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.

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.

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 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.