Gut Health… From Antidepressants?

Gut Health… From Antidepressants?
Scott Resnick MD 2022

We all know that gut health is associated with mental health. Or at least we should all know this. With the extensive amount of research supporting this, it is my belief that one is remiss to be addressing mental health issues without considering the impact of the gut.

More and more, research shows that the communications between the bacterial species in our gut and the workings of our brain are bidirectional. Not only do the bacterial communities in the gut influence the workings of our brain—likely through the vagus nerve— but our brain similarly has the capacity to influence the bacteria within our gut.

How We Think Antidepressants Work

Let’s take a step back for a moment. The practice of psychiatry, and the multiple antidepressants prescribed by our primary care doctors, are known to influence neurotransmitter activity at the nerve synapses.  SSRIs and SNRIs are selective serotonin (S) and Norepinephrine (N) Reuptake Inhibitors. It is believed that these medications alter neurohormone balances within our brain, thus “treating” depression.

(You’ll notice I’ve emphasized the word treating in the previous paragraph. Many of the studies that have followed medication use for depression only go out for 3-6 months. These studies generally only show a 50% improvement in depression, while some 40% of patients experienced significant side effects, notably fogginess, weight gain and loss of sexual functioning.)

And what about the brain? Is it possible that these medications are influencing our moods outside of our central nervous system? In this post I will explore the possibility that these medications aren’t operating only centrally, but with the serotonin system in the gut as well.

What? Is this medical blasphemy? Any conventionally trained physician knows that these medications influence the brain! At least that’s what we were taught in medicals school.

New Perspectives on Depression:  A Healthy Gut

As with so many things in medicine these days, the paradigm is changing. A 2021 paper published in the reputable journal Frontiers in Psychiatry, asks us to reconsider this perspective1.

Here, the authors state:

“(We) propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted.”

This proposal is based on the fact that 90% of our body’s serotonin is produced in the gut and that these SSRIs influence gut-based neurons, Additionally, this class of medications has antimicrobial properties that can directly alter the microbiome balance.

But the contributing mechanisms extend even further. Extensive data associate neuroinflammation with depression, stress, and the cognitive decline seen in conditions such as Alzheimer’s Disease.

Researchers are showing that the SSRI class of medications directly affects peripheral inflammatory cytokines. These potent little molecules are damaging to the brain. In simpler terms, antidepressants may influence both the gut bacteria, as well as the inflammatory molecules produced by our immune system.

Now let’s expand our view even a little farther. Out gut contains some 100 trillion bacterial cells, some of which themselves may have intrinsic disease-causing properties. But the number (and volume) of immune-activating molecules found in toxins, foods, and medications greatly outweigh the infrequent presence of a true bacterial infection.

A New Look at Depression and Gut Health

So, let’s summarize with a “new” view on the role of SSRIs and SNRIs in the treatment of mental health.

First, it may be that these medications work directly on the microbiome, the bacteria themselves, to influence mood. Perhaps a future psychiatrist will collaborate one’s gut health with medication choices. This is doable. It will require shared databases, the addition of epigenetic and genetic factors, and some pretty powerful computers.

Next, it may be that the commonly prescribed antidepressants aren’t only influencing the bacteria in the gut, but the numerous serotonin-producing nerve terminals. Here’s another place where we might begin to reframe our thinking about mental health. Perhaps the integrity and function of the gut lining, the mucosa, is an important variable in mental health.

What if our focus was on inflammation, and we primarily addressed the different pathways that produce it? Inflammation is unquestionably the primary human toxin. Treating it requires a more holistic view, incorporating more aspects of biology, biochemistry, and the environment.

What if a Healthy Gut Meant…?

…We were to simply return to basic biochemistry? What if we reminded ourselves that impaired mitochondrial function, immune activation, and disrupted barriers to the outside world all increased inflammation? Would we begin to address these as a component of depression?

What if we remembered that inflammatory cytokines, a byproduct of all of the processes listed above, cross freely into the brain?

What if we began to think in a more encompassing way about mental health, augmenting the current treatment paradigms with modalities like nutrition and stress reduction?

Mental health of the future may use SSRIs independently for inflammation. There will be a time when our clinical interventions focus more on the gut, detoxification and epigenetic factors like stress and diet.

To truly effect significant changes in human health, the medical community will have to assimilate a more diverse thinking process. Approaching mental health from a gut-centric perspective might be a good start.


  1. Serotonin reuptake inhibitors and the Gut Microbiome: Significance of the gut microbiome in relation to mechanism of action, treatment response, and side effects and tachyphylaxis. Sjostedt, P. Front Psychiatry, 2021:12; 682868.

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