Cervical cancer remains one of the most prevalent cancers among females worldwide. Therefore, it is important to discover new biomarkers for early diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer, preferably non-invasive ones. In the present study, we aimed to identify unique metabolic signatures for CINs and cervical cancers using global and targeted metabolomic profiling. Plasma samples (69 normal, 55 CIN1, 42 CIN2/3, and 60 cervical cancer) were examined by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with multivariate statistical analysis. Metabolic pathways were analyzed using the integrated web-based tool MetaboAnalyst. A multivariate logistic regression analysis was conducted to evaluate the combined association of metabolites and human papillomavirus (HPV) status with the risk of cervical carcinogenesis. A total of 28 metabolites exhibiting discriminating levels among normal, CIN, and cervical cancer patients (Kruskal–Wallis test p < 0.05) were identified in the global profiling analysis. The pathway analysis showed significantly altered alanine, aspartate, and glutamate metabolic pathways (FDR p-value < 0.05) in both the discovery and validation phases. Seven metabolites (AMP, aspartate, glutamate, hypoxanthine, lactate, proline, and pyroglutamate) were discriminated between CINs and cervical cancer versus normal (area under the curve (AUC) value > 0.8). The levels of these metabolites were significantly high in patients versus normal (p < 0.0001) and were associated with increased risk of developing CIN2/3 and cervical cancer. Additionally, elevated levels of the seven metabolites combined with positive HPV status were correlated with substantial risk of cancer progression. These results demonstrated that metabolomics profiling is capable of distinguishing CINs and cervical cancers from normal and highlighted potential biomarkers for the early detection of cervical carcinogenesis.

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category ‘Defense mechanisms’ was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations.

Recently, diets with higher inflammatory potentials based on the dietary inflammatory index (DII^®) have been shown to be associated with increased cardiovascular disease (CVD) risk in the general population. We aimed to prospectively investigate the association between the DII and CVD risk in the large Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort comprised of 162,773 participants (men 55,070; women 107,703). A validated semi-quantitative food frequency questionnaire (SQ-FFQ) was used to calculate the DII score. Statistical analyses were performed by using a multivariable Cox proportional hazard model. During the mean follow-up of 7.4 years, 1111 cases of CVD were diagnosed. Higher DII score was associated with increased risk of CVD in men (hazard ratio [HR]_{Quintile 5 vs. 1} 1.43; 95% CI 1.04–1.96) and in women (HR_{Quintile 5 vs. 1} 1.19; 95% CI 0.85–1.67), although not significant for women. The risk of CVD was significantly higher in physically inactive men (HR_{Quintile 5 vs. 1} 1.80; 95% CI 1.03–3.12), obese men (HR_{Quintile 5 vs. 1} 1.77; 95% CI 1.13–2.76) and men who smoked (HR_{Quintile 5 vs. 1} 1.60; 95% CI 1.10–2.33), respectively. The risk of developing stroke was significantly higher for men (HR_{Quintile 5 vs. 1} 2.06; 95% CI 1.07–3.98; p = 0.003), but not for women. A pro-inflammatory diet, as indicated by higher DII scores, was associated with increased risk of CVD and stroke among men.

Previous studies have found that diet’s inflammatory potential is related to various diseases. However, little is known about its relationship with osteoporosis. The aim of this study was to investigate the association between the dietary inflammatory index (DII^®) and osteoporosis risk in a large-scale prospective cohort study in Korea. This prospective cohort study included 159,846 participants (men 57,740; women 102,106) from South Korea with a mean follow-up of 7.9 years. The DII was calculated through a validated semi-quantitative FFQ (SQFFQ), and information on osteoporosis was self-reported by the participants. Analyses were performed by using a multivariable Cox proportional hazard model. Higher DII scores were associated with higher osteoporosis risk (HR 1.33; 95% CI 1.12–1.58). In women, a higher DII score indicated a higher risk of osteoporosis (HR 1.33; 95% CI 1.11–1.59). However, a hazards ratio of similar magnitude in men was not significant (HR 1.32; 95% CI 0.64–2.71). Post-menopausal women had higher risks of osteoporosis for higher DII scores (HR 1.33; 95% CI 1.09–1.63), whereas among pre-menopausal women, the relationship was not statistically significant (HR 1.39; 95% CI 0.87–2.21). Also, there was an increase in osteoporosis risk when the DII increased among women participants with irregular physical activity (HR 1.53; 95% CI 1.17–2.01); however, there was no statistically significant increase in osteoporosis risk among women participants with regular physical activity (HR 1.19; 95% CI 0.93–1.52). A more pro-inflammatory diet was significantly associated with higher osteoporosis risk in women. Given the similar magnitude of the hazards ratio, studies with sufficient numbers of men are warranted.

In previous studies, the elevated dietary inflammatory index (DII^®) scores have been consistently associated with several chronic diseases. However, the relationship with hyperuricemia remains unknown. The aim of this study was to determine if the DII is associated with hyperuricemia risk. The study included 13,701 participants (men 5102; women 8599) in a large-scale cross-sectional study in South Korea. A validated semi-quantitative food frequency questionnaire (SQFFQ) was used to measure dietary intake, and blood samples were obtained to determine hyperuricemia. As the DII score increased, the hyperuricemia risk increased among women (OR 1.35, 95% CI 1.03–1.77, p trend = 0.02). However, no significant results were found for men. Women with lower BMI scores had higher risks of hyperuricemia with higher DII scores (OR 1.62, 95% CI 1.05–2.52, p trend = 0.03). As the DII increased, however, only women who consumed alcohol (“past or current drinkers”) had higher risks of hyperuricemia (OR 1.92, 1.22–3.02, p trend = 0.004). Among the DII components, intake of flavonoids showed a significant association with the hyperuricemia risk in women (OR 0.75, 0.59–0.96, p trend = 0.03). Our results suggest that higher intake of pro-inflammatory diet is significantly associated with higher risk of hyperuricemia among women. These results reinforce the importance of less pro-inflammatory habitual dietary patterns in lowering the risk of hyperuricemia and secondary afflictions such as cardiovascular diseases.

Mercury is a cumulative neurotoxic agent, exposure to high levels of which may increase the risk of psychiatric symptoms. The purpose of this study was to examine the associations between blood mercury and depression risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) with 11,754 participants (male: 5834 female: 5920) aged ≥19 years from 2008 to 2013. The associations of blood mercury with risk of depression were estimated using multivariate logistic regression after adjustment for potential confounders. We found a significantly increased risk of depression in the highest quintile for blood mercury (multivariate OR = 2.05; 95% CI = 1.20–3.48; p trend = 0.03) among female, but not male. A stratification analysis by fish intake showed that the association between depression and blood mercury was strengthened (OR = 4.00; 95% CI = 1.51–10.6; p trend = 0.015) among females with the lowest tertile of fish intake. The results of this study suggest that higher levels of blood mercury, especially in cases of lower fish intake, are positively associated with the risk of depression in Korean women.