Microbiota and the nitrogen cycle: Implications in the development and progression of CVD and CKD

• NO is produced via the nitrogen cycle, through the reduction of nitrate to nitrite.
• The reduction process mainly occurs in the mouth by commensal microbiota.
• Ammonia or urea can build up leading to disease development.
• Altering the GIT nitrate or nitrite can have an impact on bacterial growth.
• There is a need for therapeutic interventions that will reduce CKD and CVD.

Chronic kidney disease (CKD) is associated with an increased risk of death from cardiovascular disease (CVD). One factor involved in CVD development is nitric oxide (NO), which acts as a powerful vasodilator. NO is produced via the nitrogen cycle, through the reduction of nitrate to nitrite with the process mainly occurring in the mouth by commensal microbiota. People with CKD have compromised microbiota (dysbiosis) with an increased abundance of potentially pathogenic and pro-inflammatory bacteria capable of producing uremic toxins that contribute to CKD development and reduce enzymatic NO production. However, to date, few studies have comprehensively documented the gut or saliva microbiota in the CKD population or investigated the role of NO in people with CKD. This review will discuss NO pathways that are linked to the progression of CKD and CVD and therapeutic options for targeting these pathways.