The WARRIOR project serves as a model for population-based microbiome research and findings will provide important insights into human variability and the role of the microbiome in protection or exacerbation of the global MDRO crisis.
At a Glance
Antibiotic resistance makes drugs less effective at treating infections, which can be very dangerous. This study explored the role that dietary fiber intake and the diversity of microorganisms in the gut may play in reducing the risk of colonization by multidrug resistant organisms (MDROs).
The study found higher rates of MDRO colonization in older, low-income, and urban-living individuals and that increased dietary fiber intake may be associated with slightly lower rates of MDRO gut colonization. Further study using leveraged grant funding in underway.
The Challenge
Preventing infection by MDROs is crucial. The infections caused by antibiotic resistant bacteria are often serious and can be life-threatening, and treatment options are decreasing. MDRO transmission has traditionally been associated with healthcare settings, where it can threaten patients, but is also occurring more often in community settings. Dietary fiber increases gut microbial diversity, which may help prevent colonization and infection by MDROs through competition and increased immune function.
Microorganisms also play a role in other biological mechanisms, and imbalances can lead to a variety of negative health impacts. Understanding the vulnerability of different communities and the role of the gut microbiome in preventing antibiotic resistance is therefore important, but the work requires large sample sizes, participants willing to provide stool and other samples and complete surveys, and extensive lab work.
Project Goals
The primary goal of the WARRIOR project has been understanding the relationship between the amount of fiber in the diet and the type of bacteria present in the gut, including antibiotic resistant bacteria (MDROs). A secondary purpose of the study is to create a biorepository of multiple body site specimens (including stool, nasal, oral, and skin swabs) for future microbiota research. The samples collected for the WARRIOR project were also used for an ancillary study of the relationship between lead exposure and antibiotic resistance.
The PIs identified three primary goals, condensed and paraphrased here:
Determine how fiber intake (including fiber type) relates to the diversity of gut microbiota in Wisconsin residents.
Determine how fiber intake (including fiber type) relates to MDRO populations in different groups of Wisconsin residents.
Identify clusters of foods associated with high microbial diversity and low MDRO
colonization in representative groups.
The researchers and their collaborators had a goal of collecting stool samples as well as nasal, oral, and skin swabs from 600 participants as an ancillary study of the Survey of the Health of Wisconsin (SHOW). Participants were to be recruited from Waushara, Milwaukee, Eau Claire and Brown Counties.
Results
Four grants (one from the National Institutes of Health and three from internal funding agencies) proposing further use of WARRIOR data and biological specimens have been funded. Two further grants are proposed, and multiple conference presentations as well as two publications have been completed, with another in progress.
•Aim 1: The grantees succeeded in collecting a large amount of data from more than 600 participants (the original target sample). The total number of participants with viable stool samples and dietary fiber consumption data from the questionnaires was 671; however, incomplete observations were omitted from analyses, resulting in an analytical sample size of 566.
Aim 2: Among 671 participants available for this aim, 22.7% tested positive for stool colonization by an MDRO. 22 participants tested positive for toxigenic C. difficile and 3 tested positive for non-toxigenic C. difficile. Mean dietary fiber was 19.6 g for negative participants and 21.4 ?g/L for positive participants.
Aim 3: Results are pending, and will be published in a publication that is in preparation.
MDRO colonization was most prevalent in those age 70+, females, those with income <200% of the Federal Poverty Limit (FPL), and those that live in an urban area.
Ancillary studies on the relationship between lead exposure and MDRO colonization and gut microbiome diversity were also conducted. Using urine samples from the Wisconsin Partnership Program-funded Survey of the Health of Wisconsin, the team found that:
Lead exposure is likely associated with gut colonization by antibiotic resistant bacteria. The probability of MDRO colonization was 2.5 times higher for those in the highest quartile of urinary lead.
Results from the gut microbiome diversity study also suggest that lead exposure is associated with differences in the composition of the adult gut microbiota.
Lasting Impact
The WARRIOR project sets an important baseline for understanding the relationships between fiber intake and lead exposure to MDRO colonization in the adult gut microbiome in a community health context.
• The results suggest a slight beneficial relationship between dietary fiber intake and MDRO colonization, although further analysis with more varied fiber exposure is called for. If further studies confirm that more fiber leads to lower rates of MDRO colonization, doctors could prescribe high-fiber diets to those at risk of infection (see Learn More).
• Old age, gender, low income status, and urbanicity were associated with MDRO colonization, while hypothesized risk factors for colonization, such as recent use of antibiotics, hospital and farm exposure were not significantly associated with fiber consumption and MDRO colonization. In the lead study, similar factors as well as race were associated with MDRO colonization. Thus, the studies have health equity implications since race, socioeconomic status and geography play a role in individual susceptibility to MDRO colonization.
• Finally, the biorepository developed as part of this study will enable future studies to follow up on the progress made in the WARRIOR study, ensuring a return on the Partnership Program’s investment in faculty and staff time, lab work, and participant recruitment.
Additionally, Dr. Safdar has leveraged a five-year National Institute of Allergy and Infectious Disease (PI: Andes), with an annual budget over $700,000, that uses the WARRIOR project biological samples to test whether bioactive molecules can produce antibiotics without disrupting the host microbiome.
