Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

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.

Ochratoxin A induces abnormal tryptophan metabolism in the intestine and liver to activate AMPK signaling pathway.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin widely present in raw food and feed materials and is mainly produced by Aspergillus ochraceus and Penicillium verrucosum. Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder, especially Bacteroides plebeius (B. plebeius) overgrowth. However, whether OTA or B. plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown. This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver. MATERIALS AND METHODS: A total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups. The control group was given 0.1 mol/L NaHCO3 solution, and the OTA group was given 235 µg/kg body weight OTA for 14 consecutive days. Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics. AMPK-related signaling pathway factors were analyzed by Western blotting and mRNA expression. RESULTS: Metabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intestinal nicotinuric acid levels, the downstream product of tryptophan metabolism, which were significantly negatively correlated with B. plebeius abundance. In contrast, OTA induced a significant increase in indole-3-acetamide levels, which were positively correlated with B. plebeius abundance. Simultaneously, OTA decreased the levels of ATP, NAD+ and dipeptidase in the liver. Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine, anthranilic acid and nicotinic acid. Moreover, OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein. CONCLUSION: OTA decreased the level of nicotinuric acid in the intestinal tract, which was negatively correlated with B. plebeius abundance. The abnormal metabolism of tryptophan led to a deficiency of NAD+ and ATP in the liver, which in turn activated the AMPK signaling pathway. Our results provide new insights into the toxic mechanism of OTA, and tryptophan metabolism might be a target for prevention and treatment.

Crosstalk between Mycotoxins and Intestinal Microbiota and the Alleviation Approach via Microorganisms.

Mycotoxins are secondary metabolites produced by fungus. Due to their widespread distribution, difficulty in removal, and complicated subsequent harmful by-products, mycotoxins pose a threat to the health of humans and animals worldwide. Increasing studies in recent years have highlighted the impact of mycotoxins on the gut microbiota. Numerous researchers have sought to illustrate novel toxicological mechanisms of mycotoxins by examining alterations in the gut microbiota caused by mycotoxins. However, few efficient techniques have been found to ameliorate the toxicity of mycotoxins via microbial pathways in terms of animal husbandry, human health management, and the prognosis of mycotoxin poisoning. This review seeks to examine the crosstalk between five typical mycotoxins and gut microbes, summarize the functions of mycotoxins-induced alterations in gut microbes in toxicological processes and investigate the application prospects of microbes in mycotoxins prevention and therapy from a variety of perspectives. The work is intended to provide support for future research on the interaction between mycotoxins and gut microbes, and to advance the technology for preventing and controlling mycotoxins.

Dietary fibers with different viscosity regulate lipid metabolism via ampk pathway: roles of gut microbiota and short-chain fatty acid.

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. Therefore, we choose low, medium, and high viscosity DFs (respectively resistant starch-3 []RS], inulin [INU], and ß-glucan [GLU]) as Magang goose diet treatment for 4 wk, to investigate the effect and potential mechanism of different viscosities DFs on the growth and development process of goose. In summary, three degrees of viscous DFs could decrease the mechanismic lipid level of geese by promoting acid-producing bacteria and short-chain fatty acid (SCFA) production, therefore, activating AMPK pathway-related genes through the gut-liver axis. High viscous DF has a greater lipid-lowering effect on geese, while medium viscous DF has preferable intestinal mucosal protection.

Combined Analysis of the Effects of Exposure to Blue Light in Ducks Reveals a Reduction in Cholesterol Accumulation Through Changes in Methionine Metabolism and the Intestinal Microbiota.

Monochromatic light is widely used in industry, medical treatment, and animal husbandry. Green-blue light has been found to stimulate the proliferation of satellite cells and the results of studies on the effects of blue light on poultry vary widely. It would be worthwhile to study the effect of blue light on poultry growth and how exposure to blue light affects metabolism and the intestinal microbiota. In this study, we irradiated Cherry Valley ducks with 460 nm wavelength light (blue light) for 3 weeks to explore the effects of blue light in comparison to those of white light (combined wavelength light) on animal growth and development. Our results showed that, under exposure to blue light, the body weight and average daily feed intake of ducks were decreased, but the leg muscle and relative length of the intestine were increased. Exposure to blue light chiefly enhanced the anti-inflammatory and antioxidant capacities of the animal and decreased lipid levels in serum and liver. Metabolomic analysis revealed that blue light heightened cysteine and methionine metabolism, and increased serum taurine and primary bile acid levels, as well as up-regulating the metabolites L-carnitine and glutamine. Treatment with blue light significantly increased the beta diversity of intestinal microbiota and the relative abundances of bile acid hydrolase-producing bacteria, especially Alistipes. These changes promote the synthesis of secondary bile acids to further enhance lipid metabolism in the host, thereby reducing cholesterol accumulation in ducks. These results should help us better understand the effects of exposure to blue light on metabolite levels and the intestinal microbiota, and suggest that it may be possible to use colored light to control the development of livestock and poultry.

Persistent Purine Metabolic Abnormality Induces the Aggravation of Visceral Inflammation and Intestinal Microbiota Dysbiosis in Magang Goose.

Gout is a disease involving abnormal purine metabolism that is widespread in mammals and birds. Goose is especially susceptible for gout in early stage. However, a few studies investigated the ontogenetic pattern of goslings with purine metabolic abnormality. Our studies were conducted to investigate whether persistent purine metabolic abnormality would lead to aggravation of visceral inflammation and intestinal microbiota dysbiosis in goose. A total of 132 1-day-old Magang geese were randomly divided into six replicates and fed a high-calcium and protein meal-based diet from 1 to 28 days. The experiment lasted for 28 days. Liver and kidney damages were observed in 14- and 28-day-old Magang geese, and liver inflammation increased with increasing age. In 28-day-old Magang geese, serum CAT and liver GSH-Px activity were significantly reduced. Furthermore, jejunum intestinal barrier was impaired and the abundance of Bacteroides was significantly reduced at the genus level. Collectively, the high-calcium and high-protein (HCP) meal-based diet caused liver and kidney damage in 28-day-old Magang geese, leading to hyperuricemia and gout symptoms, and the intestinal barrier is impaired and the intestinal flora is disrupted.

Melatonin alleviates Ochratoxin A-induced liver inflammation involved intestinal microbiota homeostasis and microbiota-independent manner.

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.