Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

Curcumin has antioxidant functions, regulates the intestinal microbial composition, and alleviates mycotoxin toxicity. The present study aimed to explore whether curcumin could alleviate ochratoxin A (OTA)-induced liver injury via the intestinal microbiota. A total of 720 mixed-sex 1-day-old White Pekin ducklings were randomly assigned into 4 groups: CON (control group, without OTA), OTA (fed a diet with 2 mg/kg OTA), CUR (ducks fed a diet with 400 mg/kg curcumin), and OTA + CUR (2 mg/kg OTA plus 400 mg/kg curcumin). Each treatment consisted of 6 replicates and 30 ducklings per replicate. Treatment lasted for 21 D. Results were analyzed by a two-tailed Student t test between 2 groups. Our results demonstrated that OTA treatment had the highest serum low-density lipoprotein (LDL) level among 4 groups. Compared with OTA group, OTA + CUR decreased serum LDL level (P < 0.05). OTA decreased liver catalase (CAT) activity in ducks (P < 0.05), while addition of curcumin in OTA group increased liver CAT activity (P < 0.05). 16S ribosomal RNA sequencing suggested that curcumin increased the richness indices (ACE index) and diversity indices (Simpson index) compared with OTA group (P < 0.05) and recovered the OTA-induced alterations in composition of the intestinal microbiota. Curcumin supplementation relieved the decreased abundance of butyric acid producing bacteria, including blautia, butyricicoccus, and butyricimonas, induced by OTA (P < 0.05). OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA. OTA treatment also increased SREBP-1c expression (P < 0.05). The curcumin group had the lowest expression of FAS and PPARG mRNA (P < 0.05) and the highest expression of NRF2 and HMOX1 mRNA. These results indicated that curcumin could alleviate OTA-induced oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.

Dietary fiber (DF) improves gastrointestinal health and has important associations with the alleviation of intestinal diseases and metabolic syndrome. However, due to DFs complex characteristics, such as solubility, viscosity, and fermentability, the mechanism in these was not consistent. As an herbivore, the goose has a prominent digestive ability to DF.

Melatonin (MEL) shows an anti-inflammatory effect and regulates intestinal microbiota communities in animals and humans; Ochratoxin A (OTA) induces liver inflammation through intestinal microbiota. However, it remains to know whether MEL alleviates the liver inflammation induced by OTA. In this study, MEL reversed various adverse effects induced by OTA. MEL recovered the swarming and motility of intestinal microbiota, decreased the accumulation of lipopolysaccharide (LPS), enhanced the tight junction proteins of jejunum and cecum segments; ultimately alleviated OTA-induced liver inflammation in ducks. However, it is worth noting that MEL still had positive effects on the OTA-exposed ducks after antibiotic treatment. These results suggest that both the maintenance of intestinal microbiota homeostasis and intestinal microbiota-independent manner involved the MEL anti-inflammatory function in OTA-induced liver inflammation. MEL represent a promising protective approach for OTA, even other mycotoxins.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.