Alginate Oligosaccharides Repair Liver Injury by Improving Anti-Inflammatory Capacity in a Busulfan-Induced Mouse Model.

Liver diseases are associated with many factors, including medicines and alcoholics, which have become a global problem. It is crucial to overcome this problem. Liver diseases always come with inflammatory complications, which might be a potential target to deal with this issue. Alginate oligosaccharides (AOS) have been demonstrated to have many beneficial effects, especially anti-inflammation. In this study, 40 mg/kg body weight (BW) of busulfan was intraperitoneally injected once, and then the mice were dosed with ddH2O or AOS 10 mg/kg BW every day by oral gavage for five weeks. We investigated AOS as a potential no-side-effect and low-cost therapy for liver diseases. For the first time, we discovered that AOS 10 mg/kg recovered liver injury by decreasing the inflammation-related factors. Moreover, AOS 10 mg/kg could improve the blood metabolites related to immune and anti-tumor effects, and thus, ameliorated impaired liver function. The results indicate that AOS may be a potential therapy to deal with liver damage, especially in inflammatory conditions.

Gut-Spleen Axis: Microbiota via Vascular and Immune Pathways Improve Busulfan-Induced Spleen Disruption.

Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.

Gut-Testis Axis: Microbiota Prime Metabolome To Increase Sperm Quality in Young Type 2 Diabetes.

Young type 2 diabetes (T2D) affects 15% of the population, with a noted increase in cases, and T2D-related male infertility has become a serious issue in recent years. The current study aimed to explore the improvements of alginate oligosaccharide (AOS)-modified gut microbiota on semen quality in T2D. The T2D was established in young mice of 5 weeks of age with a blood glucose level of 21.2 ± 2.2 mmol/L, while blood glucose was 8.7 ± 1.1 mM in control animals. We discovered that fecal microbiota transplantation (FMT) of AOS-improved microbiota (A10-FMT) significantly decreased blood glucose, while FMT of gut microbiota from control animals (Con-FMT) did not. Sperm concentration and motility were decreased in T2D to 10% to 20% of those in the control group, while A10-FMT brought about a recovery of around 5- to 10-fold. A10-FMT significantly increased small intestinal Allobaculum, while it elevated small intestinal and cecal Lactobacillus in some extent, blood butyric acid and derivatives and eicosapentaenoic acid (EPA), and testicular docosahexaenoic acid (DHA), EPA, and testosterone and its derivatives. Furthermore, A10-FMT improved liver functions and systemic antioxidant environments. Most importantly, A10-FMT promoted spermatogenesis through the improvement in the expression of proteins important for spermatogenesis to increase sperm concentration and motility. The underlying mechanisms may be that A10-FMT increased gut-beneficial microbes Lactobacillus and Allobaculum to elevate blood and/or testicular butyric acid, DHA, EPA, and testosterone to promote spermatogenesis and thus to ameliorate sperm concentration and motility. AOS-improved gut microbes could emerge as attractive candidates to treat T2D-diminished semen quality. IMPORTANCE A10-FMT benefits gut microbiota, liver function, and systemic environment via improvement in blood metabolome, consequently to favor the testicular microenvironment to improve spermatogenesis process and to boost T2D-diminished semen quality. We established that AOS-improved gut microbiota may be used to boost T2D-decreased semen quality and metabolic disease-related male subfertility.

Accumulation of Amino Acids and Flavonoids in Young Tea Shoots Is Highly Correlated With Carbon and Nitrogen Metabolism in Roots and Mature Leaves.

The quality of tea product and the metabolism of quality-related compounds in young shoots are significantly affected by the nitrogen(N) supply. However, little is known of the metabolic changes that take place in tea roots and mature leaves under different supplies, which has a large effect on the accumulation of quality-related compounds in young shoots. In this study, young shoots, mature leaves, and roots under different N conditions were subjected to metabolite profiling using gas chromatography and ultraperformance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry. The contents of free amino acids (e.g., theanine and glutamate) involved in N metabolism were significantly greater under high N than under low N, while a high N supply reduced soluble sugars (e.g., glucose) in all three tissues. Organic acids (e.g., malate, fumarate, α-ketoglutatare, and succinate) involved in tricarboxylic acid cycle remarkably increased as the nitrogen supply increased, which confirms that carbon (C) allocation was restricted by increasing the nitrogen supply, especially in mature leaves. RT-PCR results indicated that gene expression related to nitrogen assimilation significantly increased in roots with increasing nitrogen supply, which had a significant positive relationship with the level of free amino acids in young shoots. In addition, the expression of most genes involved in flavonoid synthesis was significantly upregulated under conditions of low nitrogen supply relative to high nitrogen supply in young shoot and roots. These data suggest that enhanced assimilation of N in tea roots and the coordinated regulation of C (sugars, organic acids, and flavonoids) and N(amino acids) in mature leaves can lead to a high accumulation of amino acids in young shoots. Furthermore, as the N supply increased, more C was partitioned into compounds containing N in mature leaves and roots, resulting in a decrease in flavonoids in young shoots. In conclusion, the accumulation of amino acids and flavonoids in young tea shoots is highly correlated with carbon and nitrogen metabolism in roots and mature leaves.