Dysbiosis and Despair

Part 2 Mood Disorders

How many times have you said, ‘I feel like shit today’? You may have been onto something. According to the latest science, the poop that’s spackled to the walls of your intestines can alter your feelings. Not exactly, the poop itself. More accurately the intestinal microbiome may contribute to mood disorders (and the psychological abnormalities that lead to mood disorders).

Mood disorders are a category of mental illnesses characterized by significant and persistent disruptions in a person’s emotional state, impacting their mood, behavior, and overall well-being. These disorders can manifest as prolonged periods of sadness, irritability, or hopelessness (depression), or as periods of elevated mood, energy, and activity (mania or hypomania), or both.

The intestinal microbiome is the foundation of the Gut-Brain Axis: The gut microbiota influences brain function through bidirectional communication via neural (vagus nerve), immune (cytokines), and metabolic (short-chain fatty acids (SCFAs), tryptophan metabolites, GABA, serotonin, and dopamine) pathways. Microbiota alterations may impair hypothalamic-pituitary-adrenal axis regulation (which, in turn, affects both psychological stress level (cortisol) and hormonal balance throughout your body). What’s more, microbial metabolites (e.g., SCFAs ) and inflammation play roles in psychiatric symptoms.

When the intestinal microbiome gets out of whack, it’s called dysbiosis. Dysbiosis (imbalanced microbiota) is linked to mood disorders. Dysbiosis may contribute to neuroinflammation, altered neurotransmitter production (which can affect brain signaling), and impaired brain connectivity. Dysbiosis (imbalanced microbiome) can increase gut permeability (leaky gut), allowing inflammatory molecules to enter the bloodstream, disrupt blood-brain barrier integrity and affect the brain.

Now that you’ve got the basics, let’s get down to the nitty gritty.

In 2019, Chinese researchers evaluated ninety people, thirty with bipolar disorder (BD), thirty with depression (major depressive disorder, MDD) and thirty controls (no mood disorder). Compared to healthy controls, both patient groups had altered gut microbiota, including reduced microbial diversity (shoutout to DEI for a healthy gut-brain axis). Specifically, certain bacteria (e.g., Bacteroides and Prevotella) were less abundant in those with mood disorders, while others (e.g., Clostridium and Streptococcus) were more abundant.

In 2020, Swiss researchers published a review article which explored the relationship between gut microbiota and the development and progression of MDD and BD, emphasizing the gut-brain axis as a key mechanism.

The studies the Swiss scientists reviewed showed reduced microbial diversity in MDD patients, with lower abundance of beneficial bacteria (Bifidobacterium, Lactobacillus) and increased pro-inflammatory species. They determined that altered microbial metabolites, like reduced butyrate, may contribute to depressive symptoms via inflammation and impaired neuroplasticity (the ability of the brain to rewire itself).

Similar dysbiosis patterns are observed in BD, particularly during depressive episodes, with shifts in microbial composition (increased Clostridium). Manic episodes show distinct microbial profiles, suggesting state-specific alterations.

In 2022, researchers in the Netherlands reviewed the role of the gut microbiome in three major psychiatric disorders: major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). For more on schizophrenia see https://brain2mind.substack.com/p/dysbiosis-and-psychosis

The studies the Nordic scientists evaluated show dysbiosis (imbalanced gut microbiota) in MDD, BD, and SCZ, with reduced microbial diversity and specific bacterial changes compared to healthy controls. For example, lower levels of anti-inflammatory bacteria like Faecalibacterium are common in these disorders.

OK, now what can you do about it?

There’s increasing evidence that probiotics, prebiotics, and fecal microbiota transplantation may all play a role in alleviating mood disorder.

Probiotics—live microorganisms conferring health benefits—can modulate gut microbiota composition and function, potentially influencing brain activity and behavior.

Prebiotics like inulin may promote SCFA-producing bacteria, potentially stabilizing mood. Prebiotics like galactooligosaccharides (GOS) may enhance beneficial bacteria and reduce inflammation. Prebiotics like fructooligosaccharides (FOS) may support beneficial bacteria and reduce stress responses.

Diet (e.g., Mediterranean diet) also influences microbiota and mood outcomes. Diets rich in fiber, omega-3s, and fermented foods (e.g., yogurt, kefir) have been associated with reduced anxiety and lower depression risk.

Poop transplant from healthy donors to depressed patients is under investigation, with early trials showing symptom improvement in some cases. For more on poop transplant see https://brain2mind.substack.com/p/dysbiosis-and-psychosis

That probiotic stuff sounds interesting. Where’s the proof?

Glad you asked.

In 2018, doctors at the prestigious Johns Hopkins investigated whether probiotics could prevent rehospitalization in patients with BD. It was the highest level of evidence: a randomized, double-blind, placebo-controlled trial. The study involved 66 patients hospitalized for acute mania.

Hospitalized patients received either a probiotic supplement (containing Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) or placebo alongside standard treatment for 24 weeks post-discharge. The probiotic group had a significantly lower rehospitalization rate compared to the placebo group. Even in those who were sent back to the psych ward, probiotic treatment delayed time to rehospitalization.

Probiotics are also likely to improve MDD. In 2020, a review by Irish scientists highlighted animal studies, which demonstrated that specific probiotic strains (e.g., Lactobacillus and Bifidobacterium species) can reduce anxiety-like behaviors, improve stress responses, and enhance cognitive function. Human clinical trials, though limited, suggest probiotics may alleviate depressive symptoms, reduce anxiety, and improve mood.

In 2017, Canadian scientists explored the effects of a probiotic containing Bifidobacterium longum on depression, anxiety, and brain activity in patients who also suffered from irritable bowel syndrome (IBS). The study involved 44 IBS patients with mild-to-moderate anxiety or depression.

Participants received either probiotic or placebo daily for 6 weeks. The probiotic group showed significant reduction in depression scores compared to placebo, but no significant change in anxiety scores. IBS symptoms improved in both groups, with no significant difference. Functional MRI revealed reduced activity in limbic regions (e.g., amygdala) and improved connectivity in areas linked to emotional regulation in the probiotic group.

Then, there’s the Chicken and the Egg Quandary

Mental illnesses can alter the microbiome (e.g., via stress or poor diet), and dysbiosis can worsen symptoms, creating a feedback loop. Psychiatric drugs like antipsychotics (e.g., risperidone) and antidepressants (e.g., SSRIs) can alter the microbiome, potentially influencing treatment outcomes.

I hope you’ve learned something about how the bugs in your gut can affect your mental health. But there’s much more… The microbiome may also affect Alzheimer’s Disease. If you’d like to learn about that, check out: https://brain2mind.substack.com/p/having-the-wrong-bugs-in-your-belly