Mom’s gut biome

Here, I present two studies of the gut biome. First, Eisenstadt published “How a Mother’s Microbiome Helps Shape Her Baby’s Development” on the Broad Institute (2022) on the Broad Institute website, citing Vatanen, Jabbar et al. (2022) “Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism” in Cell. I like this article because it provides helpful background to a study that would otherwise be quite daunting for me. I am a developmental psychologist by training and love new research on sneaky mother-child connections. Here’s an edited version of the article:

During and after child birth, bacteria from the mother’s gut take up residence in the baby’s body, seeding a unique community of beneficial bacteria that will help break down food, synthesize vitamins, and help teach the baby’s nascent immune system to recognize foreign organisms.

A mother’s microbial gifts go even further than that, according to a new study from scientists at the Broad Institute of MIT and Harvard. They explored how the microbiomes of the mother and baby change during pregnancy and the first year of life, and discovered that some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows.

Appearing in Cell, the study is the first to uncover large-scale “horizontal gene transfer” events between different species of maternal and infant gut bacteria. The research also revealed a wide range of chemicals produced by the bacteria, or metabolites, that are unique to the baby. Together, the findings add to a growing appreciation for the complex physiological connection between mother and infant during early life.

“This study helps us better understand how the rich community of microbes in the gut initially forms and how it develops during infancy,” said Tommi Vatanen, a co-first author on the study. “The microbiome is very dynamic and develops along with other systems, so there’s a lot going on in the first years of life.”

“Our work presents a unique perspective of core development of the infant gut microbiome and metabolome under influence of the mother’s factors, with profound implications for immune and neurological development,” said senior author Ramnik Xavier. Xavier and his lab first began studying the microbiome at the Broad eight years ago. Since then, they have investigated how gut bacteria fluctuate during early life, how early microbiome colonization influences risk for immune-related diseases like type 1 diabetes, allergy, asthma and inflammatory bowel disease, and how the microbiome varies in different places around the globe.

In this new study, Xavier and his team aimed to more deeply explore the development of the microbiome during the first year of life. They sequenced bacterial DNA from stool samples from 70 mother-child pairs collected during late pregnancy through various stages of infancy.

In the infant gut bacterial genomes, the researchers pinpointed hundreds of genes that had originated in maternal bacteria. This indicates that the bacterial horizontal gene transfer from mother to baby isn’t a one-time event at childbirth, but an ongoing process throughout the baby’s first year of life.

Among the shared genes the team identified are many that encode proteins related to the infant diet, such as enzymes that break down complex sugars in breast milk. “There seems to be a clear benefit to this gene transfer, in that it provides important functions to the new bacterial species in the baby,” said Vatanen.

The donor bacterial strains can share their genes without colonizing the baby’s gut, so more work is needed to figure out where and when this gene transfer is occurring. In addition, the scientists acknowledge that the infant’s microbes might also be acquiring genes from other people in its daily life, such as the nonbirthing parent, siblings, or grandparents, so there may be even more horizontal gene transfer events than they’ve been able to capture so far.

To better understand the biological functions of the changing microbiome in the mother and baby, the researchers also examined microbial metabolites — substances produced or converted by microbes that can have effects throughout the body. In the mothers during and after delivery, the researchers observed changes in their microbiome and metabolome that could potentially affect maternal metabolic health, such as an increase in steroid compounds that have been linked to impaired glucose tolerance.

In the metabolomic profiles of young, breastfed infants, the scientists found substances known to boost inflammation in disease, suggesting that in very early life, the metabolites promote healthy maturation of the immune system. “In many ways, inflammatory markers can educate the immune system so that it’s better prepared to resist toxins or bad bacteria and shows more resilience when it’s perturbed,” said Xavier. The metabolomic profiles of infants fed regular (not hydrolyzed, i.e., hypoallergenic) formula were distinct from those of breastfed babies, including metabolites that may contribute to risk for immune-related diseases such as type 1 diabetes and asthma.

 “We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said Xavier. “This may be yet another benefit of prolonged bonding between mother and child, providing more chances for these beneficial gene transfer events to occur.”

I love this study because it highlights ways in which maternal prenatal health impacts infants, both in terms of resistance to disease and the benefits of breast feeding to reduce likelihood of Type I diabetes and asthma. It suggests some good questions to ask about maternal prenatal care and diet as well as breastfeeding.

Second, the Harvard Gazette (April 23, 2023) published “Expanding Our Understanding of Gut Feelings.” Here’s the slightly edited article with some bold:

A new study of more than 200 women by investigators from Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health details links between specific gut bacteria and positive emotions like happiness and hopefulness. The results were published in Psychological Medicine.

According to past research, the brain communicates with the gastrointestinal tract through the gut-brain axis. One theory is that the gut microbiome plays a starring role in the axis, linking physical and emotional health.

“Many studies have shown that disturbance in the gut microbiome can affect the gut-brain axis and lead to various health problems, including anxiety, depression, and even neurological disorders,” said co-corresponding author Yang-Yu Liu, an associate scientist at the Brigham and an associate professor at Harvard Medical School.

“This interaction likely flows both ways — the brain can impact the gut, and the gut can impact the brain,” said first author Shanlin Ke, a postdoctoral researcher in Liu’s lab. “The emotions that we have and how we manage them could affect the gut microbiome, and the microbiome may also influence how we feel.”

The gut-brain axis might affect physical health, as well. Past research has shown that positive emotions and healthy emotional regulation are linked to greater longevity. In contrast, negative emotions are linked to higher rates of cardiovascular disease and mortality from all causes, according to Laura Kubzansky, a professor in the Chan School’s Department of Social and Behavioral Sciences and co-corresponding author of the new research.

“The brain can impact the gut, and the gut can impact the brain.”

The new study included women from a mind-body sub-study of the Nurses’ Health Study II. These middle-aged, mostly white women filled out a survey that asked about their feelings in the last 30 days, asking them to report positive (feeling happy or hopeful about the future) or negative (sad, afraid, worried, restless, hopeless, depressed, or lonely) emotions. The survey also assessed how they handled their emotions. The two options were reframing the situation to see it in a more positive light or suppressing negative emotions.

Three months after answering the survey, the women provided stool samples, which were analyzed using metagenomic sequencing. The team compared the results from the microbial analysis to the survey responses about emotions, looking for connections.

“Some of the species that popped up in the analysis were previously linked with poor health outcomes, including schizophrenia and cardiovascular diseases,” said co-first author Anne-Josee Guimond, a postdoctoral researcher in Kubzansky’s lab. “These links between emotion regulation and the gut microbiome could affect physical health outcomes and explain how emotions influence health.”

The analysis found that people who suppressed their emotions had a less diverse gut microbiome. The investigators also found that people who reported happier feelings had lower levels of Firmicutes bacterium CAG 94 and Ruminococcaceae bacterium D16. On the other hand, people who had more negative emotions had more of these bacteria.

“I was intrigued that positive and negative emotions often had consistently similar findings in opposite directions,” Kubzansky said. “This is what you would expect, but kind of amazing to me that we saw it.”

The researchers also examined what the microbes in the gut were doing on a functional pathway level, looking for links between changes in the capacity of this activity and specific emotional states and emotion regulation methods. They found that negative emotions were linked to lowered capacity activity in multiple metabolism-related actions.

The researchers hope to repeat the study with more diverse populations, a more extensive emotional survey, and longitudinal data. A more specific analysis of the microbial strains might also help develop microbiome-based therapeutics like probiotics to improve emotions and well-being.

I love this study because it reflects the complex brain-body interactions that make it clear why the study of adverse childhood experiences (ACEs) appeals to mental health professionals and medical professionals. It also makes clear why multidisciplinary approaches are essential to helping people.