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Perfluorooctanoic acid (PFOA), an environmental pollutant, is widely engaged in industrial products and tends to accumulate in the liver. Emerging evidence has suggested that the gut microbiome is a pivotal player in maintaining animal health and can potentially altered by xenobiotic. However, few studies explored whether PFOA-induced liver injury is associated with gut microbiota dysbiosis. In the present study, the effects of subacute and subchronic PFOA exposure on liver and gut microbiota in C57BL/6J mice were investigated. Our findings showed that both subacute and subchronic exposure to PFOA induced the liver inflammation, disrupted antioxidative homeostasis and caused liver histological abnormalities with detectable hepatomegaly, ultimately triggering liver injury. Besides, 16S rRNA sequencing analysis revealed that subacute PFOA exposure caused significant changes in the abundances of intestinal flora known to contribute to liver inflammation and oxidative stress, such as the Dehalobacterium and Bacteroides genera. Exposure to subchronic toxicity mainly induced the decrease in commensal probiotics including Lactobacillus and Bifidobacterium genera, which are potentially beneficial to liver damage, compared with that in the untreated group. They also resulted in disturbed functional capabilities of the microbial communities by a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Additionally, the levels of short-chain fatty acids (SCFAs), especially butyric acid, were significantly reduced by PFOA administration. Collectively, our observations suggested that liver damage induced by both subacute and subchronic PFOA exposures probably partly related to the gut microbiota dysbiosis and provided a new insight into the role of PFOA in liver injury.

Xiaodan Li,1 Rong Chen,2 Zhifa Li,2 Bing Luo,1 Wenyan Geng,1 Xiaobing Wu2 1Clinical Laboratory, The Third Affiliated Hospital of the Guangzhou Medical University, Guangzhou 510150, People’s Republic of China; 2Gastrointestinal Surgery, The Third Affiliated Hospital of the Guangzhou Medical University, Guangzhou 510150, People’s Republic of ChinaCorrespondence: Xiaobing WuGastrointestinal Surgery, The Third Affiliated Hospital of the Guangzhou Medical University, NO. 63, Duobao Road, Liwan District, Guangzhou City, Guangdong Prov 510150, People’s Republic of ChinaTel +8613544395215Fax +02081292182Email wuxiaobing270@126.comIntroduction: Colorectal cancer (CRC) is one of the most common illnesses that seriously threatens human health; many papers have reported that microRNAs (miRNAs) are promising biomarkers for cancer detection. However, miRNAs have not been used in clinical practice even though they are superior to the currently used screening tools, such as the fecal occult blood test (FOBT) and carcinoembryonic antigen (CEA) measurement.Methods: In this study, we focused on the usefulness of a panel of miRNAs and the combination of miRNAs with the FOBT and CEA measurement, the currently used general diagnosis methods, to improve the accuracy of CRC diagnosis.Results: The results showed that the miRNA panel has great potential value as a diagnostic biomarker with high specificity and sensitivity, and further analysis demonstrated that the miRNA panel had higher sensitivity and specificity than the FOBT and CEA measurement, even when these methods were combined. More importantly, although the miRNA panel is superior to the FOBT and CEA measurement, it cannot replace them.Conclusions: In this research, we investigated whether complementarity exists between the miRNA panel and the FOBT and CEA measurement for CRC diagnosis. Interestingly, the results indicated that the FOBT and CEA measurement could improve the positivity rate of the miRNA panel as a biomarker and vice versa.Keywords: microRNAs, colorectal cancer, biomarker