Peter Lehman successfully defended his M.S. thesis this past June and completed the Pathology M.S. program. Peter’s thesis is entitled Effect of Gut Microbiota Modulation During Early-life and Adulthood on Host Immunity. He performed his thesis work in the laboratory of Dr. Ashutosh Mangalam where he examined the effects of gut microbiome disruption on immune function.

Humans have a symbiotic relationship with trillions of microbes living in the gut, where bacteria benefit from the host and vice versa. However, when the gut microbiota composition is altered, this relationship can be disrupted leading to an imbalance between disease-protecting vs. disease-promoting immune responses. In many cases, this imbalance can manifest as chronic inflammation or influence the outcome of human disease. Thus, it is crucial to understand factors that can modulate gut microbiota composition and influence host immunity. In this study, we sought to understand how a commonly used herbicide, glyphosate, can influence the adult microbiome and host immunity, and also how early-life antibiotic exposure affects host immunity later in life. In glyphosate-exposed adult mice, both gut microbiota composition and immune function were altered. Specifically, health-promoting bacteria (probiotics) such as Lactobacillus and Bifidobacterium species were decreased in glyphosate-exposed mice. Additionally, mice exposed to glyphosate showed enrichment of immune cells linked with inflammatory autoimmune diseases such as multiple sclerosis as well as markers linked with leaky gut. Similarly, early-life antibiotic exposure leading to complete microbiota depletion altered host immunity. Later in life, mice who were exposed to early-life antibiotics exhibited significantly increased small intestinal RORgt+ T cells and increased pro-inflammatory cytokine production from CD11c+ dendritic cells. These immunological changes were also associated with exacerbated experimental autoimmune encephalomyelitis (mouse model of MS) severity and increased autoreactive T cell proliferation later in life. These studies underscore the sensitivity of the immune system to alterations in the microbiome and the critical importance of maintaining a “healthy” gut microbiota. In addition to Dr. Mangalam, Drs. Kevin Legge and Thomas Waldschmidt served on his committee.

Importantly, the glyphosate section of Peter’s thesis was recently published in Environmental Toxicology and Pharmacology. The paper can be viewed at:

https://www.sciencedirect.com/science/article/pii/S1382668923000911?via%3Dihub