For years, scientists have known that early life stresses have lasting effects on both humans and animals. This trauma can manifest in a number of ways, including disruptions in emotional and physical development, impairments in cognitive function and an assortment of metabolic disorders.
While much research has been devoted to better understanding the toll of early life stresses more broadly, an understudied area is related to gut health and how it affects immune system function.
In humans, these issues can result in an increased risk of disease development, ranging from irritable bowel syndrome and Crohn’s Disease to cancers and hypertension. For animals, especially those involved in agriculture, there are implications on well-being, longevity and productivity.
Adam Moeser, a professor and the Matilda R. Wilson Endowed Chair in the College of Veterinary Medicine, is uncovering groundbreaking answers to questions surrounding early life stress.
Moeser has spent years investigating how early stress rewires the body, specifically through the gut. His work focuses on understanding how early life adversity and stress influence the development of brain-gut axis communication and disease risk across the entire lifespan.
In previous research, his team has shown that early life adversity can permanently alter gut function, triggering chronic gastrointestinal diseases with potential systemic effects, including impacts on the brain and mental health disorders.
His latest work — backed by MSU AgBioResearch, the National Institutes of Health, USDA and animal industry groups — reveals how stress reprograms immune cells called mast cells, key players in the gut-brain connection.
“These immune cells are found throughout the body and play a critical role in immune regulation, but their dysregulation can contribute to inflammatory and stress-related diseases,” Moeser said. “These findings extend beyond agricultural animals by offering crucial insights into human health, disease prevention and the importance of early life care.”
In total, Moeser has published more than 100 peer-reviewed articles in prestigious academic journals and has established himself as a world-renowned leader in gastrointestinal biology, stress physiology and mast cell research.
Understanding the role of stress, biological sex on development
A recent study conducted at the MSU Swine Teaching and Research Center and published in 2023 in Scientific Reports focused on early weaning in pigs — a common agricultural practice used to optimize reproductive efficiency.
Moeser and his colleagues examined how early life stress and biological sex influenced long-term immune responses. While early weaning has economic benefits, it is also a well-known stressor for pigs, involving maternal and littermate separation, environmental changes, dietary shifts and increased exposure to new pathogens.
Moeser said the study was the first comprehensive investigation into how early life stress interacts with biological sex to shape long-term immune function. The team found that early weaning had lasting effects on immune responses to both vaccination and exposure to lipopolysaccharide, a bacterial component used to model immune challenges.
The team also uncovered that early weaned female pigs had the strongest immune responses as compared to the other groups, including early weaned castrated males.
“This suggests that early life stress leads to different immune system priming in females and may increase their risk of chronic inflammation,” Moeser said. “In contrast, male castrates displayed an overall blunted immune reaction to early weaning stress, potentially contributing to their higher mortality rates.
"The female-biased immune reactivity in our study runs parallel to existing literature in humans. There are several factors that may contribute to these differences, including the influences of X chromosome-linked genetic factors and sex hormones, like testosterone and estrogen.”
Moeser said it’s crucial for producers to consider several elements, including the age of weaning, genetic background and castration when developing strategies to enhance health and productivity in pigs. He emphasized the significant implications for human health.
"We're studying how castration and hormonal shifts shape the immune system in male pigs,” Moeser said. “The goal is to better understand how these changes impact health and productivity while also shedding light on similar processes in humans. By looking at early life stress and sex differences, we are hoping to develop practical strategies to improve animal and human health and well-being.”
Rebecca Robbins, a veterinarian and swine health and reproduction expert, has served as a research partner with Moeser. She currently works for the Pig Improvement Company, a worldwide leader in swine genetics.
“Dr. Moeser relentlessly investigates gut health and early life environmental and host factors to enhance swine producer understanding of the impact of management practices on immediate and long-term disease susceptibility,” Robbins said. “His research on weaning age and gut development has revolutionized our thinking about how to approach management of the post-weaning pig and has provided critical insights into strategies to manage conditions like diarrhea and weight loss during that sensitive period of a pig’s life.
“I believe that the basic science and physiologic mechanisms being researched in Dr. Moeser’s lab have future implications on the development of precision livestock farming tools to ensure all pigs express their full genetic potential.”
This story originally appeared on the AgBioResearch website.
