Gut And Brain Connected: How The Microbiome May Change Response To Bipolar Treatment

Bipolar disorder is a mood-affecting condition that is still difficult to treat properly. Studies show that medications used for the disorder also change the bacteria in the gut, which can help improve symptoms but can also cause negative effects, such as an increase in bacteria linked to antibiotic resistance. These findings suggest that in the future, the type of bacteria in the gut may help doctors choose the best treatment for each person.

Bipolar disorder is a very common and serious mental health condition that profoundly affects people’s mood, energy, and ability to carry out their daily activities. Despite being a well-known problem, it is still often misdiagnosed, which means that many patients do not receive the most appropriate treatment.

In addition, bipolar disorder is very complex: it manifests itself differently in each person, and medications that work for some may not work for others. One of the topics that has caught the attention of scientists in their quest to better understand this disorder is the relationship between the brain, the intestine and the microbiota, that is, the set of microorganisms that live in our digestive system.

This “brain-gut-microbiota axis” appears to play a role in bipolar disorder because it influences brain chemicals, gut hormones, and even the level of inflammation in the body. But how medications used for bipolar disorder alter these gut bacteria and how this affects treatment is still not entirely clear.

To try to answer this question, the researchers conducted a detailed review of previously published studies on the topic. They searched several reputable databases, such as PubMed and Scopus, and analyzed 314 studies in total. In the end, only 12 studies met the necessary criteria to be included in the review.

These studies involved adults diagnosed with bipolar disorder type I or II who were being treated with medications such as lithium and quetiapine. The studies compared treated and untreated patients, and also, in some cases, patients with bipolar disorder and healthy people.

The researchers used rigorous tools to assess the quality of the studies and the risk of error, and two experts independently collected the data to ensure the accuracy of the information.

The results showed that the medications used for bipolar disorder do indeed cause changes in the gut microbiota. For example, both lithium and quetiapine appear to increase certain bacteria that are considered good for gut health.

On the other hand, there was also an increase in bacteria linked to problems such as changes in metabolism and antibiotic resistance.

This means that while the drugs can help balance some body functions, they can also have undesirable effects on the gut and possibly other parts of the body. Interestingly, these microbiota changes were more pronounced in women.

In addition, in people treated with quetiapine, those who had greater improvement in depressive symptoms (so-called responders) had a microbiota profile more similar to that of healthy people and also showed patterns of brain function similar to those of people without the disorder.

Proposed effects of environmental factors on gut microbiome composition and neurochemical signaling in bipolar disorder. These imaging findings suggest that individuals who are nonresponders to quetiapine may have additionally abnormal serotonin (5-HT) signaling, leading to insufficient binding of quetiapine to key receptors. This dysfunction in the serotonergic system contributes to the observed persistent default mode network (DMN) hyperconnectivity, amplifying an already maladaptive neural state.

These findings help to better understand how treatment for bipolar disorder works in complex ways, affecting not only the brain but also the gut and its bacteria. This is important because the rise of antibiotic-resistant bacteria linked to metabolic disorders may pose long-term health risks.

Despite all this, the study had limitations: the methods used in the different studies were very varied, some had problems controlling factors that could confound the results, and there was a risk that some studies had analyzed the same people in more than one article.

Therefore, the scientists point out that new, better-controlled studies are needed to better understand how these changes in the microbiota influence the success of the treatment.

Still, the work highlights a promising path: in the future, it may be possible to use the profile of each patient's intestinal bacteria to create more personalized treatments, which bring more benefits and fewer side effects to those living with bipolar disorder.

READ MORE:

Pharmaco-psychiatry and gut microbiome: a systematic review of effects of psychotropic drugs for bipolar disorder 

Truong An Bui, Benjamin R. O’Croinin, Liz Dennett, Ian R. Winship, and Andrew J. Greenshaw

Microbiology. Volume 171, Issue 6 

https://doi.org/10.1099/mic.0.001568

Abstract: 

Despite being one of the most common and debilitating mood disorders, bipolar disorder is often misdiagnosed and undertreated. Its pathogenesis is complex, with significant patient variability and inconsistent treatment effectiveness. The brain-gut-microbiota axis plays a critical role in bipolar disorder by modulating neurotransmitter secretion, gut peptides and systemic inflammation. However, the mechanisms by which psychotropic treatments influence gut microbiota composition and their implications for clinical outcomes remain poorly understood. This systematic review evaluated the impact of psychotropic drugs on gut microbiota and their potential role in bipolar disorder treatment outcomes. A comprehensive search across Ovid MEDLINE, Embase, APA PsycINFO, Scopus and PubMed yielded 314 articles, of which 12 met the inclusion criteria (last search: 13 August 2024). The studies included were those on adults with bipolar disorder type I or II receiving psychopharmacological treatments; those with group comparisons (e.g. healthy controls vs. medicated vs. non-medicated) investigating gut microbiome changes; and no restrictions applied to psychotic features, comorbid anxiety or prior treatment responses. Exclusions involved individual case reports, incomplete conference submissions or early terminated studies lacking efficacy analysis. Cochrane ROBINS-I V2 tool was used to measure the risk of bias, and the GRADE approach was utilized to rate the certainty of evidence in included studies. Two authors independently extracted data into Excel spreadsheets, categorizing demographic and clinical characteristics, describing microbiome analytic methods and summarizing findings on gut microbiome changes post-treatment. Given the high variability in methods and outcome measures across studies, all details were reported without data conversion. Data synthesis reveals that psychotropic treatments, including quetiapine and lithium, influence gut microbiota by increasing the abundance of beneficial bacteria supporting gut health and pathogenic bacteria linked to metabolic dysfunction. Notably, female patients exhibited more significant changes in microbial diversity following psychotropic treatment. Additionally, patients treated with psychotropics showed an increased prevalence of gut bacteria associated with multidrug antibiotic resistance. In bipolar patients treated with quetiapine, responders – those experiencing improved depressive symptom scores – displayed distinct gut microbiome profiles more closely resembling those of healthy individuals compared with non-responders. Responders also exhibited neural connectivity patterns similar to healthy subjects. These findings underscore the complex dual impact of psychotropic medications on gut microbiota, with potential consequences for both gut and mental health. While the enrichment of beneficial bacteria may support gut health, the rise in antibiotic-resistant and metabolically disruptive bacteria is concerning. Study limitations include methodological heterogeneity, inclusions of other psychiatric disorders, a high risk of bias in some studies due to incomplete statistical analyses or insufficient control for confounding factors and potential duplication of study populations arising from overlapping authorship. Further research is essential to elucidate the functional consequences of these microbial shifts and their influence on treatment efficacy. Nevertheless, this review highlights the potential of utilizing gut microbiota profiles to inform personalized treatment strategies, optimize therapeutic outcomes and minimize side effects in bipolar disorder. This study was registered with Open Science Framework