As seen in Psychology Today. Featured image from Science Photo Library/Pixels (used with permission).
There has been a surge in interest in the role that gut dysbiosis plays in psychiatric and neurocognitive disorders. Even just a decade ago, the brain was believed to be a highly privileged organ that was largely shut off from the rest of the body due to the existence of the blood brain barrier (BBB) and that communicated with other bodily systems in a top-down manner. Consequently, psychiatry tended to focus exclusively on the central nervous system (CNS) when treating psychiatric conditions. This paradigm is giving way to a new type of thinking that recognizes the vast interconnectivity between the brain and multiple other systems, particularly the gut and the trillions of microorganisms that make up the gut microbiota. Ultimately, this may impact the way we treat patients.
A recent systematic review by Grau-Del Valle and colleagues in Frontiers in Psychology is an excellent starting point and reveals how far research has come in just a few years. A great deal of the information included below is taken from that paper.
What Is the Gut Microbiota?
The gut microbiota is a dynamic ecosystem comprised of bacteria, archaea, fungi, protozoa, and viruses that all reside within our gut, primarily in the colon or large intestine. The composition of each individual’s gut microbiota fluctuates throughout one’s life and is determined by genetics and environmental factors that include diet, lifestyle choices, and even stress levels. Regional differences in microbial compositions have also been observed.
The gut microbiota is one of our first lines of defense against pathogens that enter into the gastrointestinal (GI) tract. Many organisms within our gut also assist with nutrient and mineral absorption by contributing certain enzymes not encoded within the human genome, allowing for the synthesis of vitamins and the metabolism of polysaccharides and polyphenols. The gut microbiota also plays a role in the regulation of the immune system, hormone secretion, and the synthesis of neurotransmitters like dopamine and serotonin.
What Is the Gut-Brain Axis?
In addition to being home to the microbiota, the GI tract also contains around 100 million nerve cells known as the enteric nervous system (ENS). The ENS interacts with the gut microbiota and is also engaged in constant, bidirectional communication with the central nervous system (CNS) via the gut-brain axis (GBA). The vagus nerve is the primary highway of the GBA, along which travels signaling chemicals that include neurotransmitters, cytokines, and hormones. These chemicals can encourage neuronal modulation, immune response, and endocrine activity. Communication via the GBA appears to also influence cognition, behavior, emotion, stress response, and executive functioning during psychotic episodes.
What Is Dysbiosis?
It’s important to understand that research has found some correlation between individual taxa of bacteria and certain disorders but thinking that some bacteria are good while others are bad paints a somewhat inaccurate picture. Certain taxa of bacteria only become “bad” when they proliferate and disrupt the mutually beneficial relationship they have between host (us) and the other microorganisms in our gut (symbiosis). Organisms that are otherwise benign symbionts that can become pathological are known as pathobionts.
Therefore, rather than thinking in terms of good or bad taxa, one should rather think of good and bad within the context of balance or symbiosis. Therefore, the good is promoting symbiosis while discouraging imbalances or disruptions in symbiosis (dysbiosis) and allowing pathobionts the opportunity to run riot.
Gut Dysbiosis and the GBA
Gut dysbiosis affects the GBA by interfering with healthy signaling between the CNS and ENS. For example, several studies have found that the gut microbiota of depressed patients is significantly different from healthy controls and upsets homeostasis. This leads to several pathological changes in the gut. It appears to adversely affect the integrity of the gut epithelium (i.e., “leaky gut”), which heightens inflammatory responses. Peripheral inflammatory signals then cross the BBB via the vagus nerve, causing neuroinflammation and depressive symptoms. Neuroinflammation then activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing cortisol. Excessive cortisol levels promote gut pathology and inflammatory responses, leading to a leaky gut.
It remains unclear if this cycle begins in the gut or the brain. However, it implicates multiple sites of dysfunction within the CNS that are believed to be associated with psychiatric and neurological disorders, and not only depression. As the authors of the review note, “We confirm an association between psychiatric disorders and the gut microbiota composition.”
What Disorders Are Associated with Gut Dysbiosis?
The authors of the review identified ten disorders that could be affected by gut dysbiosis in various ways:
- Anorexia nervosa
- Attention-deficit/hyperactivity disorder (ADHD)
- Autism spectrum disorders
- Binge eating disorder
- Cognitive decline
- Depressive symptoms
- Generalized anxiety disorder
- Post-traumatic stress disorder (PTSD)
- Psychotic episodes/disorders
Is the Gut Microbiota a Potential Target for Treatment?
The efficacy of various treatments remains an open question, but preliminary studies have found that discouraging gut dysbiosis and promoting the growth of specific taxa may help with the management of some psychiatric symptoms. Dietary interventions that include eating higher levels of dietary fibers, plant compounds, vitamins, minerals, and polyunsaturated fatty acids, while reducing one’s consumption of simple sugars, have been shown to reduce inflammation and may improve gut health. Probiotics (including fermented foods and supplements that introduce live microorganisms to the gut) and prebiotics (substrates like fructo-oligosaccharides and galacto-oligosaccharides, as well as plant-based compounds that promote the growth of certain bacteria taxa in the gut) have also been shown to reduce dysbiosis.
A more intensive treatment is a fecal microbiota transplantation (FMT), which is a procedure involving the delivery of a healthy donor stool into the colon of the patient.
Though the authors of the review found “clear dysbiosis of the gut microbiota in all the psychiatric disorders studied,” there is still far more research to do before we can confidently say that psychiatric disorders and symptoms can be treated by targeting the gut microbiota. Still, the research is very exciting and may soon lead to new strategies in the clinical management of multiple disorders.