The overuse of antibiotics has propelled the spread of antibiotic resistance and inflammatory disorders. Despite this, many people expose their skin to a potent antimicrobial on a near daily basis. This antimicrobial, the metal aluminum, is the active ingredient in antiperspirants. Seemingly innocuous, antiperspirants induce severe ecological shifts (dysbiosis) in the skin microbiome, the communities of microbes that reside on skin. Through repeated exposure, antiperspirants may also cause these communities to develop resistance to aluminum, a possibility of high concern since metal and antibiotic resistance are often linked. As commensals, skin microbes cooperate with the immune system to thwart invading pathogens and suppress inflammation. However, dysbiosis can lead these communities to become pro-inflammatory such as in eczema, and in the context of skin injury, self-contamination with commensals can lead to antibiotic-resistant infections such as chronic wounds. How antiperspirants influence these disease functions of skin commensals is unknown. This proposal?s central hypothesis is that aluminum drives antibiotic resistance and pro-inflammatory dysbiosis in the skin microbiome. Recently, metabolic products (metabolites) have been recognized as strong modulators of microbial virulence and host inflammation, suggesting therapeutic applications. Thus, different aspects of the hypothesis will be addressed as follows: (1) determine how aluminum selects for antibiotic resistance in skin commensals, (2) discover metabolites for treating wounds infected with aluminum-resistant skin commensals, (3) discover metabolites for treating aluminum-induced dysbiosis, inflammation, and pathogen invasion. This proposal may reveal how a routinely used antimicrobial product contributes to skin inflammation and the spread of antibiotic resistance.

Public Health Relevance

Antiperspirants are regularly used by millions of people, but the consequences of its active ingredient aluminum, a potent antimicrobial, have not been fully explored. Prior studies have shown that aluminum can select for antibiotic resistance and disturb the ecology skin microbial communities, potentially leading to inflammation. The goal of this proposal is to determine the contribution of aluminum to the emergence of antibiotic resistance and pro-inflammatory microbial communities in the skin microbiome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Project #
1FI2GM128736-01
Application #
9574904
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Gibbs, Kenneth D
Project Start
2018-09-01
Project End
2021-08-31
Budget Start
2018-09-01
Budget End
2021-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
U.S. National Institute Allergy & Infect Dis
Department
Type
DUNS #
085637655
City
Bethesda
State
MD
Country
United States
Zip Code
20892