Rina Rani Ray

Biofilm is a three-dimensional structural assemblage of Gram-positive and Gram-negative bacteria which forms multiple layers on both living and non-living surfaces, including various organs, tissues, and medical equipment. The human body is an ideal site for the accumulation of trillions of microbiomes, of which many are potentially able to form multiple layers of biofilm, along with extracellular polymeric substances (EPS), autoinducing peptides production through the quorum-sensing regulatory mechanism. The anatomy of the human body is much more complex due to the presence of several functioning systems and secretions. Hormones are the secretions from endocrine glands, that influence various biochemical processes within the body. Sex steroids or sex hormones are special steroids differing based on gender, and have a series of functional beneficiaries on the reproductive system. Recent studies unveil some of the correlation of sex hormones with the composition of the human microbiome, which has gained significant attention as reproductive diseases are growing and becoming increasingly unavoidable across the globe. In this chapter we will discuss the impact of human sex steroids over bacterial growth, functions, and pathogenicity. This will provide a clear knowledge of the mechanism of biofilm formation and the influences of sex hormones to make it stronger and antibiotic-resistant.

Catecholamines are the derivatives of tyrosine and these hormones include epinephrine (E), norepinephrine (NE), and dopamine, all of which play crucial roles both as hormones and neurotransmitters. Their role is to prepare the body to combat stress situations with fright, fight and flight responses. The catecholamines, as such, are found to encourage the biofilm formation in both Gram-positive and Gram-negative bacteria and also in fungus like Candida sp. Catecholamines are found to induce biofilm formation in several pathogenic bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus neumoniae, and, Micrococcus luteus, and enteric bacteria such as Campylobacter jejuni, Listeria monocytogenes, and Aeromonas hydrophila. Due to these biofilm-promoting activities, regular contact with these hormones brings about the damage of implants. Despite the lack of any antibiofilm properties of catecholamines, their structural resemblance to quorum-sensing molecules often enables them to participate in ferrous-assisted in situ polymerization, leading to the breakdown of the biofilm matrix and the destruction of the biofilm. Due to an overall biofilm-promoting tendency, the prolonged intake of these hormones as drugs may cause the damage of prosthetics and implants by encouraging biofilm growth.

Bacteria use quorum sensing (QS), a high-level signaling process employing autoinducer (AI) molecules, to control virulence, biofilm formation, and population-level behaviors. The process is crucial for both Gram-positive and Gram-negative bacteria, affecting their capacity to thrive in diverse environments. In addition, host-derived stress hormones play important roles in the pathogenicity of bacteria through enhanced growth, virulence, and immune evasion. Catecholamines act as siderophores that assist in the acquisition of iron and increase bacterial resistance. QS in Gram-negative bacteria is mediated by acyl-homoserine lactones that trigger synchronized gene expression at elevated cell density. In contrast, Gram-positive bacteria utilize a peptide-based signaling system for similar regulatory purposes. The disruption of QS by quorum-quenching mechanisms like enzymatic degradation of AI molecules, receptor antagonists, or the inhibition of gene activation are very promising avenues for controlling bacterial infections and antimicrobial resistance. Additionally, bacterial QS systems interact with host endocrine signaling, enabling pathogens to exploit stress-induced hormonal alterations for survival. This cross-kingdom communication underscores the need for targeted interventions, interfering with bacterial signaling without disrupting host–microbe homeostasis. It is critical to comprehend QS-host-derived hormone complex interaction in order to innovate novel anti-microbial strategies, particularly in the healthcare and aquaculture sectors, where bacterial infection poses a critical threat.

The formation of biofilms in the human body largely relies on catecholamines, including norepinephrine and epinephrine. Biofilms are complex aggregations of microorganisms that adhere to surfaces and are enclosed within protective extracellular matrices that enhance their resistance to immune responses and antibiotic therapies. Studies indicate that stress hormones increase the growth and virulence of pathogenic bacteria mainly the ESKAPE pathogens, thereby helping in biofilm formation. The hormones raise bacterial adhesions, enhance quorum sensing, and increase the production of an extracellular matrix by which they easily form biofilms on medical devices, wounds, and tissues. The increase in these hormones under stress then opens up environments promoting the strength and the durability of biofilms. It makes interventions for infections caused by implants and chronic wounds challenging. The linkage of the stress hormone with the development of biofilm may point to stress management and understanding biochemical interactions with microbial behaviour as trends that can lead to the discovery of new therapeutic interventions for treating and preventing infections through the process of biofilm. Here, in this chapter, light has been thrown on how the stress hormones can impact biofilm formation in human bodies.

Enteric hormones ensure digestive workflow and nutrient uptake and help regulate the host system for biological sustenance. This homeostasis involves several enteroendocrine cells, the host’s gastrointestinal tract, the overall neurological network, and an adaptive self-functioning entity—the biofilms. The chapter sheds light on some of the major enteric hormones, their physiological functions and factors, an overview of the role, development, and impact of biofilms, and the bidirectional relationship between enteric hormones and biofilms. These hormones play a vital role in modulating the host environment, which, in turn, can have either a beneficial or a derogatory impact on the growth, formation, development, niche, and virulence of host biofilms. Further, the impact of biofilms on the release, nature, and extent of enteric hormones is also highlighted, showcasing a bidirectional cross-talk between the two key players of gastrointestinal health. The chapter also demonstrates that different host and biofilm-specific factors like diet, gender, and gut–brain cross-talk and their clinical relevance can affect the bidirectional enteric hormone–host biofilm dialogue. In addition, a few key loci of interventions in the domain of enteric hormone–biofilm developments have been emphasized to urge pioneering researchers to evaluate the underlying mechanisms for crafting potent therapeutic strategies for personalized health care and diverse populations.

The interplay between the sugar-regulating hormones and the formation of biofilms has gained interest in recent decades. Hormones such as glucagon, insulin, epinephrine, cortisol and growth hormone (GH) aid in the modulation of biofilm formation by microbes. These hormones are primarily known for the maintenance of homoeostasis among humans, but they may also take part in influencing microbial pathogenesis and bacterial accumulation. This chapter deals with the way in which the levels of hormonal fluctuations, mainly in metabolic diseases like diabetes mellitus, can affect the development of biofilms, the expression of virulence factors, and the regulation of quorum sensing (QS) in bacterial cells. This chapter also refers to the change in microbiome that occurs due to the modification of hormonal levels within the human body. The conjunction of microbiology with endocrinology may open up new avenues for the study of the host–microbe interactions in another dimension, thereby developing interdisciplinary approaches for management of biofilm-associated infections among humans.

Biofilm, being a conglomeration of a microbial community, is composed of various sessile forms of microbes coexisting peacefully surrounded by an extracellular polymeric substances (EPS) matrix. The normal microbiota exists as structured communities experiencing a regular episode of changes throughout the life of the host. The insight of biofilm dynamics includes both vertical and horizontal growth, of which the former clearly shows a “biphasic growth” with an increase in the vertical growth rate; this is then followed by a linear decrease. This involves various factors, such as change in environment and lifestyle, infections and diseases and hydrodynamic factors. Such dynamicity is visible in the major ecosystems of human body, namely the oral, gut, skin, and vaginal microbiomes. A few factors regulating such changes, like hormones, quorum sensing, c-di-GMP signalling, small non-coding RNAs (sRNAs), and environmental cues, confer regular change in biofilm and thereby induce adaptability.