Research Article: The human microbiota is associated with cardiometabolic risk across the epidemiologic transition

Date Published: July 24, 2019

Publisher: Public Library of Science

Author(s): Na Fei, Beatriz Peñalver Bernabé, Louise Lie, Danny Baghdan, Kweku Bedu-Addo, Jacob Plange-Rhule, Terrence E. Forrester, Estelle V. Lambert, Pascal Bovet, Neil Gottel, Walter Riesen, Wolfgang Korte, Amy Luke, Stephanie A. Kliethermes, Brian T. Layden, Jack A. Gilbert, Lara R. Dugas, Juan J. Loor.


Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25–45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Partial Text

Metabolic syndrome and cardiometabolic (CM) risk are associated with increased morbidity and mortality[1–3], and includes five risk factors: visceral obesity, elevated fasted blood glucose and elevated blood pressure, decreased high density lipoprotein (HDL) cholesterol, hypertriglyceridemia [4]. In the US, as many as 35% of all US adults present with CM risk [5], when defined using the “Adult Treatment Panel criteria”[6]. Between 1988 and 2012, the greatest increase in the prevalence of CM disease was seen among black men, estimated to be currently around 55%, and rose by 41% among black women [5]. There is increasing evidence that the composition and metabolic function of the gut microbiota correlate with the progression and pathogenesis of CM disease, although the causality remains unclear [7].

In our study of African-origin adults from Ghana, South Africa, Jamaica and the US, we performed a comprehensive analysis exploring the relationship between the gut and oral microbiota and elevated CM risk, representing 4 geographically diverse countries spanning an epidemiologic transition. Overall, our results provide evidence that the gut and oral microbiota may potentially be both predictive as well as a therapeutic target for elevated CM risk, and is in line with previous evidence that the human microbiota are associated with CM risk [54, 55].

In conclusion, our findings extend our insights into the relationship between the human microbiota and elevated CM risk at the structural and functional level, pointing to possible future therapeutic modalities for CM risk targeting the gut and oral microbiota. Our findings identify previously unknown links between gut and oral microbiota alterations, and CM risk, suggesting that gut and oral microbial composition, structure and predicted functional potential may serve as predictive biomarkers for identifying CM risk, as well as therapeutic targets. The features of association between human microbiome and CM risk is diverse in different populations and indicates that different interventions and potential individualized treatment methods targeting the microbiome need to be developed to control the development of CM risk across the world. Indeed, we are continuing our exploration of these relationships in our large international cohort of African-origin adults spanning the epidemiologic transition [37].




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