An update on T2-toxins: metabolism, immunotoxicity mechanism and human assessment exposure of intestinal microbiota.

Mycotoxins are naturally produced secondary metabolites or low molecular organic compounds produced by fungus with high diversification, which cause mycotoxicosis (food contamination) in humans and animals. T-2 toxin is simply one of the metabolites belonging to fungi trichothecene mycotoxin. Specifically, Trichothecenes-2 (T-2) mycotoxin of genus fusarium is considered one of the most hotspot agricultural commodities and carcinogenic compounds worldwide. There are well-known examples of salmonellosis in mice and pigs, necrotic enteritis in chickens, catfish enteric septicemia and colibacillosis in pigs as T-2 toxic agent. On the other hand, it has shown a significant reduction in the Salmonella population's aptitude in the pig intestinal tract. Although the impact of the excess Fusarium contaminants on humans in creating infectious illness is less well-known, some toxins are harmful; for example, salmonellosis and colibacillosis have been frequently observed in humans. More than 20 different metabolites are synthesized and excreted after ingestion, but the T-2 toxin is one of the most protuberant metabolites. Less absorption of mycotoxins in intestinal tract results in biotransformation of toxic metabolites into less toxic variants. In addition to these, effects of microbiota on harmful mycotoxins are not limited to intestinal tract, it may harm the other human vital organs. However, detoxification of microbiota is considered as an alternative way to decontaminate the feed for both animals and humans. These transformations of toxic metabolites depend upon the formation of metabolites. This study is complete in all perspectives regarding interactions between microbiota and mycotoxins, their mechanism and practical applications based on experimental studies.

An update on the economic burden of type 2 diabetes mellitus in China.

OBJECTIVES: This study aims to update the statistics on the economic burden of T2DM and to identify the factors affecting the economic costs of T2DM in China. METHODS: This study conducts a systematic review of the existing literature that has reported on the direct economic costs (mainly the direct medical resource consumption) and indirect economic costs (mainly non-medical costs and intangible costs) of T2DM as of 31 May 2019. RESULTS: The total expenditure on diabetes in China's western region is still relatively low. Additionally, the mean direct costs of T2DM are high in China's northern urban areas. However, compared to urban areas, in rural areas, the largest proportion of the total economic costs of T2DM is the mean indirect costs. Furthermore, age, sex, type and number of complications, type of medical insurance, diabetes duration, level of education, and income are the primary factors that influence the economic burden of T2DM. CONCLUSION: There is a considerable economic burden associated with T2DM in China. Therefore, to address the economic burden of T2DM, it is vital to take measures to reduce the prevalence rate of diabetes.

Promoting intestinal IgA production in mice by oral administration with anthocyanins.

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.

Downregulating testosterone levels enhance immunotherapy efficiency.

Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.

Biostimulating Gut Microbiome with Bilberry Anthocyanin Combo to Enhance Anti-PD-L1 Efficiency against Murine Colon Cancer.

Recent advances have revealed the essential role of gut microbiomes in the therapeutic efficiency of immune checkpoint inhibitors (ICIs). Inspired by biostimulation, a method using nutrients to accelerate the growth of soil microorganisms and the recovery of soil microbial consortia, here we propose a bilberry anthocyanin combo containing chitosan and low molecular citrus pectin (LCP), in which LCP-chitosan is used to encapsulate anthocyanins so to enhance its digestive stability and, moreover, modulate the microbiome more favorable for the PD-L1 blockade treatment. Using murine MC38 colon cancer as a model system, we examined the effects of the combo on modulating the gut microbiome and therapeutic efficiency of PD-L1 blockade treatment. It was shown that bilberry anthocyanins enriched the subdominant species, increased both the concentration and the proportion of butyrate in feces and enhanced intratumoral CD8+ T cell infiltrations. The application of the bilberry anthocyanin combo restored the species diversity of gut microbiome decreased by LCP-chitosan and achieved the best control of tumor growth. These preliminary results indicated unprecedented opportunities of probiotics combo in improving the therapeutic efficiency of immune checkpoint inhibitor through manipulating gut microbiome.

Bilberry anthocyanin extracts enhance anti-PD-L1 efficiency by modulating gut microbiota.

The undesirable low response rate is a major hurdle to garnering the maximum potential of immune checkpoint inhibitors in cancer treatments. Recent advances in exploring the effects of intestinal flora on the medical efficacy of immune checkpoint blockade have shed new light on the application of immune checkpoint inhibitors. Inspired by the prebiotic role of anthocyanin-rich extracts, we propose using bilberry anthocyanin extracts to modulate the composition of gut microbiota and eventually, promote the efficiency of immune checkpoint inhibitors. This study demonstrates the effectiveness of orally administered bilberry anthocyanin extracts in enhancing the anti-tumor efficiency of the PD-L1 antibody in the experimental mouse MC38 tumor model. We observed an increase in the fecal abundance of Clostridia and Lactobacillus johnsonii and improved effective community diversity. These findings reinforce the importance of intestinal flora composition and open up unprecedented opportunities in using natural compounds to enhance the efficacy of immune checkpoint inhibitors.