Obesity is the main driver of altered gut microbiome functions in the metabolically unhealthy

ABSTRACT

Obesity (OB) and cardiometabolic disease are major public health issues linked to changes in the gut microbiome. OB and poor cardiometabolic health status (CHS) are often comorbid, which hinders efforts to identify components of the microbiome uniquely linked to either one. Here, we used a deeply phenotyped cohort of 408 adults from Colombia, including subjects with OB, unhealthy CHS, or both, to validate previously reported features of gut microbiome function and diversity independently correlated with OB or CHS using fecal metagenomes. OB was defined by body mass index, waist circumference, and body fat; CHS as healthy or unhealthy according to blood biochemistry and anthropometric data. We found that OB, more so than metabolic status, drove associations with gut microbiome structure and functions. The microbiome of obese individuals with and without co-existing unhealthy CHS was characterized by reduced metagenomic diversity, reduced fermentative potential and elevated capacity to respond to oxidative stress and produce bacterial antigens. Disease-linked features were correlated with increased host blood pressure and inflammatory markers, and were mainly contributed by members of the family Enterobacteriaceae. Our results link OB with a microbiome able to tolerate an inflammatory and oxygenated gut state, and suggest that OB is the main driver of microbiome functional differences when poor CHS is a comorbidity.

KEYWORDS:

• Obesity
• cardiometabolic disease
• gut microbiome
• fecal metagenomes
• functional potential
• microbiome diversity

Acknowledgments

We thank the participants who took part in the study, and the Vidarium, EPS SURA and Dinámica IPS staff that helped with recruitment and field work. Some authors of this work collaborate through the Microbiome & Health Network. We are grateful to Alejandra Duque, Albane Ruaud, Taichi Suzuki, William Walters and Laura Salazar-Jaramillo for the fruitful discussions and comments.

Disclosure statement

While engaged in this project, J.S.E. was employed by a research centre that belongs to a food company (Grupo Empresarial Nutresa). J.d.l.C-Z., K.H., N.D.Y. and R.E.L. report no conflict of interest.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2246634

Additional information

Funding

This work was supported by the Max Planck Society (J.d.l.C-Z., K.H., N.D.Y., R.E.L.) and Vidarium–Nutrition, Health and Wellness Research Center (J.S.E.).