Gut mycobiome and metabolic diseases: The known, the unknown, and the future.

Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide. In recent years, most research on the role of gut microbes in metabolic diseases has focused on bacteria, whereas fungal microbes have been neglected. This review aims to provide a comprehensive overview of gut fungal alterations in T2DM, obesity, and NAFLD, and to discuss the mechanisms associated with disease development. In addition, several novel strategies targeting gut mycobiome and/or their metabolites to improve T2DM, obesity and NAFLD, including fungal probiotics, antifungal drugs, dietary intervention, and fecal microbiota transplantation, are critically discussed. The accumulated evidence suggests that gut mycobiome plays an important role in the occurrence and development of metabolic diseases. The possible mechanisms by which the gut mycobiome affects metabolic diseases include fungal-induced immune responses, fungal-bacterial interactions, and fungal-derived metabolites. Candida albicans, Aspergillus and Meyerozyma may be potential pathogens of metabolic diseases because they can activate the immune system and/or produce harmful metabolites. Moreover, Saccharomyces boulardii, S. cerevisiae, Alternaria, and Cochliobolus fungi may have the potential to improve metabolic diseases. The information may provide an important reference for the development of new therapeutics for metabolic diseases based on gut mycobiome.

Therapeutic Effect of Curcumin on Metabolic Diseases: Evidence from Clinical Studies.

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus Curcuma. In recent years, clinical trials using curcumin for the treatment of metabolic diseases have been increasing. In this review, we provide a timely and comprehensive summary of the clinical progress of curcumin in the treatment of three metabolic diseases, namely type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). The therapeutic effects and underlying mechanisms of curcumin on these three diseases are presented categorically. Accumulating clinical evidence demonstrates that curcumin has good therapeutic potential and a low number of side effects for the three metabolic diseases. It can lower blood glucose and lipid levels, improve insulin resistance and reduce inflammation and oxidative stress. Overall, curcumin may be an effective drug for the treatment of T2DM, obesity and NAFLD. However, more high-quality clinical trials are still required in the future to verify its efficacy and determine its molecular mechanisms and targets.

Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies.

With the continuous improvement of people's living standard, the incidence of metabolic diseases is gradually increasing in recent years. There is growing interest in finding drugs to treat metabolic diseases from natural compounds due to their good efficacy and limited side effects. Over the past few decades, many phytochemicals derived from natural plants, such as berberine, curcumin, quercetin, resveratrol, rutin, and hesperidin, have been shown to have good pharmacological activity against metabolic diseases in preclinical studies. More importantly, clinical trials using these phytochemicals to treat metabolic diseases have been increasing. This review comprehensively summarizes the clinical progress of phytochemicals derived from natural plants in the treatment of several metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). Accumulating clinical evidence shows that a total of 18 phytochemicals have good therapeutic effects on the three metabolic diseases by lowering blood glucose and lipid levels, reducing insulin resistance, enhancing insulin sensitivity, increasing energy expenditure, improving liver function, and relieving inflammation and oxidative stress. The information will help us better understand the medicinal value of these phytochemicals and promote their clinical application in the treatment of metabolic diseases.

Traditional Tibetan medicine to fight against COVID-19: Basic theory and therapeutic drugs.

The Coronavirus Diseases 2019 (COVID-19) has been rapidly spreading globally and has caused severe harm to the health of people and a substantial social burden. In response to this situation, experts around the world have considered various treatments, including the use of traditional medicine. Traditional Tibetan medicine (TTM), one of the traditional medicines in China, has played an important role in the treatment of infectious diseases in history. It has formed a solid theoretical foundation and accumulated rich experience in the treatment of infectious diseases. In this review, we provide a comprehensive introduction to the basic theory, treatment strategies, and commonly used drugs of TTM for the treatment of COVID-19. In addition, the efficacies and potential mechanisms of these TTM drugs against COVID-19 are discussed based on available experimental data. This review may provide important information for the basic research, clinical application and drug development of traditional medicines for the treatment of COVID-19 or other infectious diseases. More pharmacological studies are needed to reveal the therapeutic mechanisms and active ingredients of TTM drugs in the treatment of COVID-19.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy.

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Nucleotide binding as an allosteric regulatory mechanism for Akkermansia muciniphila ß-N-acetylhexosaminidase Am2136.

ß-N-acetylhexosaminidases (EC3.2.1.52), which belong to the glycosyl hydrolase family GH20, are important enzymes for oligosaccharides modification. Numerous microbial ß-N-acetylhexosaminidases have been investigated for applications in biology, biomedicine and biotechnology. Akkermansia muciniphila is an anaerobic intestinal commensal bacterium which possesses specific ß-N-acetylhexosaminidases for gut mucosal layer colonization and mucin degradation. In this study, we assessed the in vitro mucin glycan cleavage activity of the A. muciniphila ß-N-acetylhexosaminidase Am2136 and demonstrated its ability that hydrolyzing the ß-linkages joining N-acetylglucosamine to a wide variety of aglycone residues, which indicated that Am2136 may be a generalist ß-N-acetylhexosaminidase. Structural and enzyme activity assay experiments allowed us to probe the essential function of the inter-domain interactions in ß23-ß33. Importantly, we revealed that the hydrolysis activity of Am2136 was enhanced by nucleotides. We further speculated that this activation mechanism might be associated with the conformational motions between domain III and IV. To our knowledge, this is the first report of nucleotide effector regulated ß-N-acetylhexosaminidase, to reveal its novel biological functions. These findings contribute to understanding the distinct properties within the GH20 family and lay a certain foundation to develop controllable glycan hydrolyzing catalysts.Abbreviations: OD600 - optical cell densities at 600 nm; LB - Luria-Bertani; IPTG - isopropyl ß-D-1-thiogalactopyranoside; PMSF - phenylmethanesulfonyl fluoride; rmsd - root mean square deviation; GlcNAc - N-acetyl-ß-D-glucosamine; GalNAc - N-acetyl-ß-D-galactosamine; Gal - galactose.

A Food-Energy-Water Nexus approach for land use optimization.

Allocation and management of agricultural land is of emergent concern due to land scarcity, diminishing supply of energy and water, and the increasing demand of food globally. To achieve social, economic and environmental goals in a specific agricultural land area, people and society must make decisions subject to the demand and supply of food, energy and water (FEW). Interdependence among these three elements, the Food-Energy-Water Nexus (FEW-N), requires that they be addressed concertedly. Despite global efforts on data, models and techniques, studies navigating the multi-faceted FEW-N space, identifying opportunities for synergistic benefits, and exploring interactions and trade-offs in agricultural land use system are still limited. Taking an experimental station in China as a model system, we present the foundations of a systematic engineering framework and quantitative decision-making tools for the trade-off analysis and optimization of stressed interconnected FEW-N networks. The framework combines data analytics and mixed-integer nonlinear modeling and optimization methods establishing the interdependencies and potentially competing interests among the FEW elements in the system, along with policy, sustainability, and feedback from various stakeholders. A multi-objective optimization strategy is followed for the trade-off analysis empowered by the introduction of composite FEW-N metrics as means to facilitate decision-making and compare alternative process and technological options. We found the framework works effectively to balance multiple objectives and benchmark the competitions for systematic decisions. The optimal solutions tend to promote the food production with reduced consumption of water and energy, and have a robust performance with alternative pathways under different climate scenarios.