Food and drug design for gut microbiota-directed regulation: Current experimental landscape and future innovation.

Most diets and medications enhance host health via microbiota-dependent ways, but it is in the present situation of untargeted regulation. Non-targeted regulation may lead to the ineffectiveness of dietary supplements or drug treatment. Microbiota-directed food, aiming to improve diseases by targeting specific microbes without affecting other bacteria, have been proposed to deal with this problem. However, there is currently no universally applicable method to explore such foods or drugs. In this review, thirty studies on recent efforts in microbiota directed diets and medications are summarized from various databases. The methods used to find new foods and medications are primarily divided into four groups depending on the experimental models: in vivo and in vitro, as well as predictions based on bioinformatics. We also discuss their implementation, interpretation, and respective limitations, and describe the present situation. We further put forward a framework for microbiota-directed foods and medicine according to above methods and other microbiome manipulation, which will spur precision medicine.

Advances in fucoxanthin chemistry and management of neurodegenerative diseases.

BACKGROUND: Neurodegenerative diseases are chronic, currently incurable, diseases of the elderly, which are characterized by protein misfolding and neuronal damage. Fucoxanthin, derived from marine brown algae, presents a promising candidate for the development of effective therapeutic strategies. HYPOTHESIS AND PURPOSE: The relationship between neurodegenerative disease management and fucoxanthin has not yet been clarified. This study focuses on the fundamental mechanisms and targets of fucoxanthin in Alzheimer's and Parkinson's disease management, showing that communication between the brain and the gut contributes to neurodegenerative diseases and early diagnosis of ophthalmic diseases. This paper also presents, new insights for future therapeutic directions based on the integrated application of artificial intelligence. CONCLUSION: Fucoxanthin primarily binds to amyloid fibrils with spreading properties such as Aß, tau, and α-synuclein to reduce their accumulation levels, alleviate inflammatory factors, and restore mitochondrial membranes to prevent oxidative stress via Nrf2 and Akt signaling pathways, involving reduction of specific secretases. In addition, fucoxanthin may serve as a preventive diagnosis for neurodegenerative diseases through ophthalmic disorders. It can modulate gut microbes and has potential for the alleviation and treatment of neurodegenerative diseases.

The anti-hyperuricemic effects of green alga Enteromorpha prolifera polysaccharide via regulation of the uric acid transporters in vivo.

A novel polysaccharide obtained from Enteromorpha prolifera (EPP) was purified through diethylaminoethyl cellulose-52 and Sephadex G-75 chromatography. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance (NMR) spectroscopy were employed to analyse the structure of EPP. It mainly comprised rhamnose, glucuronic acid, galactose, arabinose, and xylose at a molar ratio of 20.45:12.74:10.99:5.84:1.95, and its average molecular weight was 46.56 kDa. The seven major glycosidic residues identified by NMR were as follows: →2)-α-L-Araf-(1→, →2)-α-L-Rhap-(1→, →4)-α-L-Rhap-(1→, →2,6)-ß-D-Galp-(1→, →4)-ß-D-GlcpA-(1→, →3,4)-ß-D-GlcpA-(1→, and →4)-ß-Xylp-(1→. The effect of EPP on hyperuricemic mice was determined by analysing correlative general physical parameters, renal histopathology, renal gene expressions, and gut microbiome. EPP significantly reduced serum uric acid (UA), serum blood urea nitrogen, serum xanthine oxidase (XOD), and hepatic XOD as well as improved histological parameters in hyperuricemic mice. Furthermore, mRNA and protein expression analyses showed the upregulation of UA excretion genes such as ABCG2, OAT1, and NPT1 and downregulation of UA resorption gene URAT1. Moreover, EPP maintained the stability of the intestinal flora and confirmed that Parasutterella is closely related to the regulation of hyperuricemia. This study is the first to demonstrate the anti-hyperuricemic activity of EPP and highlight its therapeutic potential for hyperuricemia-related diseases.

Physicochemical characterization and antioxidant effects of green microalga Chlorella pyrenoidosa polysaccharide by regulation of microRNAs and gut microbiota in Caenorhabditis elegans.

A novel polysaccharide from Chlorella pyrenoidosa (CPP) was separated and purified with the average molecular weight 15.8 kDa. It was composed of seven monosaccharides including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. FT-IR and NMR spectra analysis further revealed that CPP was an acidic polysaccharide consisting of ß-L-Arap-(1→, →2)-α-L-Rhap-(1→, ß-D-GlcpA-(1→, →4)-α-D-GalpA-(1→, →6)-ß-D-Glcp-(1→, →3)-ß-D-Manp-(1→, and →3, 6)-ß-D-Galp-(1→. The CPP treatment could effectively prolong lifespan of Caenorhabditis elegans under the oxidative stress conditions and inhibit the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as enhancing the level of superoxide dismutase (SOD). It could up-regulate the expressions of Daf-16 and Skn-1 genes via declining miR-48-3p, miR-48-5p, and miR-51-5p translocation. Moreover, 16S rRNA sequencing revealed that the CPP-enriched Faecalibacterium, Haemophilus, Vibrio, and Shewanella were strongly correlated with SOD, MDA, apoptosis, and ROS. These results indicated that CPP may be considered as a desired ingredient on regulating the aging and oxidative diseases.

Physicochemical Characterization of a Polysaccharide from Green Microalga Chlorella pyrenoidosa and Its Hypolipidemic Activity via Gut Microbiota Regulation in Rats.

A bioactive polysaccharide from microalga Chlorella pyrenoidosa (CPP) was successively prepared via DEAE-52 and G-100 columns. Nuclear magnetic resonance analysis showed that the main glycosidic bonds were composed of 1,2-linked-α-l-Fucp, 1,4-linked-α-l-Rhap, 1,4-linked-ß-l-Araf, 1-linked-α-d-Glcp, 1,3-linked-ß-d-GlcpA, 1,4-linked-ß-d-Xylp, and 1,3,6-linked-ß-d-Manp. Its molecular weight was 5.63 × 106 Da. The hypolipidemic effect and intestinal flora regulation of CPP on diet-induced rats were evaluated through histopathology and biochemistry analyses. CPP could improve plasma and liver lipid metabolism and accelerate the metabolism of the cecal total bile acids and short-chain fatty acids. CPP has also upregulated the adenosine-monophosphate-activated protein kinase α and downregulated the acetyl-CoA carboxylase, sterol regulatory element-binding protein 1c, and ß-hydroxy ß-methylglutaryl-CoA expressions. Moreover, with the 16S rRNA gene sequencing, it was revealed that the composition of intestinal flora changed drastically after treatment, such as the bloom of Coprococcus_1, Lactobacillus, and Turicibacter, whereas there was a strong reduction of the [Ruminococcus]_gauvreauii_group. The above results illustrated that CPP might be served as an effective ingredient to ameliorate lipid metabolism disorders and intestinal flora in hyperlipidemia rats.