Microbiota and epigenetics: Health impact.

Epigenetic changes associated with disease development and progressions are of increasing importance because of their potential diagnostic and therapeutic applications. Several epigenetic changes associated with chronic metabolic disorders have been studied in various diseases. Epigenetic changes are mostly modulated by environmental factors, including the human microbiota living in different parts of our bodies. The microbial structural components and the microbially derived metabolites directly interact with host cells, thereby maintaining homeostasis. Microbiome dysbiosis, on the other hand, is known to produce elevated levels of disease-linked metabolites, which may directly affect a host metabolic pathway or induce epigenetic changes that can lead to disease development. Despite their important role in host physiology and signal transduction, there has been little research into the mechanics and pathways associated with epigenetic modifications. This chapter focuses on the relationship between microbes and their epigenetic effects in diseased pathology, as well as on the regulation and metabolism of the dietary options available to the microbes. Furthermore, this chapter also provides a prospective link between these two important phenomena, termed "Microbiome and Epigenetics."

Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens.

Antibiotics, which hit the market with astounding impact, were once called miracle drugs, as these were considered the ultimate cure for infectious diseases in the mid-20th century. However, today, nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperiling the foundation of modern medicine. During the COVID-19 pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance (AMR). Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against multidrug-resistant (MDR) pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.

Structure, functions, and diversity of the healthy human microbiome.

Taxonomic composition and functional potency of microbes associated with different parts of the human body have largely been explored by culture-independent metagenome sequencing. The diverse microbiota living throughout the human body is made up of thousands of microbial taxa from all three domains of life: Archaea, Bacteria, and Eukarya. Microbial load and functional potency in different body sites are well distinct and have minimal resemblance at higher taxonomic levels between the two habitats. The highest microbial load, diversity, and functional potency including biosynthesis of essential nutrients, chemical modifications of dietary components, and sources of immunomodulatory molecules, are found in the gut microbiome. However, the inter-individual diversity and dynamics of the human microbiome in a given body habitat vary greatly over time. Both environmental factors and host genetics contribute significantly to shaping microbial community structure and its stability. A basic understanding of native microbial compositions and their functional potency and stability in different parts of healthy humans living across geography will help us to identify disease-specific microbiota and develop potential microbiome-based therapeutics. Here, we updated our current understanding of the diversity, dynamics, and functional potency of microbiomes associated with different parts of the human body.

Vaginal microbiome dysbiosis in preterm birth.

All the environmentally exposed surfaces of the human body harbor ecologically distinct microbial communities with a mutualistic beneficial relationship. Depending on the body sites, microbes may provide metabolic functions, protection against pathogens, and signaling molecules to modulate host physiology and reduce disease susceptibility. Our recent understanding of the vaginal microbiome based on culture-independent 16S rRNA gene sequencing indicates that Lactobacillus-dominated microbial communities of healthy women play an important role in decreasing susceptibility to several urogenital diseases, including bacterial, fungal and viral infections. The findings of shotgun sequencing of the vaginal microbiome suggest that microbial-derived lactic acid, bacteriostatic, bactericidal molecules, and lower vaginal pH mediate such protections and regulations. Bacterial species, the dominant component of the vaginal microbiome, also play a key role in determining the gestation period and birth outcomes of reproductive-age women. The presence of Lactobacillus crispatus species in the vaginal milieu reduces the risk of preterm delivery in women of Asian ancestry. A deeper knowledge of the vaginal microbiota's role in the succession and development of newborn gut bacteria would also be beneficial. The microbiome of the mother changes throughout pregnancy and is linked to the microbiome of the newborn. This chapter highlights updated information and new opportunities for human microbiome research, focusing on the assessment of the risk of preterm birth.