Identifying Candidates for Novel Customized Probiotics Targeting Obesity‐Related Vascular Dysfunction

Objectives The gut microbiota has emerged as a critical regulator of human health. Consequently, commercial probiotics have grown in popularity and become a multi‐billion dollar industry. However, existing data have questioned the efficacy of commercial probiotics in the treatment and prevention of chronic diseases. One possible reason for the limited efficacy is that commercial probiotics are formulated indiscriminately, without regard to the gut microbial deficiencies of the patients. A more effective approach may be to administer the specific bacterial species that are reduced in the patient population, and whose reduction correlates with the presence of disease. Therefore, the goal of this project was to identify potential bacterial species for the formulation of a novel customized probiotic for the treatment and prevention of obesity‐related vascular dysfunction. Methods In order to identify potential candidates for a customized probiotic, data were pooled from the following mice in five independent studies that examined the role of the gut microbiota in obesity‐related vascular dysfunction: 1) C57BL/6 male mice fed either a standard low‐fat or Western diet; 2) lean male C57BL/6 mice that received microbiota transplantation from other C57BL/6 mice or from genetically obese ( ob/ob ) mice; 3) male ob/ob mice that received microbiota transplantation from other ob/ob mice or from lean C57BL/6 mice; 4) male genetically obese, diabetic ( db/db ) mice; and 5) male and female germ free mice that received microbiota transplantation from either lean or obese human donors. All mice underwent measurement of microbiota composition, arterial stiffness (via pulse wave velocity), endothelial function (via endothelium‐dependent dilation of mesenteric arteries) and glucose tolerance (via ip glucose tolerance test), and relations between these outcomes and individual bacterial species were examined. Results In the pooled cohort, we found that the abundance of Akkermansia (p = 0.09) and Bifidobacterium (p = 0.015) were significantly reduced in obese mice (or mice treated with obese microbiota) compared to lean mice. Pulse wave velocity and glucose tolerance negatively correlated with both Akkermansia (r = − 0.438, p <0.0001; r = − 0.331, p = 0.0071) and Bifidobacterium (r = − 0.171, p = 0.170; r = − 0.207, p = 0.1068), respectively. Body weight negatively correlated with Bifidobacterium (r = −0.607, p < 0.0001). Both endothelial dependent dilation (r = 0.317, p = 0.0236), and endothelial independent dilation (r = 0.222, p = 0.129) positively correlated with Bifidobacterium but not with Akkermansia.Conclusions These data indicate that genetically‐ and diet‐induced obese mice display relative deficiencies of Akkermansia and Bifidobacterium which correlate with measures of metabolic and vascular dysfunction, suggesting that these bacterial species are potential candidates for a customized probiotic. Future studies will compare the efficacy of a commercial probiotic to a customized probiotic, specifically formulated to ameliorate these bacterial deficiencies, in preventing or reversing obesity‐related vascular dysfunction. Support or Funding Information NIH R01 HL14411; American Heart Association #18TPA34170585; NIFA AES COL00766