The Bacteria That Mold Your Brain
Recent research turns to the microbiome to understand (and shape) behavior.
Posted September 28, 2016
Guest post by Daniel Hass
“Tell me what you eat, and I will tell you what you are.”
This phrase, coined by Jean Anthelme Brillat-Savarin in the The Physiology of Taste, was over a century ahead of its time.
The commonly-held aphorism is true in more ways than one. In one respect, it means that the food you eat becomes a part of your person, and this has long been known — amino acids from digested proteins are incorporated into our own proteins, and the energetic sources from our diet (such as sugars or fatty acids) are added to our own stores of energy.
In another respect, the quote can mean that the food you eat influences who or what kind of person you are. This interpretation is also true – the substances you consume can alter your brain chemistry, and thus behavior.
Microorganisms in your diet have a fascinating route by which they can change the brain through our microbiome – the ecosystem of bacteria, archaea, protozoa, fungi, and viruses that live on and interact with our bodies. Each adult has about 1 kg of these microbes, which are highly diverse, containing approximately 100 times as many genes as the human genome.
The diversity and composition of these microbes in the gut is strongly influenced by diet. For example, mice fed a plant based low-fat diet have a microbial profile that is completely altered by exposure to a high-sugar, high-fat ("Western") diet, which increases the proportion of several classes of bacteria, including Erysipelotrichi and Baccili.
How metabolism affects the brain
Microbes participate in metabolism, in part, by producing bile acids to help digest food and by synthesizing choline and short-chain fatty acids (SCFAs). Deficiencies in choline or SCFAs can cause fatty liver disease or even cirrhosis. Additionally, butyrate derived from the microbiome is necessary to regulate energy use in the colon.
Many of the metabolites produced by microbes are also active in the nervous system, and the bacterium Bifidobacteria infantis can even act as an antidepressant through its regulation of kynurenine/tryptophan metabolism, similar to the actions of some antidepressant medications such as elective serotonin reuptake inhibitors (SSRIs), which seek to increase the concentration of synaptic serotonin.
Gut microbes also affect the immune system. The SCFAs produced by gut microbes that are necessary for a healthy liver also regulate the activity of various immune cells, including macrophages and T-cells.
These cells regulate inflammation, and the molecules they secrete directly communicate with cells in the brain. For example, it is well-characterized that the use of cytokines (molecules frequently secreted by immune cells) to treat cancer or hepatitis C can lead to behavioral alterations such as depression.
Direct influences on the brain
The microbiome can also have a more direct influence on brain chemistry by altering neurotransmission in the enteric (gut) nervous system. Because the enteric nervous system communicates with the central nervous system, the activities of microbes can actually regulate levels of the neurotransmitters GABA, norepinephrine, serotonin, and dopamine in the gut. Through the connections between gut and brain, these microbes can alter mood, emotional state, and anxiety.
Mapping behaviors related to the microbiome
The degree to which behaviors are influenced by the microbiome is difficult to map, given the diversity of microbes which can alter human health. This implies that the microbiome can have as diverse and far-reaching consequences to human health as an organ. Some even refer to the microbiome as an "acquired" organ.
However, the full functionality of this organ is unclear. To illuminate the role of microbes in various behaviors and in disease directly, researchers study mice that lack a functional microbiome. These mice, termed "germ-free," or GF, are readily distinguishable from normal mice on the basis of how they behave.
GF mice often display traits associated with autism. For example, GF mice do not prefer interacting with new mice over other novel objects. Other studies have found GF mice to have an exaggerated stress responses, displaying symptoms that indicate anxious and depressive behaviors.
The microbes found in humans with autism or depression also deviate from those without. Microbiome data suggests that in major depressive disorder, patients have more bacteria from the phyla Bacteroidetes and Proteobacteria, and fewer bacteria from the phylum Firmicutes. Microbiome data on autism spectrum disorder patients suggest other disruptions in the microbial community, including higher levels of Clostridia, Desulfovibrio,Sutterella, and Bacteroides, and lower levels of Firmicutes, Prevotella, and Bifidobacter compared to control subjects, suggesting that developmental or psychiatric disorders could either cause or be caused by a disruption in the composition of microbes.
In the long-term, modifying the levels of specific microbes may be considered in a patient's treatment plan. Unfortunately, we are still far away from being able to confidently make such manipulations.
However, the methods of altering microbial composition, such as dietary changes and fecal transplantation, are minimally invasive and may offer a simple approach by which people can improve their health. So don’t underestimate the importance of “thinking with your stomach."
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