Abstract

Simple SummaryWhile modulating gut microbiota using dietary intervention with natural nutrients has proven to be effective in improving the response rate of immune checkpoint inhibitors (ICIs), the underpinning mechanism is poorly understood. This work demonstrates that the oral administration of ultrafine jujube powder (JP) let to a significant alteration of gut microbiota, an increased abundance of Clostridiales, including Ruminococcaceae and Lachnospiraceae, an elevated SCFA production, an intensified infiltration of CD8+T cells to the tumor microenvironment, and a greatly improved response of anti-PD-L1 treatment against murine colon adenocarcinoma. Moreover, the size of the JP particles had a significant impact on the abovementioned attributes. The present study demonstrates that dietary intervention with nutrients is highly effective in modulating the gut microbiota for an improved immune checkpoint blockage therapy.AbstractWhereas dietary intervention with natural nutrients plays an important role in activating the immune response and holds unprecedented application potential, the underpinning mechanism is poorly understood. The present work was dedicated to comprehensively examine the effects of ultrafine jujube powder (JP) on the gut microbiota and, consequentially, the effects associated with the response rate to anti-PD-L1 treatment against murine colon adenocarcinoma. A murine colon adenocarcinoma model with anti-PD-L1 immunotherapy was established to evaluate how dietary interventions affect the microbiota. In vitro and in vivo experiments confirmed the role of SCFAs in the immune response. Oral administration of JP greatly improves the response of anti-PD-L1 treatment against murine colon adenocarcinoma. Such an improvement is associated with the alteration of gut microbiota which leads to an increased abundance of Clostridiales, including Ruminococcaceae and Lachnospiraceae, an elevated SCFA production, and an intensified infiltration of CD8+T cells