Exploring the link between rural aerobiomes and the geographic variability seen in inflammatory bowel disease: mechanistic insights from a novel animal model

Abstract Introduction Ulcerative colitis (UC) is characterised by an abnormal immune response to the microbiome in genetically predisposed individuals. Epidemiological studies indicate that those residing in rural areas experience lower incidence of UC, potentially attributable to exposure to soil-associated bacterial species. The recently characterised aerobiome (microbial species found in air) reflects local topography, yet its role as a vector for gut colonisation remains unestablished. We hypothesise that the aerobiome serves as a vector for colonisation and that exposure to a soil-based aerobiome confers protection in a murine model of UC. A secondary objective was to assess whether timing of exposure during infancy influences this protective effect—a period known as the critical window of opportunity of immune system priming. Methods Custom-designed cages enabled creation of a “super clean” (SC) environment for BALB/c mice, with the aerobiome as the sole variable. Bacillus strains genetically modified to express green fluorescent protein were initially utilised to assess aerobiome driven colonisation and validate this novel experimental system. Mice were bred in-house and divided into three groups: (i) SC, (ii) urban aerobiome, and (iii) rural aerobiome ( N = 8–12 per group, males and females). For the secondary outcome, a crossover design was implemented (e.g., rural aerobiome from birth switched to SC at 8 weeks, and vice versa). At 14 weeks, DSS-induced colitis resembling UC was initiated. Clinical, endoscopic, biochemical, pathological, and metagenomic parameters were assessed. Results Exposure to a soil-based rural aerobiome resulted in distinct modulation of the microbiome, notably the emergence of butyrate-producing bacteria absent in other groups. The rural aerobiome provided significant protection against colitis across the majority of measured metrics. For the secondary outcome, no significant difference in colitis severity was observed between microbial exposure during infancy versus adulthood. Conclusion This study is the first to demonstrate that the aerobiome can modulate the mammalian colonic microbiome. Exposure to a soil-rich aerobiome representative of rural environments substantially ameliorated colitis severity in a murine model of UC, with data suggesting this effect is mediated by microbiome modification. These findings offer a plausible mechanism explaining geographical variation in UC incidence.