Key concepts covered in this article: Depression in the gut DOES exist- and is very similar with the depression in the brain. Both are more common in MS and other chronic conditions. There are many similarities between “depression” in the gut and the classic depression.
1.The Classic Depression (In The Brain). Medical Theories of Depression
2. Meet Your Second Brain : The Gut
3. Depression In The Gut DOES Exist- And Is Very Similar With The Depression In The Brain
4. Some Drugs/ Therapies Help Manage Both- The Depressed Brain And The Depressed Gut
1.The Classic Depression (In The Brain). Medical Theories of Depression
Everyone knows about the classic depression and its symptoms: sadness, feelings of guilt and worthlessness, slow thinking and decreased ability to concentrate, sleeping problems, changes in appetite and fatigue.
What causes depression ? A few theories explaining what causes depression:
Depression is caused by an imbalance in brain neurotransmitters- particularly deficiencies in serotonin, dopamine, norepinephrine. More recently, several other neurotransmitters had been found out of balance in depression- including a shortage of GABA and excess histamine and glutamate. Standard treatments still rely on this old theory, and therefore therapy involves the well-known antidepressants that that aim to improve the levels of these neurotransmitters, as well as anti-anxiety drugs. A quick note on histamine: mast cell activation/histamine intolerance had been linked with depression.
Depression in an inflammatory disease, and has an autoimmune component. It is driven by low grade inflammation. This concept also makes sense considering that depression correlates with increased levels of proinflammatory molecules like TNF-α and IL-6 and activation of the stress hormones/HPA axis [1],[2].Seeing depression as an autoimmune disease may seem a bit weird at first. But if we think that the brain has more immune cells than neurons, would make sense to see these immune cellsinvolved in depression. Technical:In the brain, the number of glial cells is 10-15 times greater than that of neurons. Astrocytes, oligodendrocytes (oligodendrocytes in the CNS and Schwann cells in the PNS), and microglia.Microglial cells are immune cells and follow the actions and functions of that immune system. Astrocytes play a key role in neurotransmission and in neuron metabolism. Oligodendrocytes in the brain (Schwann cell in the periphery) produce myelin. Depression correlates with Th1/Th2 imbalance.
Depression is caused by an imbalance in sugar metabolism. This concept had been researched since scientists observed a close relationship between depression and diabetes. There is now evidence that insulin resistance (including insulin resistance in the brain) plays a key role in depression because insulin regulates neuron signaling and plasticity [3].
The BDNF theory of depression. BDNF is a protein known as a “brain fertilizer” because plays a key role in the formation of new neurons, protection of the healthy ones, repair the damaged ones and improve neuroplasticity (the connection between brain cells). According to this theory, a loss of BDNF is directly involved in the development of depression.
Altered gut flora (medically known as dysbiosis) is associated with depression, as the gut and the brain are connected via vagus nerve (gut-brain axis) [4].
There is scientific evidence for all these theories. I see them all connected. The neurotransmitter deficiency can be due to inflammation and immune system imbalance. The underlying cause of inflammation and autoimmunity can be a result of the insulin resistance. Low BDNF can be due to inflammation or insulin resistance. BDNF and serotonin work together and one influences the other [5]. BDNF is produced and secreted by microglial cells in the brain. Yes, they are all connected.
2. Meet Your Second Brain : The Gut
More and more evidence confirms that the gut truly is your second brain. To be more specific, the enteric nervous system (ENS) in the gut has roughly the same amount of nerve cells as your spinal cord. Just like your brain, the gut sends and receives nerve impulses. That “gut feeling” is not just an expression- the gut does perceive and respond to emotions.
The same neurotransmitters found in the brain are also made in the gut and play important roles in gut motility and the overall gut health and digestion -for example, more than 90% of serotonin is made in the gut. Just like the brain, the gut is also rich in immune cells. In fact 80% of the immune system is in the gut.
The brain and gut are connected via vagus nerve, forming the gut brain axis. Contrary to the popular belief, the gut seems to be in charge to tell the brain what to do (and less the other way around). An estimated 90 % of the nerve fibers that connect the gut to the brain carry information from the gut to the brain and only 10% of the nerve fibers will bring information from the brain to the gut. While the gut communicates with the brain, it can also work independently (ENS being part of the autonomic nervous system).
3. Depression In The Gut DOES Exist- And Is Very Similar With The Depression In The Brain
I wrote about chronic constipation, SIBO-C and IBS-C in my previous article, where I suggested that all 3 could be only one disease and they have the same cause -the overgrowth of methane producing microbes.
What is chronic constipation? What about SIBO-C or IBS-C? They are basically “depression” in the gut- or at least this is how I call them. That’s because the same changes that occur in the depressed brain also develop in the “depressed” gut and all theories of depression development also apply to the digestive tract (when is “depressed”). Both forms of depression respond to the same treatments, too. Let’s look at the details.
The neurotransmitter theory of depression. This time, in the gut: most studies correlate chronic constipation/IBS/ SIBO-C with serotonin deficiency. However, just like in depression, other neurotransmitters will also be imbalanced (ie dopamine, GABA and norepinephrine, histamine, glutamate). Mast cell activation had been linked with IBS. [6], [7].
The inflammation/autoimmune theory of depression. This concept is well-known in gastrointestinal conditions. Inflammation and autoimmunity are well-established in inflammatory bowel diseases (Crohn’s and ulcerative colitis). There is also evidence of the low grade inflammation and autoimmunity in chronic constipation, IBS-C and SIBO-C — more details in this article, plus [8].
The sugar metabolism imbalance theory of depression. Altered sugar metabolism (both hypo and hyperglycemia) correlates with constipation (or what I called, the “depressed” gut) [9]. IBS and SIBO are known to be more common in people with diabetes/metabolic syndrome [10],[11] and the carbohydrate rich foods (FODMAPs) are improperly digested in these cases. Altered gut microbiome correlates with sugar imbalances as well [12].
The BDNF theory of depression — is also seen in the “depressed” gut. BDNF plays a critical role in gut motility and lower BDNF expression had been documented in chronic constipation. Technical: BDNF plays a key regulatory role in gut motility in slow colonic transit constipation. It was mediated by altering the intestinal innervation structure, as well as smooth muscle secondary degeneration through a mechanism involving TrkB-PLC/IP3 pathway activation [13]. On the other hand, higher BDNF levels had been found in diarrhea predominant IBS, and this increase also seem to correlate with abdominal pain/hypersensitivity [14].
The dysbiosis theory of depression is obvious in the “depressed “ gut. Dysbiosis is a key problem in all -chronic constipation, SIBO-C and IBS-C. The link between gut and brain also explains why these conditions correlate with increased risk of depression and anxiety [15],[16].
4. Some Drugs/ Therapies Help Manage Both- The Depressed Brain And The Depressed Gut
Depression is treated with antidepressants, anti-anxiety drugs, psychotherapy, hypnotherapy. Probiotics had also been researched and had been found helpful to relieve depression [17].
Not a coincidence: the “depressed “ gut responds to the very same drugs. Antidepressants and anti-anxiety drugs had been found to ameliorate symptoms of constipation, IBS-C and SIBO-C (key mechanism: serotonin promotes intestinal motility, while GABA helps decrease pain) [18]. Psychotherapy and gut directed hypnotherapy had been found beneficial [19],[20]. A number of probiotic strains are known to help manage constipation, SIBO-C and IBS-C.
Of course, I support the use of natural therapies, particularly the ones that had been researched and found to be effective. While antidepressants and anti-anxiety drugs work sometimes, they have many side effects (including significant, negative changes in the gut microbiome). I wrote here and here about alternatives to antidepressants and anti-anxiety drugs.
The more we learn about the gut microbiome, the more we realized that the gut health is crucial to the overall health. Maybe gastroenterologists, neurologists and psychiatrists will work together in the future to address both forms of depression. Both depressions are more common in MS and should be treated-if you want to reverse MS.
