Does stress early in life leave an imprint in our guts? The gut microbiome and mental health.

We all experience stress.


Whether garden-variety stressors (the task that was due last week, the pile of laundry that keeps growing, the traffic jam when you’re running late), more serious ones (living through a natural disaster like a hurricane or flood, experiencing an assault) or chronic ones (caring for an ill relative, being unemployed, living with someone who is abusive), each of us faces stress from time to time.

Depending on the stressor’s severity, how we experience it, and how long it lasts, it can affect our bodies and brains differently.

A short-term stressor, like getting caught in traffic, might increase your blood pressure and have you feeling frustrated or annoyed for a few minutes.

A more chronic stressor that lasts weeks or months can impair your immune function or result in symptoms of clinical depression or anxiety.

But do we ever stop to think about how stress might affect our guts?

Not the stomach-in-knots feeling that you might get when you’re stressed. But the actual bacteria inhabiting our bowels.


Your intestines are home to trillions of bacteria, that together weigh in at around three pounds! These bountiful bugs that make up the gut microbiome may be sensitive to stress, too. In rodents, even brief mild stress changes the composition of gut bacteria, as does chronic stress.

However, there is less research on stress impact on gut microbiome in humans.

The gut microbiome is the collection of microbes (bacteria, archaea, viruses, plus their genetic material) in the gut.


Normally, there is a balance of different bacteria types (or taxa, e.g. genera, species, subspecies), in the human gut. Based on the animal research, scientists wonder whether stress also alters the balance of gut bacteria in humans.


Adults with major depression, a common companion of stress, have altered gut microbiome composition. However, in healthy adults, stress levels are not associated with gut microbiome composition, suggesting that we need to learn more about how the type, timing and severity of stress impacts the gut microbiome in humans.


One particularly pernicious form of stress is early life stress (also referred to as adverse childhood experiences or “ACEs”). This includes abuse, neglect, or a chaotic home environment during childhood or teenage years.

In the past decades, we’ve learned that such early life stress can increase risk for everything from depression to heart disease, even if the person has overcome the stressful environment of their youth.


This is likely because the stress has occurred during a sensitive period of brain and body development, when our stress response axis is developing — disruptions here can set us up for vulnerability to stress down the road.


But is the same true for the gut?


If our bowel bacteria are sensitive to stress, does the stress we experienced early in life leave an imprint in our guts? This is the sort of question that I am interested in answering in my research.

In rodents, early life stress changes the composition of the gut bacteria, which lasts through adulthood. I was interested in whether the same were true in humans.

In our laboratory at the University of Pennsylvania, we focus on how stress impacts the body and brain, and are interested in how different types of stress, such as early life stress, might increase risk for mental health issues.


We recruited healthy women to our laboratory to look at whether their early life experiences had left a signature, decades later, in their gut microbiota. These women, who were pregnant at the time of the study, were otherwise physically and psychiatrically healthy. Half of them had experienced multiple childhood stressors, and half had not.


We found that the women who had multiple stresses in early life have a different looking gut microbiome than women without such experiences.


Specifically, the women with high levels of early life stress have elevated gut Prevotella compared with women without early life stress. This is interesting, as studies by other research teams have shown that this type of bacteria is associated with inflammation and differences in emotional processing in the brain. (Specifically, researchers found elevated Prevotella in people with rheumatoid arthritis, a disease in which the joints are inflamed, and in people with lower activity in a brain region called the hippocampus when viewing negative images).


We also found that specific gut taxa, including Prevotella and Dialister, are associated with cortisol and inflammatory response to an acute stress administered in the lab, in both groups of women. To examine this, we asked a subgroup of our participants to perform a stressful public speaking exercise, and measured levels of cortisol (a stress hormone) and proinflammatory cytokines (substances secreted by immune cells that cause inflammation) in their blood. We were interested in this because elevated levels of cortisol or proinflammatory cytokines, over months or years, can have negative impacts on our health. Also, we and other researchers have found that adults with a history of early life stress have an altered stress response system (including cortisol and cytokine output), but no one had looked at this in the context of the gut microbiome.


Why is this important?


This is the first study to show that stress experienced early in life may impact adulthood gut microbiome in humans, and the first to find that a more intense response to stress is associated with abundance of particular microbes in the gut.

While these are exciting initial results, more studies are needed in this area.

As luck would have it, another study came out on the heels of ours that added more detail to the picture. This study looked at shorter-term effects of childhood stress on the gut microbiome, that is, when subjects were adolescents rather than adults.

Dr. Bridget Callaghan examined the microbiota of teens who had lived in an orphanage in early life (a form of severe chronic stress) and compared it with the microbiota of children who had been raised in a stable family environment.


The children were raised in orphanages were on average from birth to roughly age 3, although some remained in institutional care through age 7. When these children were studied a few years later, at around age 10–15 years, they had altered gut microbiota compared with the children who had spent their entire lives in a stable family environment.


Together, these results indicate that early life stress can impact the gut microbiota during childhood, which can persist through adolescence and into adulthood.


These initial results need to be replicated by other researchers, and there are many related questions that need to be addressed. For instance, if early life stress does leave a permanent mark on the gut microbiome, does this translate to health or mental health risk in adulthood? If so, what role does the gut microbiome play in the link between early life stress and adulthood health risks? Are there ways we might intervene at the gut microbiome level, via diet or other factors, to help offset some of the impact of early life stress?

Finally, do factors such as resilience or having a supportive adult present buffer some of the effects of early life stress on the body and brain?


 

NOTE FROM THE EDITORS: We are so excited to have Dr Liisa Hantsoo writing for InSPIre the Mind. Liisa is an Assistant Professor at the Department of Psychiatry, Penn Center for Women’s Behavioural Wellness at The University of Pennsylvania School of Medicine. We are so pleased that Liisa wanted to share an insight into her work in childhood adversity, the gut microbiome and inflammation with us.


 




header image source: Jukan Tateisi on Unsplash