Could targeting the gut microbiome provide a novel treatment option for intermittent claudication.

Peripheral artery disease is a highly prevalent, age-related inflammatory condition. Many patients are asymptomatic, while others progress to chronic limb-threatening ischemia associated with high rates of morbidity and mortality. In between this wide spectrum of disease severity, patients often present with intermittent claudication which can be debilitating and lifestyle-limiting. Targeting the gut microbiome may be a novel strategy to treat patients with claudication, primarily through dietary interventions that promote restoration of microbial homeostasis. A review of the literature suggests that gut dysbiosis, circadian dysrhythmia, and vascular senescence are key interacting contributors to claudication, and each of these factors are amenable to modulation. These may include introducing key SCFA-producing bacteria (e.g. butyrate and propionate) or specific bacterial species that are associated with vigorous exercise in athletic individuals (e.g. Veillonella atypica and Prevotella), natural dietary senolytics (e.g. o-Vanillin), and behavioural changes such as time restricted eating, intermittent fasting and calorie restriction. Furthermore, resistance training provides an important exercise option in this cohort without additional strain on the lower limbs. We propose that an integrated cocktail of selective dietary interventions to restore gut homeostasis, tailored resistance exercise regimes, and entrainment to normalized circadian rhythm will provide a significant beneficial impact on exercise capacity in patients with claudication.