Holed up, but thriving: Impact of multitrophic cryoconite communities on glacier elemental cycles.

Cryoconite holes (water and sediment-filled depressions), found on glacier surfaces worldwide, serve as reservoirs of microbes, carbon, trace elements, and nutrients, transferring these components downstream via glacier hydrological networks. Through targeted amplicon sequencing of carbon and nitrogen cycling genes, coupled with functional inference-based methods, we explore the functional diversity of these mini-ecosystems within Antarctica and the Himalayas. These regions showcase distinct environmental gradients and experience varying rates of environmental change influenced by global climatic shifts. Analysis revealed a diverse array of photosynthetic microorganisms, including Stramenopiles, Cyanobacteria, Rhizobiales, Burkholderiales, and photosynthetic purple sulfur Proteobacteria. Functional inference highlighted the high potential for carbohydrate, amino acid, and lipid metabolism in the Himalayan region, where organic carbon concentrations surpassed those in Antarctica by up to 2 orders of magnitude. Nitrogen cycling processes, including fixation, nitrification, and denitrification, are evident, with Antarctic cryoconite exhibiting a pronounced capacity for nitrogen fixation, potentially compensating for the limited nitrate concentrations in this region. Processes associated with the respiration of elemental sulfur and inorganic sulfur compounds such as sulfate, sulfite, thiosulfate, and sulfide suggest the presence of a complete sulfur cycle. The Himalayan region exhibits a higher potential for sulfur cycling, likely due to the abundant sulfate ions and sulfur-bearing minerals in this region. The capability for complete iron cycling through iron oxidation and reduction reactions was also predicted. Methanogenic archaea that produce methane during organic matter decomposition and methanotrophic bacteria that utilize methane as carbon and energy sources co-exist in the cryoconite, suggesting that these niches support the complete cycling of methane. Additionally, the presence of various microfauna suggests the existence of a complex food web. Collectively, these results indicate that cryoconite holes are self-sustaining ecosystems that drive elemental cycles on glaciers and potentially control carbon, nitrogen, sulfur, and iron exports downstream.

Functional antagonism and insights into the biosynthetic potential of human gut-derived microbes.

The specialised small molecules encoded by commensal microbes mediate distinct functional interactions. However, there is a landscape of antagonistic interactions mediated by specialised strains and their small molecules. Herein, the antagonistic landscape within a collection of 330 human gut-derived commensal microbial strains was elucidated to evaluate antimicrobial interactions as a defensive contributor, and gain new insights into structure-related functions. The potential antagonistic gut-derived strains displayed strain-specific selective inhibition. This is in contrast to common antimicrobial drugs, which typically wipe out a broad range of species and are usually found in environmental microbes. Genome sequencing of representative gut strains revealed the presence of significant biosynthetic gene clusters (BGCs) encoding compound families that contribute to antagonistic activities, and are important in host defence and maintaining gut homeostasis. Subsets of these BGCs were abundant in metagenomic sequencing data from healthy individuals. Furthermore, the cell culture secretome of these strains revealed potential biomarkers linked to hallmark pathways. These microorganisms have biosynthetic novelty and are a source of biologically significant natural products. Such natural products are essential in the development of new antimicrobial agents to reduce the usage of broad-spectrum antibiotics and combat antimicrobial resistance.

Pilot Study on Gut Microbiota Profile in Indian Children with Type 1 Diabetes.

Background: Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM). Objectives: To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control. Methodology: Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis. Results: The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria Blautia and Ruminococcus showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels (p < 0.05). Coprococcus and Propionibacterium were important negative predictors of glycaemic control (p < 0.05). Conclusion: Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like Ruminococcus and Blautia (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.

Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Hyperglycemic myocardial microenvironment significantly alters chromatin architecture and the transcriptome, resulting in aberrant activation of signaling pathways in a diabetic heart. Epigenetic marks play vital roles in transcriptional reprogramming during the development of DCM. The current study is aimed to profile genome-wide DNA (hydroxy)methylation patterns in the hearts of control and streptozotocin (STZ)-induced diabetic rats and decipher the effect of modulation of DNA methylation by alpha-ketoglutarate (AKG), a TET enzyme cofactor, on the progression of DCM. METHODS: Diabetes was induced in male adult Wistar rats with an intraperitoneal injection of STZ. Diabetic and vehicle control animals were randomly divided into groups with/without AKG treatment. Cardiac function was monitored by performing cardiac catheterization. Global methylation (5mC) and hydroxymethylation (5hmC) patterns were mapped in the Left ventricular tissue of control and diabetic rats with the help of an enrichment-based (h)MEDIP-sequencing technique by using antibodies specific for 5mC and 5hmC. Sequencing data were validated by performing (h)MEDIP-qPCR analysis at the gene-specific level, and gene expression was analyzed by qPCR. The mRNA and protein expression of enzymes involved in the DNA methylation and demethylation cycle were analyzed by qPCR and western blotting. Global 5mC and 5hmC levels were also assessed in high glucose-treated DNMT3B knockdown H9c2 cells. RESULTS: We found the increased expression of DNMT3B, MBD2, and MeCP2 with a concomitant accumulation of 5mC and 5hmC, specifically in gene body regions of diabetic rat hearts compared to the control. Calcium signaling was the most significantly affected pathway by cytosine modifications in the diabetic heart. Additionally, hypermethylated gene body regions were associated with Rap1, apelin, and phosphatidyl inositol signaling, while metabolic pathways were most affected by hyperhydroxymethylation. AKG supplementation in diabetic rats reversed aberrant methylation patterns and restored cardiac function. Hyperglycemia also increased 5mC and 5hmC levels in H9c2 cells, which was normalized by DNMT3B knockdown or AKG supplementation. CONCLUSION: This study demonstrates that reverting hyperglycemic damage to cardiac tissue might be possible by erasing adverse epigenetic signatures by supplementing epigenetic modulators such as AKG along with an existing antidiabetic treatment regimen.

Quorum sensing activities and genomic insights of plant growth-promoting rhizobacteria isolated from Assam tea.

Secretion of quorum sensing (QS) molecules is important for the effective colonization of host plants by plant growth-promoting rhizobacteria. The current study aims at the isolation and characterization of tea rhizo bacteria, which produce the QS molecules, acyl homoserine lactone (AHLs), along with multiple plant growth-promoting (PGP) activities. Thirty-one isolates were isolated from the tea rhizosphere, and screening for PGP activities resulted in the selection of isolates RTE1 and RTE4 with multiple PGP traits, inhibiting the growth of tea fungal pathogens. Both isolates also showed production of AHL molecules when screened using two biosensor strains, Chromobacterium violaceum CV026 and Escherichia coli MT 102(jb132). The isolates identified as Burkholderia cepacia RTE1 and Pseudomonas aeruginosa RTE4 based on genome-based analysis like phylogeny, dDDH, and fastANI calculation. Detailed characterization of AHLs produced by the isolates using reverse-phase TLC, fluorometry, and LC-MS indicated that the isolate RTE1 produced a short chain, C8, and a long chain C12 AHL, while RTE4 produced short-chain AHLs C4 and C6. Confocal microscopy revealed the formation of thick biofilm by RTE1 and RTE4 (18 and 23 µm, respectively). Additionally, we found several genes involved in QS, and PGP, inducing systemic resistance (ISR) activities such as lasI/R, qscR, pqq, pvd, aldH, acdS, phz, Sod, rml, and Pch, and biosynthetic gene clusters like N-acyl homoserine lactone synthase, terpenes, pyochelin, and pyocyanin. Based on the functional traits like PGP, biofilm formation and production of AHL molecules, and genetic potential of the isolates B. cepacia RTE1 and P. aeruginosa RTE4 appear promising candidates to improve the health and growth of tea plantations.

Strategizing the human microbiome for small molecules: Approaches and perspectives.

Studies of the human microbiome are providing a deeper understanding of its significance to human health, and increasing evidence links the microbiota with several diseases. Nevertheless, the exact mechanisms involved in human-microbe interactions are mostly undefined. The genomic potential of the human microbiome to biosynthesize distinct molecules outmatches its known chemical space, and small-molecule discovery in this context remains in its infancy. The profiling of microbiome-derived small molecules and their contextualization through cause-effect mechanistic studies may provide a better understanding of host-microbe interactions, guide new therapeutic interventions, and modulate microbiome-based therapies. This review describes the advances, approaches, and allied challenges in mining new microbial scaffolds from the human microbiome using genomic, microbe cultivation, and chemical analytic platforms. In the future, the complete biological characterization of a single microbe-derived molecule that has a specific therapeutic application could resolve the current limitations of microbiota-modulating therapies.

Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of Candida glabrata.

Expression of genome-wide alternative transcript isoforms and differential transcript isoform usage in different biological conditions (isoform switching) are responsible for the varied proteomic functional diversity in higher eukaryotic organisms. However, these mechanisms have not been studied in Candida glabrata, which is a potent eukaryotic opportunistic pathogen. Biofilm formation is an important virulence factor of C. glabrata that withstands antifungal drug stress and overcomes the host-immune response. Here, we present the genome-wide differential transcript isoform expression (DTE) and differential transcript isoform usage (DTU) in a mature biofilm growth phase of C. glabrata (clinical isolate; NCCPF 100,037) using the RNA sequencing approach. The DTE analysis generated 7837 transcript isoforms from the C. glabrata genome (5293 genes in total), and revealed that transcript isoforms generated from 292 genes showed significant DTU in the mature biofilm cells. Gene ontology, pathway analysis and protein-protein interactions of significant transcript isoforms, further substantiated that their specific expression and differential usage is required for transitioning the planktonic cells to biofilm in C. glabrata. The present study reported the possible role of expression of alternative transcript isoforms and differential transcript isoform usage in the mature biofilms of C. glabrata. The observation derived from the study may prove to be beneficial for making future antifungal therapeutic strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01036-7.

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures.

Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health's personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and >95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health.

MicFunPred: A conserved approach to predict functional profiles from 16S rRNA gene sequence data.

The 16S rRNA gene amplicon sequencing is a popular technique that provides accurate characterization of microbial taxonomic abundances but does not provide any functional information. Several tools are available to predict functional profiles based on 16S rRNA gene sequence data that use different genome databases and approaches. As variable regions of partially-sequenced 16S rRNA gene cannot resolve taxonomy accurately beyond the genus level, these tools may give inflated results. Here, we developed 'MicFunPred', which uses a novel approach to derive imputed metagenomes based on a set of core genes only, thereby minimizing false-positive predictions. On simulated datasets, MicFunPred showed the lowest False Positive Rate (FPR) with mean Spearman's correlation of 0.89 (SD = 0.03), while on seven real datasets the mean correlation was 0.75 (SD = 0.08). MicFunPred was found to be faster with low computational requirements and performed better or comparable when compared with other tools.

Gut, oral and skin microbiome of Indian patrilineal families reveal perceptible association with age.

The human microbiome plays a key role in maintaining host homeostasis and is influenced by age, geography, diet, and other factors. Traditionally, India has an established convention of extended family arrangements wherein three or more generations, bound by genetic relatedness, stay in the same household. In the present study, we have utilized this unique family arrangement to understand the association of age with the microbiome. We characterized stool, oral and skin microbiome of 54 healthy individuals from six joint families by 16S rRNA gene-based metagenomics. In total, 69 (1.03%), 293 (2.68%) and 190 (8.66%) differentially abundant OTUs were detected across three generations in the gut, skin and oral microbiome, respectively. Age-associated changes in the gut and oral microbiome of patrilineal families showed positive correlations in the abundance of phyla Proteobacteria and Fusobacteria, respectively. Genera Treponema and Fusobacterium showed a positive correlation with age while Granulicatella and Streptococcus showed a negative correlation with age in the oral microbiome. Members of genus Prevotella illustrated high abundance and prevalence as a core OTUs in the gut and oral microbiome. In conclusion, this study highlights that precise and perceptible association of age with microbiome can be drawn when other causal factors are kept constant.

Gut microbial diversity during pregnancy and early infancy: an exploratory study in the Indian population.

The gut microbial community is known to influence the human health and disease state and is shaped by various factors since birth. It is now evident that understanding the alterations in these commensal microbes during crucial stages of life is of utmost importance to determine and predict the health status of an individual. To study the gut microbiota in two such vital stages, pregnancy and infancy, we analyzed gut microbial communities from 20 mother-infant dyads at different stages of pregnancy and early infancy. In total, we analyzed 80 fecal samples for profiling the gut microbial community using 16S rRNA gene-based sequencing. We observed no significant alterations in the gut bacterial diversity during pregnancy; however, significant alterations were observed during the period from birth to six months in infants, with a reduction in Staphylococcus and Enterococcus and an increase in Bifidobacterium and Streptococcus with a more stable microbial community at the age of six months.