Diesel exhaust particle inhalation in conjunction with high-fat diet consumption alters the expression of pulmonary SARS-COV-2 infection pathways, which is mitigated by probiotic treatment in C57BL/6 male mice.

Abstract

Background: Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet.

Methods: Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic^® Barrier probiotics in their drinking water throughout the study.

Results: Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment.

Conclusion: These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.