Excessive iron intake is detrimental to human health, especially to the liver, which is the main organ for iron storage. Excessive iron intake can lead to liver injury. The gut-liver axis (GLA) refers to the bidirectional relationship between the gut and its microbiota and the liver, which is a combination of signals generated by dietary, genetic and environmental factors. Excessive iron intake disrupts the GLA at multiple interconnected levels, including the gut microbiota, gut barrier function, and the liver's innate immune system. Excessive iron intake induces gut microbiota dysbiosis, destroys gut barriers, promotes liver exposure to gut microbiota and its derived metabolites, and increases the pro-inflammatory environment of the liver. There is increasing evidence that excess iron intake alters the levels of gut microbiota-derived metabolites such as secondary bile acids (BAs), short-chain fatty acids, indoles, and trimethylamine N-oxide, which play an important role in maintaining homeostasis of the GLA. In addition to iron chelators, antioxidants, and anti-inflammatory agents currently used in iron overload therapy, gut barrier intervention may be a potential target for iron overload therapy. In this paper, we review the relationship between excess iron intake and chronic liver diseases, the regulation of iron homeostasis by the GLA, and focus on the effects of excess iron intake on the GLA. It has been suggested that probiotics, fecal microbiota transfer, farnesoid X receptor agonists, and microRNA may be potential therapeutic targets for iron overload-induced liver injury by protecting gut barrier function.

Due to high mortality rates and poor prognosis, liver injury remains one of the leading causes of mortality worldwide. Amounting evidence suggested that the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome, which promotes pro-interleukin-1β (pro-IL-1β) and pro-interleukin-18 (pro-IL-18) cleavage and maturation play a vital role in the occurrence and development of liver injury and liver disease. Mitochondrial dysfunction is a common co-occurring event in liver injury. Abnormal mitochondrial function has also been shown to be closely related to NLRP3 inflammasome activation. Currently, natural products have attracted the attention of researchers as potential therapeutic agents for liver injury and liver disease due to their less toxicity and multi-targeting advantages. A number of natural products have been discovered to prevent and treat liver injury by modulating the activation of NLRP3 inflammasome. In this review, we highlight the mechanisms involved in the regulation of NLRP3 inflammasome activation by mitochondria during liver injury and natural products that target mitochondrial function processes to prevent or treat liver injury. Our paper may shed insight into novel viewpoint and target for prevention and treatment of liver injury based on NLRP3 inflammasome.

Arsenic (As) is a toxic metalloid exist ubiquitously in environment. Epidemiological studies and laboratory animal studies have verified that As damages multiple organs or tissues in the body and is associated with a variety of diseases. Changes in metabolites usually indicate disturbances in metabolic pathways and specific metabolites are considered as biomarkers of diseases or drugs/toxins or environmental effects. Metabolomics is the quantitative measurement of the dynamic multi-parameter metabolic responses of biological systems due to pathophysiological or genetic changes. Current years, some metabolomic studies on the hazardous effect of environmental As on humans have been reported. In this paper, we first overviewed the metabolomics studies of environmental As exposure in humans since 2011, emphasizing on the data mining process of metabolic characteristics related to the hazardous effects of environmental As on humans. Then, the relationship between metabolic characteristics and the toxic mechanism of environmental As exposure in humans were discussed, and finally, the prospects of metabolomics studies on populations exposed to environmental As were put forward. Our paper may shed light on the study of mechanisms, prevention and individualized treatment of As poisoning.

Purpose: Gastrointestinal heat retention syndrome (GHRS) often occurs in adolescents, resulting into nervous system injury. Realgar, an arsenic mineral with neuroprotective effect, has been widely used to treat GHRS. However, its mechanism of action remains unknown. Methods: A GHRS rat model was established using a high protein and high calorie diet. We performed macroscopic characterization by assessing bowel sounds, hot/cold preference, anal temperature, and fecal features. Atomic fluorescence spectroscopy was employed to evaluate brain arsenic level while hippocampal ultrastructural changes were analyzed using transmission electron microscopy. In addition, inflammatory cytokines and BBB breakdown were analyzed by western blotting, immunofluorescence assays, and immunohistochemistry staining. We also evaluated hippocampal metabolites by LC-MS while fecal microorganisms were assessed by 16S rDNA sequencing. Results: Our data showed that the high protein and high calorie diet induced GHRS. The rat model depicted decreased bowel sounds, increased fecal characteristics score, preference for low temperature zone, and increased anal temperature. In addition, there was increase in inflammatory factors IL-6, Iba-1, and NF-κB p65 as well as reduced BBB structural protein Claudin-5 and Occludin. The data also showed appearance of hippocampus metabolites disorder and fecal microbial imbalance. Realgar treatment conferred a neuroprotective effect by inhibiting GHRS-specific characteristics, neuroinflammatory response, BBB impairment, metabolites disorder, and microbial imbalance in the GHRS rat model. Conclusion: Taken together, our analysis demonstrated that realgar confers a neuroprotective effect in GHRS rats through modulation of the microbiota-gut-brain axis.