Effect of gut microbiota modulation during early-life and adulthood on host immunity

Humans and trillions of microbes (gut microbiota) living in the gut have a symbiotic relationship where gut bacteria benefit the host and vice versa. However, when gut microbiota composition is altered, this symbiotic 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 the factors that can modulate gut microbiota composition and their influence on host immunity. In this study, we sought to understand how a commonly used herbicide, glyphosate, influenced adult microbiota composition and host immunity and how early-life antibiotic exposure affects the host immunity later in life. In glyphosate-exposed mice, both gut microbiota composition and function were altered. Specifically, health-promoting bacteria (probiotics) such as Lactobacillus and Bifidobacterium species were also decreased in glyphosate-exposed mice. Additionally, mice exposed to glyphosate showed enrichment of immune cells linked with inflammatory autoimmune diseases such as multiple sclerosis and 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 antibiotics exhibited significantly increased small intestinal ROR_γt+ T cells and increased pro-inflammatory cytokine production from CD11c+ DCs. These immunological changes were also associated with exacerbated experimental autoimmune encephalomyelitis (EAE) severity and increased autoreactive T cell proliferation later in life. These studies underscore the immense sensitivity of the immune system and, thus, highlight the critical importance of maintaining a “healthy” gut microbiota where exposure to a commonly used environmental toxicant or early life microbiota modulation can have significant effects on host immunity.