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Is it possible to treat mental health disorders by altering bacteria in the gut?
What is the Gut-Brain Axis?
Can the drugs we use to treat psychiatric disorders make patients worse by altering the bacteria living in the gut?
There have been many articles and studies published recently discussing the possible connection between the microflora of the gut and the progression of neuropsychiatric disorders. The bacteria in the gut are affected by many factors, including age, diet, exercise, health, and genetics. Medications can also alter gut bacteria. This post will explore the possible effects of the gut microbiome on various psychiatric disorders.
The Gut-Brain Axis
The Gut-Brain Axis is a network of nerves, hormones, and immunological factors connecting the central nervous system (CNS) to the Gastrointestinal (GI) tract. It appears that the gut flora are involved in this system. An imbalance in the function and composition of these intestinal bacteria is associated with many disease states. 1
The microbes in the gut contain genes that perform metabolic functions. The metabolites resulting from these reactions can produce local effects in the GI environment or gut wall. These microbial metabolites may also be absorbed into the systemic circulation and exert their effects on other organs, including the brain.
It is now known that there is bidirectional communication between the gut and the brain. This communication network is known as the gut-brain axis. 2
Altered microflora of the gut has been associated with depression, other mood disorders, and neurodegenerative diseases. 3
It is known that patients with GI diseases often suffer from mental health issues. 6
We also know that approximately one-third of patients with irritable bowel syndrome (IBS) have depression. 10
In patients with functional gastrointestinal disorders (FGIDs), 36.5% have comorbid psychiatric disorders. The most common of these are general anxiety disorder and panic. 11
Effects of Medications on Gut Bacteria
Psychiatric medications are known to disrupt the microbiome of the gut. 12
Second-generation antipsychotics, such as olanzapine, change the balance of intestinal bacteria leading to obesity.
Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) may inhibit Staphylococcus and Enterococcus growth. 13
The Belgian Flemish Gut Flora Project found both benzodiazepines and antidepressants affected microbiology. 16
The classes of non-antibiotic drugs that have the highest antimicrobial activity are antidepressants, antipsychotics, and benzodiazepines. 17
The drugs we use to treat these psychiatric disorders may be making the conditions worse by altering the composition of the gut flora.
It may be possible to treat psychiatric disorders with living microorganisms. The goal would be to re-establish the healthy flora in the gut resulting in an improved gut-brain axis relationship. This is a difficult subject to study because once ingested; the living organisms are subjected to many negative environmental factors, including digestive enzymes, competitive microorganisms, and pH changes. Despite this difficulty, studies have been done, resulting in positive outcomes.
Gut-Brain Axis and Autism Spectrum Disorders
Autism spectrum disorders are developmental disorders that affect communication and behavior. This is known as a spectrum disorder because there is a wide variety of symptoms involved. Patients with autism have a difficult time communicating, may not respond to their name, and often do not find enjoyment in activities others enjoy. They may also display repetitive, stereotyped behaviors.
The exact cause of autism is not known, but children with ASD often suffer from GI symptoms that correlate with the severity of their disorder. Several studies have reported altered gut bacteria in patients with autism.
A treatment protocol using a fecal transplant was administered to 18 children with ASD (ages 7–16 years). The protocol started with two weeks of antibiotics, followed by a bowel cleanse. The children were then given an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily maintenance doses for 7-8 weeks.
At the end of treatment, there was an 80% reduction of GI symptoms, as measured by the Gastrointestinal Symptom Rating Scale. This included a significant decrease in abdominal pain, indigestion, diarrhea, and constipation. These improvements were still evident eight weeks after treatment. The behavioral symptoms also improved significantly and also remained eight weeks post-treatment. This procedure seemed to be effective for both ASD symptoms as well as GI symptoms and continued long after treatment was completed. 21
Gut-Brain Axis and Bipolar Disorder
One study showed that patients with bipolar mania were twice as likely to have taken a recent course of antibiotics. 22
It has been suggested that treating bipolar patients with probiotics could help reduce hospitalizations. A small study found treating acutely manic patients with probiotics led to a decrease in the readmission rate. Dr. Faith Dickerson randomized 66 patients to receive a probiotic capsule or placebo for six months after hospitalization for mania. The probiotic, or placebo, were given in addition to the regular medication regimens. Of these 66 patients, 24 or 73% required rehospitalization, while only eight (24%) of the probiotic group was hospitalized. The probiotic patients who were admitted also had a shorter hospital stay than those treated with a placebo.
The probiotics used in this study were Bifidobacterium lactis (bb-12), and Lactobacillus rhamnosus (LGG). These strains are also found in breast milk. 23
Gut-Brain Axis and Major Depressive Disorder (MDD)
It has been shown that mice raised in a sterile environment (germ-free mice) have an exaggerated response to stress. This can be reversed by inoculating these mice with feces in their early development. 24
This suggests that gut microbial stimulation helps to shape healthy brain development during the early stages of life. 25
A review published in 2017 in the Annals of General Psychiatry concluded that treatment with probiotics might improve MDD symptoms. The mechanism is likely a combination of serotonin availability as well as decreased inflammation. More comprehensive studies need to be completed to determine the utility of such a treatment in depression. At the present time, there is likely no harm in supplementing antidepressant medications with probiotics. 26
Psychobiotics are substances that alter the bacteria of the gut. These may be live bacteria (probiotics) or prebiotics. Prebiotics are compounds that change bacterial composition or activity when fermented in the digestive tract. 27
In a study of 55 healthy volunteers, subjects received either fermented milk containing Lactobacillus casei Shirota, or a placebo for three weeks. The study subjects falling into the bottom third of mood scores showed significant improvement as compared to the placebo group. There were no overall changes in mood in this study, which may suggest Lactobacillus has a ceiling effect. In other words, people who are already relatively happy may not have an increase in mood after ingesting the probiotic. 28
It is important to note that not all studies have shown benefits regarding probiotics. A recent review found little evidence of positive outcomes from these substances. 29
The Gut-Brain Axis is a fascinating topic that deserves much more research. I believe we can all benefit from eating a healthy diet, exercise, and possibly probiotic supplementation.
The evidence suggests that gut bacteria are vital in helping to develop the brain at a very early stage of human development. It is also evident that many of the medications we use to treat mood disorders such as depression, anxiety, and bipolar disorder, have an effect on the microbiome of the gut.
In the future, we may be able to either successfully treat these disorders with specific bacterial agents, or supplement the healthy flora destroyed by the medications we employ to treat these maladies.
I do know that I benefitted from eating a whole food diet during my Whole30 experience. My mood improved; I slept better and was more alert and happier in general. I can’t be sure this has anything to do with the microbiome in my gut, but it is certainly possible. I hope you have learned something from this post. If you have any questions, please feel free to reach out to me.
In the next post, I plan to write about happiness. This is something I have been looking forward to. I want to share my secrets for staying happy and improving your mood. I think you will all enjoy it.
Have a great day, and stay healthy!
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Michael J. Brown, RPh, BCPS, BCPP
Mr. Brown is a Clinical Pharmacist specializing in pharmacotherapy and psychiatry.
Feel free to send Michael a message using this link.