The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity.

Orthopoxviruses can transmit via inhalation of virus-laden airborne particulates, with the initial infection triggered along the respiratory pathway. Understanding the flow physics of inhaled aerosols and droplets within the respiratory tract is crucial for improving transmission mitigation strategies and elucidating disease pathology. Here, we introduce an experimentally-validated physiological fluid dynamics model simulating inhaled onset of smallpox caused by the variola virus of Orthopoxvirus genus. Using high-fidelity Large Eddy Simulations, we modeled inhaled airflow and particulate motion within anatomical airway domains reconstructed from medical imaging. By integrating these simulations with viral concentration and individual immune factors, we estimated the critical exposure durations for infection onset to be between 1−19 hours, aligning with existing smallpox literature. To formalize the broader applicability of this framework, we extended our analysis to mpox virus, a circulating pathogen from the same genus. For mpox, the mechanophysiological computations indicate a typical critical exposure duration of 24−40 hours; however, this can vary significantly–from as short as 8 hours to as long as 127 hours–depending on virion concentration fluctuations within inhaled particulates, assuming happenstance of viral evolution. Predictably longer than the critical exposure durations for smallpox, the mpox findings still strongly suggest the possibility for airborne inhaled transmission during prolonged proximity.