Neighborhood Environment Associates with Trimethylamine-N-Oxide (TMAO) as a Cardiovascular Risk Marker

Abstract

Background: Neighborhoods and the microbiome are linked to cardiovascular disease (CVD), yet investigations to identify microbiome-related factors at neighborhood levels have not been widely investigated. We sought to explore relationships between neighborhood deprivation index (NDI) and the microbial metabolite, trimethylamine-N-oxide. We hypothesized that inflammatory markers and dietary intake would be mediators of the relationship. Methods: African-American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross-sectional community-based study. US census-based neighborhood deprivation index (NDI) measures (at the census-tract level) were determined. Serum samples were analyzed for CVD risk factors, cytokines, and the microbial metabolite, trimethylamine-N-oxide (TMAO). Self-reported dietary intake based on food groups was collected. Results: Study participants (n = 60) were predominantly female (93.3%), with a mean (SD) age of 60.83 (+/−10.52) years. Mean (SD) NDI was −1.54 (2.94), and mean (SD) TMAO level was 4.99 (9.65) µmol/L. Adjusting for CVD risk factors and BMI, NDI was positively associated with TMAO (β = 0.31, p = 0.02). Using mediation analysis, the relationship between NDI and TMAO was significantly mediated by TNF-α (60.15%) and interleukin)-1 β (IL; 49.96%). When controlling for clustering within neighborhoods, the NDI-TMAO association was no longer significant (β = 5.11, p = 0.11). However, the association between NDI and IL-1 β (β = 0.04, p = 0.004) and TNF-α (β = 0.17, p = 0.003) remained. Neither NDI nor TMAO was significantly associated with daily dietary intake. Conclusion and Relevance: Among a small sample of African-American adults at risk for CVD, there was a significant positive relationship with NDI and TMAO mediated by inflammation. These hypothesis-generating results are initial and need to be confirmed in larger studies.

Social Determinants of Cardiovascular Disease

“… 142 In a recent study from our lab, we demonstrated that within a cohort of Black individuals, neighborhood deprivation index as a marker of neighborhood-level SES was associated with increased levels of TNF-α and IL-1β. 143 We also determined that neighborhood deprivation was associated with trimethylamine N-oxide, 143 a biomarker associated with the gut microbiome, cardiovascular risk factors, and CVD mortality. 144 Interestingly, our data showed that the neighborhood deprivation index-to-trimethylamine N-oxide relationship was significantly mediated by the TNF-α and IL-1β response, 143 suggesting a need for future work to examine how inflammation induced by adverse SDoH may relate to the gut microbiome and CVD risk.…”

“… 143 We also determined that neighborhood deprivation was associated with trimethylamine N-oxide, 143 a biomarker associated with the gut microbiome, cardiovascular risk factors, and CVD mortality. 144 Interestingly, our data showed that the neighborhood deprivation index-to-trimethylamine N-oxide relationship was significantly mediated by the TNF-α and IL-1β response, 143 suggesting a need for future work to examine how inflammation induced by adverse SDoH may relate to the gut microbiome and CVD risk. Ultimately, more work is needed to link neighborhood factors to inflammatory markers and immune cell function.…”

A metabolic readout of the urine metabolome of COVID-19 patients

“…The increased concentration of TMAO in the body has been associated with health problems such as inflammatory processes, risk of arteriosclerosis, neurological disorders, or kidney damage, among other diseases. However, the mechanism associated with these damages is still unknown (Barrea et al, 2018 ; Brial et al, 2018 ; Chhibber-Goel et al, 2017 ; Coras et al, 2019 ; Dove et al, 2012 ; Farmer et al, 2021 ; Gatarek & Kaluzna-Czaplinska, 2021 ; Janeiro et al, 2018 ; Koeth et al, 2013 ). One of the characteristics of COVID-19 is the appearance of inflammatory processes, which could be leading to increased levels of TMAO in the urine of COVID-19 patients, as occurs with other inflammatory processes (Tang et al, 2015 ; Yang et al, 2019 ).…”

By what molecular mechanisms do social determinants impact cardiometabolic risk?

“…Nazmi et al also reported that higher levels of safety are associated with decreased IL-6 levels even after adjustment for race, ethnicity, and SES [ 146 ]. In a recent study from our own laboratory, we demonstrated that within a cohort of African Americans, neighborhood socioeconomic deprivation as measured by a neighborhood deprivation index (NDI) was associated with increased levels of TNFα and IL-1β [ 147 ]. We also determined that neighborhood deprivation was positively associated with TMAO [ 147 ], a biomarker associated with the microbiome, CV risk factors, and CVD mortality [ 148 , 149 ].…”

“…In a recent study from our own laboratory, we demonstrated that within a cohort of African Americans, neighborhood socioeconomic deprivation as measured by a neighborhood deprivation index (NDI) was associated with increased levels of TNFα and IL-1β [ 147 ]. We also determined that neighborhood deprivation was positively associated with TMAO [ 147 ], a biomarker associated with the microbiome, CV risk factors, and CVD mortality [ 148 , 149 ]. Interestingly, our data show that the NDI-to-TMAO relationship was significantly mediated by the TNFα and IL-1β [ 147 ], indicating the overall significant role of systemic low-grade inflammation in potentially accelerating CVD through multiple mechanisms, including effects related to the microbiome [ 150 ].…”