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From stress to science

THE WASHINGTON POST – When it comes to microbiome health, many people focus on the foods that will help the trillions of good bacteria in their guts thrive. But less is known about how other factors like stress and trauma influence our gut health.

A provocative study suggests that a mother’s stress may leave a lasting scar on future generations by impacting the makeup of her child’s gut microbiome.

The gut microbiome, a unique community of microorganisms, including bacteria, parasites and viruses that coexist in your intestinal tract, is gaining more attention for its critical role in both mental and physical health. Everyone’s microbiome is unique, influenced by what we eat, as well as our behaviours and environment.

The findings, though modest, add to a growing body of research in the nascent field of nutritional psychiatry, and could bring new attention to the brain-gut connection, particularly in the aftermath of trauma and adversity. Earlier research has established the importance of intestinal microbes that can influence a range of conditions, including depression, anxiety and heart disease.

The research, published last month in the journal PNAS, draws on a large, longitudinal study that looked at mothers’ experiences of mistreatment during their childhoods and their anxiety in pregnancy. Analysing that data, researchers found an association between maternal stress and the landscape of their children’s gut microbiome at two years old. The researchers also tracked children’s stress in early life and noted a correlation between certain inflammation-related gut microbes in the toddlers at two and increases in their mental health problems at four.

“Adversity tends to get under the skin,” said the study’s senior author and an assistant professor of psychology Bridget Callaghan at UCLA. “And this is yet another way we see adversity impacting individuals’ physiology.”

A NOVEL LOOK AT INTERGENERATIONAL TRAUMA

Research on how trauma and adversity is passed down through generations is not new. Ongoing studies are investigating the intergenerational transmission of trauma through various means, including genetics, learned behaviours and even the collective experiences of a group.

One of the novel aspects of the current study, Callaghan said, is that her team looked at the impact of adversity experienced by women that, in some cases, occurred even before their child was conceived.

PHOTO: FREEPIK

While rodent studies have documented the effects of a mother’s stress on the offspring’s microbiome, “no one has looked at how the scars of preconception adversity might be passed down and affect the microbiome in humans”, Callaghan added.

While the new study raises tantalising questions about the links between stress and the microbiome, it doesn’t provide definitive answers, and some experts are sceptical of the findings.

For example, researchers did not determine that the transmission of trauma runs directly from the mother’s microbiome to the child’s. That pathway is possible, since infants acquire their first gut microbes passing through the mother’s birth canal and from breast milk, Callaghan said. But it is far more likely that transmission occurs through other biological or behavioural paths.

“I think the most likely scenario is that the impacts of adversity on moms’ mental and physical health and likely parenting behaviors are impacting the next generation,” she said.

“And that stress is affecting the next generation’s microbiome.”

A LOOK AT THREE ‘ADVERSITY EXPOSURES’

The research analysed data collected as part of a study of 450 pairs of mothers and children living in Singapore, known as GUSTO, or Growing Up in Singapore Towards Healthy Outcomes.

Faecal samples from the children were collected at age two and analysed to determine the composition of the child’s microbiome. Callaghan and her colleagues focused on three distinct moments of “adversity exposure” experienced by both mother and child, including:

– Mistreatment of the mother during her childhood, including physical, sexual or other abuse or neglect.

-The mother’s anxiety during pregnancy.

-The child’s early exposure to stressful life events, such as divorce or the death of a grandparent.

As part of the study, researchers also accessed information on children’s social and emotional well-being at two and four years old, tracking issues such as sleep problems, social difficulties, anxiety, depression, and aggressive or antisocial behaviour.

Researchers reported finding “distinct differences in gut microbiome profiles linked to each adversity exposure.” In other words, children of mothers who had been abused or neglected all had a similar pattern of microbes. Children who experienced anxiety in utero had a different microbial signature, as did the microbiomes of children who had lived through stressful events.

HOW STRESS CAN ‘SHIFT THE BALANCE’ OF GUT MICROBES

Professor Christopher Lowry at the University of Colorado at Boulder who studies how stress impacts the gut microbiome and overall health, said the new research “breaks ground in several important ways,” including adding to our understanding of the effect of transgenerational, prenatal and early postnatal adversity on a child’s gut microbiome. The study also suggests that certain types of bacteria are associated with a young child’s social and emotional development.

Lowry said the study adds to previous research findings that maternal or early-life stress can “shift the balance” of gut microbes from those that have anti-inflammatory effects toward those associated with inflammation.

The finding that adversity during the first two years of life was associated with decreases in the diversity of the child’s gut microbiome is important, he said. High diversity is a critical feature of a healthy gut microbiome, and the study suggests that “stress exposures reliably decrease diversity of the gut microbiome throughout the life span”, he said.

HOW DIFFERENT GUT MICROBES AFFECTED CHILDREN’S HEALTH

Specifically, the study found that the microbe Clostridium sensu stricto, an inefficient producer of an important anti-inflammatory compound called butyrate, was more abundant among children whose mother’s had higher preconception adversity. And a more efficient butyrate producer, Ruminococcus, was less abundant among these children.

Prenatal stress in the mother and stressful events in the child’s early life was associated with increased levels of the microbes Finegoldia and Streptococcus, which have been implicated in inflammation, and with decreased abundance of anti-inflammatory-associated microbes Parabacteroides and Intestinibacter, researchers report.

When researchers looked at the children’s behaviour and emotional well-being, they found that lower levels of Intestinibacter at two years old were associated with more anxiety and depression at four years old; fewer Coprobacillus, Lachnospiraceae UCG-008 and Faecalibacterium at two was associated with more sleep problems at four. And more Veillonella and Blautia at two years old was associated with more sleep problems at four.

SCEPTICISM ABOUT THE FINDINGS

Professor of computational biology and bioinformatics Curtis Huttenhower at the Harvard TH Chan School of Public Health, said that the study touches on “several important and provocative topics” related to the microbiome, but that he felt the research was limited for a number of reasons.

He noted that the study doesn’t “establish a means” by which a mother passes on the effects of adversity to her child’s microbiome. He also noted that mothers have a relatively small influence on a child’s microbiome and that infants acquire the majority of their microbes from many other sources, including fathers, other family members and their general surroundings in early life.

The study mainly investigated “very summarised, high-level information” from the microbiome, he wrote in an e-mail. “Most of the microbes mentioned individually actually represent very diverse groups of multiple organisms, which can’t be summarised accurately into simple behaviours,” he said.

Callaghan agreed that because the study relied on microbiome data at the genus level, its findings on the functionality and impact of specific bacterium are limited. Still, she added, the microbes noted in the study play some role in the inflammation or immune response, and these changes in the type and quantity of microbes could be one way that adversity or trauma affects a child’s social, emotional or mental well-being.

The study, a retrospective analysis that showed correlations only, has other limitations. Much of the data relied on mothers’ memories of their own and their children’s early experience, which can be unreliable.

The research only focused on mothers and did not examine the influence fathers might have on the composition of a child’s microbiome. All of the participants were Chinese, Indian or Malaysian, which could make the findings less applicable to other groups because different cultures have unique diets and ways of dealing with stress that shape the microbiome.

Assistant professor Jotham Suez at the Johns Hopkins Bloomberg School of Public Health who studies the microbiome and its role in human health and disease, said the study results, while “interesting,” should be interpreted with “caution.” He added that the correlations and effect size are weak.

“The altered microbiome may impact well-being and mental health of the child, but there are no data to support that in this paper,” Suez said in an e-mail.

Even so, there’s no dispute that a healthy gut microbiome can lead to better overall health.

To that end, Callaghan said, the study’s findings could help direct health providers and public health advocates to tailor more microbiome-specific interventions, such as nutrition, probiotics and prebiotics.

“There are things we can implement at a societal level – like access to nutritionally dense foods that we know would positively impact the microbiome,” Callaghan said. “If those types of changes could also address some of the impacts of adversity across generations, that would be really powerful.” – Rachel Zimmerman

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