<p>With rapidly growing cities and industrial development, urban air pollution and heavy metal exposure have become prominent environmental and human health issues. Numerous airborne contaminants such as particles, nitric and sulfur oxides, ozone, lead, cadmium, mercury and arsenic, have been associated with lung diseases, gastrointestinal system problems, cardiovascular diseases, kidney diseases, metabolic diseases and immune diseases. Furthermore, the toxins in our environment can modify the human microbiota and then disrupt physiological homeostasis by inducing dysbiosis. In this narrative review, we summarised the impacts of urban air pollution and heavy metal exposure on human microbiota and multisystem physiology, emphasizing the role of the gut-lung axis. The mechanisms underlying the association between environmental toxins and altered respiratory and gastrointestinal microbiota were discussed. Oxidative stress, chronic inflammation, epithelial barrier defects and immune dysfunction were all involved in the effect of airborne pollutants on microbiota. Dysbiosis of the gut-lung axis was reported to result in respiratory and gastrointestinal diseases, cardiovascular system dysfunction and kidney damage. Clarification of the interplay between environmental toxins, microbiota dysbiosis and multisystem physiology provides promising opportunities for devising novel prevention and treatments for air pollutant-induced diseases. Reducing the environmental exposures and recovering microbial balance should be regarded as alternative approaches for improving health.</p>