Researchers explore link between microbiome and prenatal depression
Part of CCTS's Works in Progress series
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Depression during pregnancy and in the postpartum period affects more than 20 percent of pregnancies worldwide. In addition to morbidity for both the mother and child, prenatal depression is also associated with negative health outcomes in childhood, including attention-deficit disorder, autism spectrum disorder, and depression.
Multiple studies have demonstrated that gut microbiota and mental health are linked through the microbiome-gut-brain axis. Now, a CCTS funded pilot study led by Michael Ragozzino, professor of psychology at the University of Illinois Chicago, is further exploring the connection between the microbiome and prenatal depression through fecal microbiota transplants.
Cause or consequence
Previous research has revealed that depression is the most common complication of pregnancy and disproportionately affects low-income women of color, particularly non-Hispanic Black, Latina, non-Hispanic Asian, and Native American women. This is often due to a lack of access to treatment, lack of screening, and inefficient care models.
The need for better prevention and more accurate diagnosis of perinatal mental health problems led co-investigator and assistant professor of biomedical engineering, Beatriz Peñalver Bernabé, together with Dr. Pauline Maki, to create a clinical research study called Moms and Mental Health, or MoMent. The study uses clinical data and biological samples to examine the connection between gut microbiota and mental health, which lays the foundation for the pilot project.
“If you look at the data, the gut microbiota when the baby is born looks like the gut microbiota of the mom. What they get is whatever microbiota you have,” said Peñalver Bernabe. “What if we can modify the microbiota of a pregnant individual that we know is at high risk of developing depression later on?”
With this question in mind, the pilot study will collect fecal samples from pregnant individuals who have received a diagnosis of perinatal depression, treat these samples in the laboratory, and inject them into germ-free mice. The team will then examine the mice to see if this transplant produces a microbiome that looks like the individual with depression or if it produces behavioral changes that look like depression.
“Bea has human clinical data related to perinatal depression showing that alterations in the gut microbiome are related to depression in the perinatal period- that could be during pregnancy or right after pregnancy,” said Ragozzino. “One of the key questions is: is the alteration in the gut microbiome causal, or is it a consequence of depression? The preclinical work allows you to manipulate the system and actually determine causality.”
The invisible organ
These days, microbiome research features heavily in headlines, including stories about the critical role bacteria plays in human physiology, immunology, and metabolism. Jun Sun, professor in the division of gastroenterology and hepatology, compares the microbiome to an invisible organ and fecal transplantation to organ transplantation.
“I look at the microbiome in different perspectives of disease. I look at inflammation, cancer, and also infection. Basically, we are dealing with some invisible organ which we haven’t really known in the past because we were limited with tools, with technology, and also with knowledge,” said Sun.
Sun, a co-investigator on the pilot project, runs UIC’s Gnotobiotic Mouse Facility. This facility is integral to the preclinical study, as the mice in the germ-free breeding laboratory are born and raised in absence of live microbes.
“These mice don’t have any microbiome, so they’re kind of starting from scratch,” said Sun. “If the team is able to establish a preclinical to humanized-use model, there is the potential to implant any human microbiome into germ-free mice. We know the significance and the impact, not just for the depression field but also for other diseases. That’s why we are quite excited about what we are doing.”
Addressing the barriers to translation
While the pilot study draws upon a body of existing research and clinical data, Ragozzino said the partnership was new for this particular team. He credits graduate student Ainsley Tran for driving the collaboration.
“Graduate students are often the facilitators of collaborations. Ainsley is on the ground doing a lot of the work in the Gnotobiotic Facility working with the germ-free mice and doing the behavioral testing,” said Ragozzino.
Even with stable support in the laboratory, the collaboration is not without its challenges. A significant hurdle is recruiting and retaining enough participants to power the results of study examining microbiota.
“When you look at the microbiome, you need at least 200 people longitudinally. We are very good at retaining people; we develop very good rapport with the participants,” said Peñalver Bernabe. “But getting participants is tough, especially because we are not a clinical group, we are a research group. We are trying to work with the people in obstetrics, to be more embedded there, so we can have better access to the patients.”
The next generation
The data set associated with this project has the potential to tackle not only mental health, but other kind of perinatal conditions, such as gestational diabetes, preeclampsia and obesity.
“Any kind of problem during pregnancy, we will be able to use our models and our data and translate it using basic research and the germ-free facility. And any expert in the field that is interested can do that as well,” said Peñalver Bernabe.
The team also believes probiotics or prebiotics- even fecal transplants in the future- could be seen by mothers as a more natural alternative to pharmaceutical interventions while pregnant. Studies have revealed a resistance to pharmaceutical treatment during pregnancy due to the potential impact on the fetus, but a lack of treatment can have serious negative consequences to both mother and child. Manipulating the mother’s microbiome could provide a more beneficial microbiome product to the fetus during pregnancy.
Sun said, “Because patients usually hesitate to use prescription drugs, if we know what kind of microbiome potentially contributes to the risk of offspring with the potential for neurogenerative challenges, [the mother] could consider using some probiotic or prebiotic or even change their diet.”
From Ragozzino’s perspective as a neuroscientist, he is interested in the potential implications of the microbiome on brain development, including neuroinflammatory changes that could alter the course of development. Future stages of translation would include examining the health outcomes of the babies delivered by the transplant recipients and the potential effect of this “invisible organ.”
“A significant number of individuals diagnosed with autism have gastrointestinal problems. I don’t think that’s by chance,” said Ragozzino. “Ultimately, we don’t want to give treatments chronically. We want to see whether we can give things at an early developmental stage or actually prevent it.”
“This collaboration allows us to go further and look at how the microbiome potentially could affect not just the individual but how it affects the next generation,” said Sun.