Metabolomic analysis of retinopathy stages and amputation in type 2 diabetes.

BACKGROUND: Diabetic retinopathy (DR) and limb amputation are frequent complications of diabetes that cannot always be explained by blood glucose control. Metabolomics is a science that is currently being explored in the search for biomarkers or profiles that identify clinical conditions of interest. OBJECTIVE: This study aimed to analyze, using a metabolomic approach, peripheral blood samples from type 2 diabetes mellitus (DM2) individuals, compared with those with diabetic retinopathy and limb amputation. METHODS: The sample consisted of 128 participants, divided into groups: control, DM2 without DR (DM2), non-proliferative DR (DRNP), proliferative DR (DRP), and DM2 amputated (AMP). Metabolites from blood plasma were classified by spectra using nuclear magnetic resonance (NMR), and the metabolic routes of each group using metaboanalyst. RESULTS: We identified that the metabolism of phenylalanine, tyrosine, and tryptophan was discriminant for the DRP group. Histidine biosynthesis, on the other hand, was statistically associated with the AMP group. The results of this work consolidate metabolites such as glutamine and citrulline as discriminating for DRP, and the branched-chain amino acids as important for DR. CONCLUSIONS: The results demonstrate the relationship between the metabolism of ketone bodies, with acetoacetate metabolite being discriminating for the DRP group and histidine being a significant metabolite in the AMP group, when compared to the DM2 group.

Unrevealing the in vitro impacts of Cereus jacamaru DC. cladodes flour on potentially probiotic strains, selected bacterial populations, and metabolic activity of human intestinal microbiota.

This study investigated the potential impacts of the flour from Cereus jamacaru cactus cladodes (CJF), a cactus native to the Brazilian Caatinga biome, on the growth and metabolism of different potentially probiotic strains, as well as on the abundance of selected intestinal bacterial populations and microbial metabolic activity during in vitro colonic fermentation with a pooled human fecal inoculum. Cultivation of the probiotics in a medium with C. jamacaru cladodes flour (20 g/L) resulted in viable cell counts of up to 9.8 log CFU/mL, positive prebiotic activity scores (0.73-0.91), decreased pH and sugar contents, and increased lactic, acetic, and propionic acid production over time, indicating enhanced probiotic growth and metabolic activity. CJF overall increased the relative abundance of Lactobacillus spp./Enterococcus spp. (2.12-3.29%) and Bifidobacterium spp. (4.08-4.32%) and decreased the relative abundance of Bacteroides spp./Prevotella spp. (8.35-6.81%), Clostridium histolyticum (6.91-3.59%), and Eubacterium rectale/Clostridium coccoides (7.70-3.95%) during 48 h of an in vitro colonic fermentation using a pooled human fecal inoculum. CJF stimulated the microbial metabolic activity, with decreased pH, sugar consumption, lactic and short-chain fatty acid production, alterations in overall metabolic profiling and phenolic compound contents, and maintenance of high antioxidant capacity during colonic fermentation. These results show that CJF stimulated the growth and metabolic activity of distinct potential probiotics, increased the relative abundance of beneficial intestinal bacterial groups, and stimulated microbial metabolism during in vitro colonic fermentation. Further studies using advanced molecular technologies and in vivo experimental models could forward the investigation of the potential prebiotic properties of CJF.

Revealing the Potential Impacts of Nutraceuticals Formulated with Freeze-Dried Jabuticaba Peel and Limosilactobacillus fermentum Strains Candidates for Probiotic Use on Human Intestinal Microbiota.

This study evaluated the impacts of novel nutraceuticals formulated with freeze-dried jabuticaba peel (FJP) and three potentially probiotic Limosilactobacillus fermentum strains on the abundance of bacterial groups forming the human intestinal microbiota, metabolite production, and antioxidant capacity during in vitro colonic fermentation. The nutraceuticals had high viable counts of L. fermentum after freeze-drying (≥ 9.57 ± 0.09 log CFU/g). The nutraceuticals increased the abundance of Lactobacillus ssp./Enterococcus spp. (2.46-3.94%), Bifidobacterium spp. (2.28-3.02%), and Ruminococcus albus/R. flavefaciens (0.63-4.03%), while decreasing the abundance of Bacteroides spp./Prevotella spp. (3.91-2.02%), Clostridium histolyticum (1.69-0.40%), and Eubacterium rectale/C. coccoides (3.32-1.08%), which were linked to positive prebiotic indices (> 1.75). The nutraceuticals reduced the pH and increased the sugar consumption, short-chain fatty acid production, phenolic acid content, and antioxidant capacity, besides altering the metabolic profile during colonic fermentation. The combination of FJP and probiotic L. fermentum is a promising strategy to produce nutraceuticals targeting intestinal microbiota.

Dolastane diterpenes from Canistrocarpus cervicornis and their effects in modulation of drug resistance in Staphylococcus aureus.

One new diterpene (4R,7R,14S)-4α,7α-diacetoxy-10-one-14α-hydroxydolasta-1(15),8-diene (1), and five known compounds (4R,7R,14S)-4α,7α-diacetoxy-14α-hydroxydolasta-1(15),8-diene (2), (4R,14S)-4α,14α-dihydroxydolasta-1(15),8-diene (3), (4S,9R,14S)-4α-acetoxy-9ß,14α-dihydroxydolasta-1(15),7-diene (4), 4-acetoxy-14-hydroxydolasta-1(15),7,9-triene (5) and isolinearol (6), were isolated from Canistrocarpus cervicornis. In this study, dolastane diterpenes were isolated from the alga C. cervicornis and evaluated as modifiers of antibiotic activity in Staphylococcus aureus: SA-1199B, which overexpresses the norA gene RN-4220, which encodes for the protein efflux of macrolides (MRSA), and IS-58 which has the gene encoding the protein TetK. The minimum inhibitory concentrations (MICs) for norfloxacin, tetracycline and erythromycin were determined by the microdilution broth nutrient in the absence and presence of diterpenes at a sub-inhibitory concentration (MIC/4). The extracts of C. cervicornis and isolated diterpenes showed no antibacterial activity, but showed modulatory activity, decreasing the MIC of antibiotics by 4-256 fold. The results indicate that seaweed extracts and diterpenes are potential sources of antibiotic adjuvant, acting as potential inhibitors of efflux pump.