Hurricane Harvey caused record-breaking, catastrophic flooding across the city of Houston. After floodwaters receded, several health concerns arose, including the potential adverse impact of exposure to mold in flooded homes. We rapidly launched the Houston Hurricane Harvey Health Study to evaluate if microbiome sampling in the wake of a disaster could inform flood-associated environmental exposures and adverse health outcomes. We enrolled a total of 347 subjects at 1-month and 12-months post-Harvey, collecting human (stool, nasal, saliva) and environmental (house swab) samples to profile the bacterial and fungal microbiota. Here we show reported exposure to mold was associated with increased risk of allergic symptoms for up to one year post-disaster, and that butyrate-producing bacteria in the gut were linked to protection from allergic symptoms in mold-exposed individuals. Together, these data provide new insights into how microbiome:environment interactions may influence health in the setting of a flood-related disaster.