Exploring Longitudinal Gut Microbiome towards Metabolic Functional Changes Associated in Atopic Dermatitis in Early Childhood.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease that has been associated with changes in gut microbial composition in early life. However, there are limited longitudinal studies examining the gut microbiome in AD. This study aimed to explore taxonomy and metabolic functions across longitudinal gut microbiomes associated with AD in early childhood from 9 to 30 months of age using integrative data analysis within the Thai population. Our analysis revealed that gut microbiome diversity was not different between healthy and AD groups; however, significant taxonomic differences were observed. Key gut bacteria with short-chain fatty acids (SCFAs) production potentials, such as Anaerostipes, Butyricicoccus, Ruminococcus, and Lactobacillus species, showed a higher abundance in the AD group. In addition, metabolic alterations between the healthy and AD groups associated with vitamin production and host immune response, such as biosynthesis of menaquinol, succinate, and (Kdo)2-lipid A, were observed. This study serves as the first framework for monitoring longitudinal microbial imbalances and metabolic functions associated with allergic diseases in Thai children during early childhood.

Revealing holistic metabolic responses associated with lipid and docosahexaenoic acid (DHA) production in Aurantiochytrium sp. SW1.

Aurantiochytrium sp. SW1, a marine thraustochytrid, has been regarded as a potential candidate as a docosahexaenoic acid (DHA) producer. Even though the genomics of Aurantiochytrium sp. are available, the metabolic responses at a systems level are largely unknown. Therefore, this study aimed to investigate the global metabolic responses to DHA production in Aurantiochytrium sp. through transcriptome and genome-scale network-driven analysis. Of a total of 13,505 genes, 2527 differentially expressed genes (DEGs) were identified in Aurantiochytrium sp., unravelling the transcriptional regulations behinds lipid and DHA accumulation. The highest number of DEG were found for pairwise comparison between growth phase and lipid accumulating phase where a total of 1435 genes were down-regulated with 869 genes being up-regulated. These uncovered several metabolic pathways that contributing in DHA and lipid accumulation including amino acid and acetate metabolism which involve in the generation of crucial precursors. Upon applying network-driven analysis, hydrogen sulphide was found as potential reporter metabolite that could be associated with the genes related to acetyl-CoA synthesis for DHA production. Our findings suggest that the transcriptional regulation of these pathways is a ubiquitous feature in response to specific cultivation phases during DHA overproduction in Aurantiochytrium sp. SW1.

Faecal Proteomics and Functional Analysis of Equine Melanocytic Neoplasm in Grey Horses.

Equine melanocytic neoplasm (EMN) is a common disease in older grey horses. The purpose of this study was to examine the potential proteins throughout EMN stages from faecal proteomic outlining using functional analysis. Faecal samples were collected from the rectum of 25 grey horses divided into three groups; normal group without EMN (n = 10), mild EMN (n = 6) and severe EMN (n = 9). Based on the results, 5910 annotated proteins out of 8509 total proteins were assessed from proteomic profiling. We observed differentially expressed proteins (DEPs) between the normal group and the EMN group, and 109 significant proteins were obtained, of which 28 and 81 were involved in metabolic and non-metabolic functions, respectively. We found 10 proteins that play a key role in lipid metabolism, affecting the tumour microenvironment and, consequently, melanoma progression. Interestingly, FOSL1 (FOS like 1, AP-1 transcription factor subunit) was considered as a potential highly expressed protein in a mild EMN group involved in melanocytes cell and related melanoma. Diacylglycerol kinase (DGKB), TGc domain-containing protein (Tgm2), structural maintenance of chromosomes 4 (SMC4) and mastermind-like transcriptional coactivator 2 (MAML2) were related to lipid metabolism, facilitating melanoma development in the severe-EMN group. In conclusion, these potential proteins can be used as candidate biomarkers for the monitoring of early EMN, the development of EMN, further prevention and treatment.

Analyzing Predominant Bacterial Species and Potential Short-Chain Fatty Acid-Associated Metabolic Routes in Human Gut Microbiome Using Integrative Metagenomics.

Gut microbiome plays an essential role in host health, and there is interest in utilizing diet to modulate the composition and function of microbial communities. Copra meal hydrolysate (CMH) is commonly used as a natural additive to enhance health. However, the gut microbiome is largely unknown at species level and is associated with metabolic routes involving short-chain fatty acids (SCFAs). In this study, we aimed to analyze, using integrative metagenomics, the predominant species and metabolic routes involved in SCFAs production in the human gut microbiome after treatment with CMH. The effect of CMH treatment on the Thai gut microbiome was demonstrated using 16S rRNA genes with whole-metagenome shotgun (WMGS) sequencing technology. Accordingly, these results revealed that CMH has potentially beneficial effects on the gut microbiome. Twelve predominant bacterial species, as well as their potential metabolic routes, were involved in cooperative microbiome networks under sugar utilization (e.g., glucose, mannose, or xylose) and energy supply (e.g., NADH and ATP) in relation to SCFAs biosynthesis. These findings suggest that CMH may be used as a potential prebiotic diet for modulating and maintaining the gut microbiome. To our knowledge, this is the first study to reveal the predominant bacterial species and metabolic routes in the Thai gut microbiome after treatment with potential prebiotics.

Preliminary Study: Proteomic Profiling Uncovers Potential Proteins for Biomonitoring Equine Melanocytic Neoplasm.

Equine melanocytic neoplasm (EMN) is a cutaneous neoplasm and is mostly observed in aged grey horses. This preliminary study aimed to identify potential proteins to differentiate normal, mild and severe EMN from serum proteomic profiling. Serum samples were collected from 25 grey horses assigned to three groups: normal (free of EMN; n = 10), mild (n = 6) and severe EMN (n = 9). To explore the differences in proteins between groups, proteomic profiling and analysis were employed. Accordingly, 8241 annotated proteins out of 8725 total proteins were compared between normal and EMN groups and inspected based on differentially expressed proteins (DEPs). Through DEP analysis, 95 significant DEPs differed between normal and EMN groups. Among these DEPs, 41 significant proteins were categorised according to protein functions. Based on 41 significant proteins, 10 were involved in metabolism and 31 in non-metabolism. Interestingly, phospholipid phosphatase6 (PLPP6) and ATPase subunit alpha (Na+/K+-ATPase) were considered as potential proteins uniquely expressed in mild EMN and related to lipid and energy metabolism, respectively. Non-metabolism-related proteins (BRCA1, phosphorylase B kinase regulatory subunit: PHKA1, tyrosine-protein kinase receptor: ALK and rho-associated protein kinase: ROCK1) correlated to melanoma development differed among all groups. The results of our study provide a foundation for early EMN biomonitoring and prevention.

Analysis of the infant gut microbiome reveals metabolic functional roles associated with healthy infants and infants with atopic dermatitis using metaproteomics.

The infant gut microbiome consists of a complex and diverse microbial community. Comprehensive taxonomic and metabolic functional knowledge about microbial communities supports medical and biological applications, such as fecal diagnostics. Among the omics approaches available for the investigation of microbial communities, metaproteomics-based analysis is a very powerful approach; under this method, the activity of microbial communities is explored by investigating protein expression within a sample. Through use of metaproteomics, this study aimed to investigate the microbial community composition of the infant gut to identify different key proteins playing metabolic functional roles in the microbiome of healthy infants and infants with atopic dermatitis in a Thai population-based birth cohort. Here, 18 fecal samples were analyzed by liquid chromatography-tandem mass spectrometry to conduct taxonomic, functional, and pathway-based protein annotation. Accordingly, 49,973 annotated proteins out of 68,232 total proteins were investigated in gut microbiome samples and compared between the healthy and atopic dermatitis groups. Through differentially expressed proteins (DEPs) analysis, 130 significant DEPs were identified between the healthy and atopic dermatitis groups. Among these DEPs, eight significant proteins were uniquely expressed in the atopic dermatitis group. For instance, triosephosphate isomerase (TPI) in Bifidobacteriaceae in the genus Alloscardovia and demethylmenaquinone methyltransferase (DMM) in Bacteroides were shown to potentially play metabolic functional roles related to disease. PPI network analysis revealed seven reporter proteins showing metabolic alterations between the healthy and disease groups associated with the biosynthesis of ubiquinone and other quinones as well as the energy supply. This study serves as a scaffold for microbial community-wide metabolic functional studies of the infant gut microbiome in relation to allergic disease.

Dissecting metabolic behavior of lipid over-producing strain of Mucor circinelloides through genome-scale metabolic network and multi-level data integration.

Lipid accumulation is an important cellular process of oleaginous microorganisms. To dissect metabolic behavior of oleaginous Zygomycetes, the lipid over-producing strain, Mucor circinelloides WJ11, was subjected for omics-scale analysis. The genome annotation was improved and used for construction of genome-scale metabolic network of WJ11 strain. Then, the quality of the metabolic network was enhanced by incorporating gene and protein expression data. In addition to the known oleaginous genes, our results showed a number of newly identified unique genes of WJ11 strain, which involved in central carbon metabolism, lipid, amino acid and nitrogen metabolisms. The systematic compilations indicated the additional metabolic routes with the involvement in supplying precursors (acetyl-CoA, NADPH and fatty acyl substrate) for fatty acid and lipid biosynthesis. Interestingly, amino acid metabolism played a substantial role in responsive mechanism of the fungal cells to nutrient imbalance circumstance through lipogenesis as the finding of reporter metabolites (l-methionine, l-glutamate, l-aspartate, l-asparagine and l-glutamine) at lipid-accumulating stage. The cooperative function of certain lipid-degrading enzymes at the particular growth stage was elucidated by integrating the metabolic networks with gene expression data. The unique feature of carotenoid biosynthetic route in WJ11 strain was also identified by protein domain analysis. Taken together, there were cross-functional metabolisms in regulating lipid biosynthesis and retaining high level of cellular lipids in the representative of lipid over-producing strains.