A major focus of the Mangalam Lab’s work is determining how environmental contaminants alter the gut microbiome and thereby influence host immune responses. In collaboration with Dr. Hans-Joachim Lehmler, the Mangalam Lab has used glyphosate as a model environmental toxicant. Glyphosate is particularly interesting because its primary biochemical target, the shikimate pathway, is absent in mammalian cells but present in many microbes including gut bacteria. Dr. Mangalam and collaborators demonstrated that chronic low-dose glyphosate exposure disrupts gut microbial communities, including depletion of beneficial bacteria such as Lactobacillus and Bifidobacterium, and is accompanied by increased colonic IL-17A–producing CD4 T cells and elevated lipocalin-2, a marker of intestinal inflammation. These findings support the concept that the microbiome can serve as an important intermediary through which environmental exposures alter immune homeostasis and contribute to chronic inflammatory conditions.
The Mangalam Lab’s environmental health research builds on a broader program examining how microbiome dysbiosis contributes to immune-mediated disease. Dr. Mangalam and colleagues were among the first groups in the United States to demonstrate that people with multiple sclerosis (MS) harbor a distinct gut microbiome, characterized by depletion of potentially beneficial bacteria and enrichment of inflammation-associated taxa. Subsequent studies from our laboratory showed that bacteria involved in the metabolism of dietary phytoestrogens, including Prevotella, Parabacteroides, and Adlercreutzia, are depleted in MS. Using mechanistic animal models, the Mangalam Lab demonstrated that restoration of these bacteria and their dietary substrates can promote regulatory immune responses and suppress neuroinflammation. The Mangalam Lab also identified human-derived beneficial bacteria, including Prevotella histicola, that can induce regulatory T cells and ameliorate disease in experimental models of MS.
Together, these studies support two interconnected themes in our laboratory: (1) defining how environmental exposures, diet, and host factors disrupt beneficial microbial communities and promote inflammatory states, and (2) identifying beneficial microbes, microbial functions, and metabolic pathways that can be leveraged to restore immune homeostasis. Ongoing work is examining how glyphosate-induced microbiome disruption may contribute to chronic inflammation, adipose tissue inflammation, obesity, and metabolic syndrome, and whether microbiome-directed interventions can mitigate these effects.
The Mangalam Lab’s long-term goal is to define the microbiome-mediated mechanisms that connect environmental exposures to disease and use this knowledge to develop microbial biomarkers, targeted microbiome interventions, and strategies that preserve or restore beneficial microbial functions without broadly disrupting the microbial ecosystem.