As seen in Psychology Today.
Psychiatry has undergone several major evolutions over the last century. We’ve gone from a primarily psychoanalytic approach centered on talk therapies to a more neurobiological approach that pairs psychotherapies with medications capable of targeting specific neurotransmitters in the brain. Both modalities, psychotherapy and psychopharmacology, rose to prominence rapidly and disrupted the intellectual equilibrium that had existed beforehand.
I believe that we are in the midst of another period of disruption.
As we approach the middle of the 2020s, it is clear new treatment modalities are emerging that take advantage of new insights into the communication networks between the central nervous system (CNS) and the rest of the body. As research has revealed, the extent of the communication between these networks reveals that the brain’s position within the body’s immune system is certainly privileged, but hardly inviolate. Moreover, these insights strongly suggest that the pathophysiology of many mental illnesses starts with dysfunctions in other parts of the body, particularly the gut.
Understanding these mechanisms will allow psychiatrists to better treat patients.
The Gut Microbiota and the Brain
The gastrointestinal [GI] tract contains around 100 million nerve cells that run from the esophagus to the anus. Additionally, some 5 million distinct genes and tens of trillions of organisms reside within the GI tract (primarily in the large intestine), and include at least 2,000 species of bacteria, archaea, fungi, protozoa, and viruses. This universe of microorganisms makes up the gut microbiota.
The gut microbiota is quickly populated after birth and more than 60% of a neonate’s microbiome comes directly from their mother’s microbiome. The makeup of microbes that ultimately call an individual’s gut home is also influenced by genetics and environmental factors that include diet, internal pH, and presence and concentration of specific digestive enzymes. Moreover, one’s gut microbiota is not set in stone; specific microbial populations ebb and flow throughout an individual’s life.
Despite this state of constant flux and evolution, the primary functions of the gut microbiota remain constant. Some of these responsibilities include protecting us from pathogens, assisting with nutrient and mineral absorption, and contributing certain enzymes not encoded within the human genome that allow for the synthesis of vitamins and the metabolism of polysaccharides and polyphenols. It also plays a role in the synthesis of neurotransmitters, which ultimately make their way up to the CNS via several bidirectional signaling pathways collectively known as the gut-brain axis. There is even evidence that the dopamine that rewards rigorous exercise (i.e., “runner’s high”) is produced in the gut and sent to the brain via the peripheral endocannabinoid system. According to a study published at the end of 2022 in Nature, when this line of communication is disrupted with antibiotics, the mice are deprived of that dopamine boost and they lose the motivation to continue exercising.
While human motivations are typically different from the motivations of lab mice (especially when it comes to exercise), this finding does offer a partial explanation for disparities in exercise capacity among people. More importantly, it suggests that major changes to the gut microbiota can lead to disruptions in communication along the gut-brain axis, thereby influencing behavior in ways we might not notice. Studies involving fecal transplants of depressed individuals to otherwise healthy mice, who then begin to show symptoms akin to depression and anxiety, as well as changes to their metabolism of tryptophan, suggest that alterations to the gut can impact mood, as well.
Gut Dysbiosis and Inflammation
There has recently been a flood of evidence suggesting that a significant amount of the crosstalk between the CNS and gut is also mediated through the immune system. Consequently, problems in the gut may be responsible not only for inflammatory GI disorders such as ulcerative colitis and irritable bowel syndrome, but also instrumental in the development of immune dysfunction that then contributes to at least some neurodevelopmental and psychiatric disorders.
Unfortunately, there is not a single microbial culprit that is causing all these problems, which means there isn’t one species that can be targeted. Moreover, microbial profiles vary from gut to gut and have a great deal of plasticity, so any notion that there is one ideal profile is simply not accurate. Instead, researchers have realized that disorders arise as a result of dysbiosis, which is when the microbial populations in an individual’s gut become unbalanced. This imbalance can happen because of a serious loss of overall microbial diversity, an overgrowth of problematic bacteria, the disappearance of good bacteria, or any combination of the three.
During dysbiosis, there are multiple mechanisms that can contribute to neuropsychiatric disorders, including through vagal pathways, the endocannabinoid system (as noted above), or the immune system. The latter pathway operates through inflammation, which can alter the permeability of the blood-brain barrier and allow inflammatory proteins to enter into the CNS, disrupt homeostasis, and contribute to neuroinflammation. Neuroinflammation then causes structural damage within the CNS and that process appears to correlate with psychiatric symptoms, particularly depression.
In other words, problems that start in the gut may ultimately lead to problems that were once believed to be within the insular world of the psyche.
What Can We Do?
Within the last decade, researchers have clearly charted these pathways and slowly elucidated the connections linking the gut, the immune system, and the brain. They have repeatedly found that an unhealthy diet, lack of sleep, and lack of exercise contributes to dysbiosis inflammation, metabolic disorders, and neuropsychiatric conditions. Conversely, a healthy diet, adequate sleep, and exercise can play a preventative role with respect to these maladies.
Though not particularly new or exciting, the definition of “healthy diet” has remained consistent and consists of micronutrient-dense and high-fiber foods (which may or may not include animal proteins) that promote a diverse gut biome. Simply put avoid simple sugars, refined flours, and heavily processed foods that are high in saturated and trans-fats. If we want to promote better mental health for our patients based on the most cutting-edge research, encouraging these kinds of dietary changes is an excellent place to start.