Gut microbiota has been studied in relation to human health and disease prediction for decades. Also, immune checkpoints (ICPs) are enthusiastically investigated for anti-tumor immunotherapy. Recent studies show potential of gut microbiome and gut cytokines as biomarkers for carcinogenesis and response prediction of immune checkpoint inhibitor (ICI) response. Evidence has revealed that intestinal microorganisms play a major role in the effectiveness of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade. In this review, we have focused on how microbiome and microbiome-generated cytokines affect immune checkpoints. We have also described the molecular mechanisms behind this interplay and the bacterial strains that have a potential role in immunotherapy.

Remarkable progress has occurred over the past two decades in identifying microbiomes affecting the human body in numerous ways. The microbiome is linked to gastrointestinal (GI) tract cancer. The purpose of this study was to determine if there is a common microbiome among GI tract cancers and how the microbiome affects the disease. To ensure ethnic consistency, Korean patients with GI tract cancer were selected. Fusobacterium nucleatum is an enriched bacteria in all cancer tissues. F. nucleatum is a Gram-negative obligate anaerobe that promotes colorectal cancer. Through Gene Set Enrichment Analysis (GSEA) and Differentially Expressed Genes (DEG) analyses, the upregulation of the G2M checkpoint pathway was identified in the F. nucleatum-high group. Cell viability and G2M checkpoint pathway genes were examined in MC 38 cells treated with F. nucleatum. F. nucleatum upregulated the expression of G2M checkpoint pathway genes and the cell proliferation of MC 38 cells. F. nucleatum facilitated cancer’s use of G2M checkpoint pathways and F. nucleatum could be a therapeutic target in Korean GI tract cancer.

Disruption of the skin microbial balance can exacerbate certain skin diseases and affect prognosis and treatment. Changes in the distribution and prevalence of certain microbial species on the skin, such as Staphylococcus aureus (SA), can impact the development of severe atopic dermatitis (AD) or psoriasis (Pso). A dysfunctional skin barrier develops in AD and Pso due to SA colonization, resulting in keratinization and chronic or progressive chronic inflammation. Disruption of the skin barrier following SA colonization can elevate the production of T helper 2 (Th2)-derived cytokines, which can cause an imbalance in Th1, Th2, and Th17 cells. This study examined the ability of potential therapeutic skin microbiomes, such as Cutibacterium avidum R-CH3 and Staphylococcus hominis R9, to inhibit SA biofilm formation and restore skin barrier function-related genes through the activation of the aryl hydrocarbon receptor (AhR) and the nuclear factor erythroid-2-related factor 2 (Nrf2) downstream target. We observed that IL-4/IL-13-induced downregulation of FLG, LOR, and IVL induced by SA colonization could be reversed by dual AhR/Nrf2 activation. Further, OVOL1 expression may be modulated by functional microbiomes via dual AhR/Nrf2 activation. Our results suggest that our potential therapeutic skin microbiomes can prevent SA-derived Th2-biased skin barrier disruption via IL-13 and IL-4-dependent FLG deregulation, STAT3 activation, and AhR-mediated STAT6 expression.

The skin supports a diverse microbiome whose imbalance is related to skin inflammation and diseases. Exposure to fine particulate matter (PM2.5), a major air pollutant, can adversely affect the skin microbiota equilibrium. In this study, the effect and mechanism of PM2.5 exposure in HaCaT keratinocytes were investigated. PM2.5 stimulated the aryl hydrocarbon receptor (AhR) to produce reactive oxygen species (ROS) in HaCaT cells, leading to mitochondrial dysfunction and intrinsic mitochondrial apoptosis. We observed that the culture medium derived from a particular skin microbe, Staphylococcus epidermidis WF2R11, remarkably reduced oxidative stress in HaCaT cells caused by PM2.5-mediated activation of the AhR pathway. Staphylococcus epidermidis WF2R11 also exhibited inhibition of ROS-induced inflammatory cytokine secretion. Herein, we demonstrated that S. epidermidis WF2R11 could act as a suppressor of AhRs, affect cell proliferation, and inhibit apoptosis. Our results highlight the importance of the clinical application of skin microbiome interventions in the treatment of inflammatory skin diseases.

Obstructive acute pyelonephritis (OAPN) is a common condition that can rapidly become life-threatening. In particular, OAPN associated with ureteral stones (OAPN-US) should be treated by a diversion of the urinary tract. Notably, we focused on predicting septic shock, which can be highly fatal. Previous studies have suggested multiple variables for predicting septic shock, but most studies used the Sepsis-2 criteria, which were revised to the Sepsis-3 criteria in 2016. Furthermore, no studies have identified a confirmatory variable or proposed combination of multiple variables for the prediction of septic shock. This study aimed to determine the best combination of potential predictors of septic shock in patients with OAPN-US based on the Sepsis-3 criteria. Our approach was based on machine learning (ML) because previous studies have demonstrated high performance of ML and because it can easily identify the combined effects of multiple variables. We selected three variables from approximately 30 factors and compared five ML algorithms. Notably, the random forest algorithm demonstrated the best performance, with an area under the receiver operating curve of 0.9965 and accuracy of 0.9583. Among the selected factors, procalcitonin had the highest Gini importance score. To the best of our knowledge, this is the first study to use ML for the predication of septic shock. Excellent predictions were made after identifying the optimal combination of multiple predictors.