the production of virulence toxins is altered by the detection of simple sugars and other nutrients (10, 11).
When microbes break down (metabolize) dietary substrates, they produce by-products called metabolites. Microbial metabolites include many neuroactive agents (12, 13) that are small enough to penetrate the selectively permeable blood-brain barrier. Studies on chocolate cravings have found that even when eating identical diets, people who are “chocolate desiring” have different microbial breakdown products in their urine than people who are “chocolate indifferent” (14, 15).
So what are some of these metabolites? Short-chain fatty acids (SCFAs), breakdown products produced from the fermentation of dietary fiber in the GI tract, are able to modify the expression of genes in cells throughout the body, including brain cells. In particular, the SCFA butyrate has been shown to dampen the inflammatory response of microglia, the immune cells of the brain (16), and has profound effects on behavior and mood in mice (17).
Other microbially derived molecules are able to mimic hunger or satiety hormones. Your body normally secretes hormones like ghrelin (to stimulate your appetite) and peptide YY (to signal that you are full). Many gut bacteria are able to manufacture small peptides that mimic these hormones.
Interestingly, humans produce antibodies against these microbial hormone mimics in an effort to maintain the integrity of host signaling mechanisms. These antibodies, however, while meant to target microbial hormones, can also bind to mammalian hormones, effectively making them “auto-antibodies” (antibodies that react against one’s own body) (18). Microbes therefore can interfere with human appetite by either directly mimicking satiety and hunger hormones or indirectly inducing this autoimmune response.
Microbes Produce Neurotransmitters and Influence Neuroplasticity
Microbes may not have a nervous system, but they do produce neurotransmitters! More than 50 percent of your body’s dopamine and 90 percent of your body’s serotonin are produced in your gut, along with about 30 other neurotransmitters (19, 20). These molecules are critical for signaling between cells of the nervous system. Dopamine in the striatum and serotonin in the hypothalamus have both been shown to be involved in the regulation of eating behavior (21).
Microbes may also influence neuroplasticity, the ability of the brain to reorganize and create new neural pathways. This is particularly important since the formation of new connections between neurons may be necessary to reshape emotional eating behavior (22). One potent stimulator of neuroplasticity is brain-derived neurotrophic factor (BDNF). Studies have shown that mice lacking a gut microbiota (germ-free mice) have decreased levels of BDNF in the hippocampus, the learning and memory center of the brain. Hippocampal BDNF is also decreased in normal mice following antibiotic administration (23).
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Microbes Shape Host Stress Response, Mood, and Behavior
Poor mental health has long been associated with an increased likelihood to eat unhealthy foods (26). In 2004, a seminal experiment showed that germ-free mice raised in sterile conditions with no gut microbes had an exaggerated hypothalamic–pituitary–adrenal (HPA) axis response to stress (27). The effect was reversed by colonization with a single Bifidobacterium species. A similar 2013 study showed that germ-free mice had increased anxiety-like behavior, which was ameliorated by short-term colonization in adulthood.
Furthermore, a study published in 2012 found that germ-free mice prefer sweets and have a greater number of sweet taste receptors (28). While germ-free mice can tell us a lot about the role of microbes in mammalian physiology, they are certainly not very translatable to our own lives. At the end of this article, I’ll discuss a few human studies that have shown improvements in mood through interventions that manipulate the gut microbiota.
Microbial Diversity May Determine How Susceptible You Are to Suggestions from Your Microbes
Microbial diversity may determine how easily host behavior can be manipulated. Members of the microbiota constantly compete with one another over habitat and nutrients. A less diverse microbial population has fewer distinct microbial species and therefore likely has a few species with large population sizes. Researchers have hypothesized that species with large population sizes are able to use fewer resources for outcompeting other microbial species, leaving more resources available for manipulating the behavior of the host (29).
Interestingly, obese individuals tend to have lower microbial diversity than individuals of a healthy weight (30, 31). This may partially explain why people who are overweight tend to have more difficulty with food cravings. In other words, microbes could be a major barrier to weight loss.
Can Manipulating the Gut Microbiota Reduce Cravings?
In this article, we discussed the connection between gut microbes and food cravings. Research on the oral microbiota may yet provide more links between microbes and our eating behavior. Functional and structural brain imaging alongside microbiota and metabolite analysis will be essential to improving our understanding of the microbiota–brain connection and its impact on human health and disease (32).
If you’re feeling powerless to the will of your microbes right about now, you should know that there are quite a few ways that we can manipulate them! The following list will help cultivate a healthy microbiota and may help you make better food choices.
Several strains of Bifidobacterium and Lactobacillus have been shown to improve anxiety- and depression-like behavior, which tend to alter eating behavior. In a randomized trial, women who ate a fermented milk product containing probiotics showed reduced activity in the insula and somatosensory cortices (emotional reactivity centers of the brain) in response to an emotional recognition task (33).
Prebiotics are foods that selectively feed certain beneficial microbes over others. Prebiotics have been shown to increase BDNF (34), reduce waking cortisol and alter emotional processing (35), and induce satiety hormones (36). Try fermentable fiber in the form of foods like plantains, onions, garlic, and sweet potatoes, or consider supplementing with inulin or resistant starch.
Focus on Nutrient Density
A diverse microbiota tends to be a healthy microbiota. A diversified, nutrient-dense diet provides substrates to a wide range of microbes that can support your health and prevent any one population from gaining too much ground. Many people find that their cravings subside substantially after adopting a nutrient-dense diet for several months. This is likely mediated by a shift in their gut and oral microbiota.
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