Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice

Sepsis progression is significantly associated with the disruption of gut eubiosis.However,the modulatory mechanisms of gut microbiota operating during sepsis are still unclear.Herein,we investigated how gut commensals impact sepsis development in a pre-clinical model.Cecal ligation and puncture(CLP)surgery was used to establish polymicrobial sepsis in mice.Mice depleted of gut microbiota by an antibiotic cocktail(ABX)exhibited a significantly higher level of mortality than controls.As determined by metabolomics analysis,ABX treatment has depleted many metabolites,and subsequent supplementation with L-rhamnose(rhamnose,Rha),a bacterial carbohydrate metabolite,exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis,which in turn improved organ damage and mortality.Mechanistically,rhamnose binds directly to and activates the solute carrier family 12(potassium-chloride symporter),member 4(SLC12A4)in macrophages and promotes phagocytosis by activating the small G-proteins,Ras-related C3 botulinum toxin substrate1(Rac1)and cell division control protein 42 homolog(Cdc42).Interestingly,rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients.In conclusion,by identifying SLC12A4 as the host interacting protein,we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Hypolipidemic effect of chromium-modified enzymatic product of sulfated rhamnose polysaccharide from Enteromorpha prolifera in type 2 diabetic mice

Sulfated rhamnose polysaccharide(SRP)derived from Enteromorpha prolifera is a metal-ion chelating agent that could potentially be used to treat diabetes.The aim of our study was to determine the effect of a variant of SRP on DIABETES.First,we synthesized and characterized SRPE-3 chromium(III)[SRPE-3-Cr(III)]complex using an enzymatic method.The maximum chelation rate was 18.2%under optimal chelating conditions of pH 6.0,time 4 h,and temperature 60°C.Fourier transform infrared spectroscopy results showed important sites for Cr(III)-binding were O–H and C=O groups.We then studied the hypolipidemic effects of SRPE-3-Cr(III)on type 2 diabetes mellitus(T2DM)induced by a high-fat,high-sucrose diet(HFSD).Decreased blood glucose content,body fat ratio,serum TG,TC,LDL-C,and increased serum HDL-C were observed after treatment with SRPE-3-Cr(III).In addition,SRPE-3-Cr(III)significantly reduced leptin,resistin,and TNF-αlevels,and increased adiponectin contents relative to T2DM.Histopathology results also showed that SRPE-3-Cr(III)could alleviate the HFSD-lesioned tissues.SRPE-3-Cr(III)also improved lipid metabolism via a reduction in aspartate aminotransferase,alanine aminotransferase,fatty acid synthase,and acetyl-CoA carboxylase activities in the liver.SRPE-3-Cr(III)at low doses exhibited better lipid-lowering activities,hence,could be considered to be a novel compound to treat hyperlipidemia and also act as an anti-diabetic agent.

Synthesis of di-and tetrasaccharide containing 6-deoxytalose from the O-antigenic polysaccharide of B. pseudomallei strain 304b

Synthesis of the disaccharide [3-D-Glup-（1→3）-6-deoxy-α-L-Talp Ⅱ, and its dimer Ⅲ from the O-antigenic polysaccharide of Burkholderia pseudomallei strain 304b, were achieved through assembly of suitably synthesized building blocks, 4-methox- ylphenyl 6-deoxy-2,4-di-O-benzoyl-α-L-talopyranoside （7）, 3-O-allyl-2,4,6-tri-O-benzoyl-α,β-D-glucopyranosyl trichloroacetimi- date （8） and 2,3,4,6-tetra-O-benzoyl-α,β-D-glucopyranosyl trichloroacetimidate （11）. The total yield of Ⅲ from 4-methoxylphenyl 2.3-O-isopropvlidene-α-L-rhamnoovranoside （1） was 18%.

Rapid Method for the Determination of Total Monosaccharide in <i>Enterobacter cloacae</i>Strains Using Fourier Transform Infrared Spectroscopy

Fourier Transform Infrared Spectroscopy (FTIR) was used to quantify total monosaccharide content in the bacterium Enterobacter cloacae and several of its biofilm mutants. Bacterial biofilm samples were grown on trypticase soy agar, and 30 μL aliquots of aqueous sample bacterial plus biofilm were deposited into the center of barium fluoride crystals and dried at 50°C for 1-hour before being scanned by FTIR. The total amounts of monosaccharides were estimated using the absorbance of the mono-saccharide peak, 1192 - 958 cm–1, and normalized using the amide II peak, 1585 - 1483 cm–1. This method provided a linear correlation between the absorbance of the monosaccharide peak and concentration of monosaccharide in standard monosaccharides, fructose, glucose, mannose, and rhamnose, over a concentration range of 0.5 - 2.0 mg/mL.