The gut microbiota produces a variety of metabolites that are crucial for regulating host health and physiological homeostasis. Indole-3-acetic acid (IAA), a microbial metabolite of tryptophan, exhibits diverse biological activities including anti-inflammatory, anti-tumor, anti-obesity, hepatoprotective, enteroprotective, and neuromodulatory effects. Accumulating evidence has demonstrated its therapeutic potential against metabolic, inflammatory, and neurological disorders. Emerging evidence suggests that IAA exerts beneficial effects on mammalian health through multiple mechanisms, including modulation of gut microbiota composition, enhancement of intestinal barrier integrity, immune regulation, attenuation of bone loss, and improvement of glucose and lipid homeostasis. This review systematically summarizes current knowledge regarding IAA sources, elucidates recent advances in understanding its biological functions, and integrates existing evidence on its mechanisms of action in mammalian systems. Collectively, this synthesis provides a framework for future investigations and translational applications of IAA.

Almost all bacteria have peptidoglycan (PG) components that are essential for virulence and are absent in humans, making them a top-priority target for antibiotics and vaccines. The rise of multidrug-resistant bacteria (MRB) necessitates urgent expansion of our arsenal of inhibitors targeting the PG cell wall. This review addresses our understanding of PG biosynthesis and recycling processes, emphasizing the need to identify novel target proteins and redesign existing PG-targeted antimicrobial peptides. Building on our understanding of cell wall biochemistry and biogenesis derived from Escherichia coli, we also aim to compare and elucidate the cell wall processes in other pathogens, such as Acinetobacter baumannii and Salmonella Typhimurium, where knowledge remains incomplete. We cover in detail the distinct roles of PG-related proteins in Gram-negative bacteria, strategies to block PG biosynthesis/recycling pathways, and their potential as novel antibiotic targets to address the growing challenge of antibiotic resistance. Finally, we review the application of rigorous immuno-informatics analysis and several immune filters to construct epitope-specific vaccines displaying PG-related proteins on the surface of outer membrane vesicles (OMVs), aiming to combat MRB proliferation.

Candida albicans is a primary pathogen implicated in invasive fungal infections. Through its intricate iron uptake and regulatory systems, C. albicans adeptly adapts to various iron-rich environments, circumventing the growth and virulence restrictions imposed by the host’s nutritional immunity and intensifying infection severity. This fungus activates the Sef1-Sfu1-Hap43 iron homeostasis regulatory circuit via iron bioavailability sensors (iron-sulfur cluster assembly system). This activation precisely regulates multiple iron uptake pathways, including the high-affinity iron reduction system, heme-iron uptake pathway, and siderophore uptake system, as well as genes involved in iron utilization and storage, thus ensuring effective iron acquisition and maintaining iron homeostasis across diverse environmental conditions and developmental stages. Conversely, disruptions in iron metabolism markedly diminish C. albicans’s pathogenic potential by impairing mitochondrial function, suppressing hyphal formation, limiting fungal colonization, and reversing antifungal drug resistance. This review presents a comprehensive analysis of the mechanisms governing iron uptake and regulation in C. albicans and examines the consequences of impaired iron homeostasis on mitochondrial function, hyphal formation, infection progression, and drug resistance. Our goal is to provide a theoretical framework to better understand the pathogenesis of C. albicans and to support the development of targeted therapeutic strategies against this resilient pathogen.

The interactions between viruses and protists have been crucially impacting the ecosystem. In recent studies, it has been found that the protists are not only able to consume, ingest or inactivate a variety of viruses, resulting in a reduction of the viral load, but instead, they can treat viruses as the exclusive source of nutrients, exhibiting “Virovory” (virus-only diet). These small protists can act as virosomes (organisms harnessing nutrients from the viruses) and utilize the viruses as the only source of nourishment, implying the protist to multiply and grow. The viral reduction was previously thought to be only because of the action of abiotic factors (temperature, ultraviolet light, chemicals, membrane adsorption, etc.). However, virovory suggests that organic material flow in microbial communities, the impact of viruses on the food web and, the role of protists in regulating viral populations are crucial factors in ecosystem dynamics. In this review, ingestion, digestion, and inactivation of a variety of viruses by protists are discussed. Several questions can be answered by further research on understanding the mechanisms behind the inactivation of viruses, the impact of reduced viral load on other microbial populations, and the large-scale employability of these little protists in removing pathogenic viruses from the environment.

This review discusses the chemical properties, synthesis and detection, and biological functions of a molecular group of cis-2-unsaturated fatty acids, containing fatty acid carbon chains of various lengths and cis double-bond configurations, known as the diffusible signaling factor family (DSFF). Early postulation of the conserved nature of the DSFF among Gram-negative bacteria have now been challenged by the latest evidences that unraveled their presence in a various other distinct microorganisms. Over the last decade, a significant depth and breadth of understanding has been made on the multifaceted functions of DSFFs among bacteria, and their interactions with evolutionarily divergent fungi, plants insects and small animals. While the knowledge of the chemical nature and functions of DSFF within microbial systems is still developing, DSFF molecules such as BDSF, DSF, and SDSF have been found to modulate microbial virulence, cell adhesion, biofilm formation and dispersion, cell motility, and antimicrobial tolerance. Given their capacity to influence microbial ecosystems and the rapid emergence of novel DSFF-like molecules, it is critical to identify the full spectrum of DSFF members and to better understand the functions of this complex messenger system as they offer significant potential to be exploited in the development of new therapeutic strategies to combat the rising global healthcare threat of antimicrobial resistance. This narrative review therefore provides a broad picture of the DSFF quorum sensing with a core foundation built from seminal literature while highlighting the latest developments in the field.

Candida infections, particularly invasive candidiasis, pose a serious global health threat. Candida albicans is the most prevalent species causing candidiasis, and resistance to key antifungal drugs, such as azoles, echinocandins, polyenes, and fluoropyrimidines, has emerged. This growing multidrug resistance (MDR) complicates treatment options, highlighting the need for novel therapeutic approaches. Antifungal peptides (AFPs) are gaining recognition for their potential as new antifungal agents due to their diverse structures and functions. These natural or recombinant peptides can effectively target fungal virulence and viability, making them promising candidates for future antifungal development. This review examines infections caused by Candida species, the limitations of current antifungal treatments, and the therapeutic potential of AFPs. It emphasizes the importance of identifying novel AFP targets and their production for advancing treatment strategies. By discussing the therapeutic development of AFPs, the review aims to draw researchers’ attention to this promising field. The integration of knowledge about AFPs could pave the way for novel antifungal agents with broad-spectrum activity, reduced toxicity, targeted action, and mechanisms that limit resistance in pathogenic fungi, offering significant advancements in antifungal therapeutics.

Dental caries, as a biofilm-related disease, is closely linked to dysbiosis in microbial ecology within dental biofilms. Beyond its impact on oral health, bacteria within the oral cavity pose systemic health risks by potentially entering the bloodstream, thereby increasing susceptibility to bacterial endocarditis, among other related diseases. Streptococcus mutans, a principal cariogenic bacterium, possesses virulence factors crucial to the pathogenesis of dental caries. Its ability to adhere to tooth surfaces, produce glucans for biofilm formation, and metabolize sugars into lactic acid contributes to enamel demineralization and the initiation of carious lesions. Its aciduricity and ability to produce bacteriocins enable a competitive advantage, allowing it to thrive in acidic environments and dominate in changing oral microenvironments. In contrast, commensal streptococci, such as Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, act as primary colonizers and compete with S. mutans for adherence sites and nutrients during biofilm formation. This competition involves the production of alkali, peroxides, and antibacterial substances, thereby inhibiting S. mutans growth and maintaining microbial balance. This dynamic interaction influences the balance of oral microbiota, with disruptions leading to shifts in microbial composition that are marked by rapid increases in S. mutans abundance, contributing to the onset of dental caries. Thus, understanding the dynamic interactions between commensal and pathogenic bacteria in oral microecology is important for developing effective strategies to promote oral health and prevent dental caries. This review highlights the roles and competitive interactions of commensal bacteria and S. mutans in oral microecology, emphasizing the importance of maintaining oral microbial balance for health, and discusses the pathological implications of perturbations in this balance.

Candida albicans stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of C. albicans, alcohol dehydrogenase 1 (Adh1) is one of the important enzymes that converts acetaldehyde produced by pyruvate decarboxylation into ethanol at the end of glycolysis. Leveraging the foundational processes of alcoholic fermentation, Adh1 plays an active role in multiple biological phenomena, including biofilm formation, interactions between different species, the development of drug resistance, and the potential initiation of gastrointestinal cancer. Additionally, Adh1 within C. albicans has demonstrated associations with regulating the cell cycle, stress responses, and various intracellular states. Furthermore, Adh1 is extracellularly localized on the cell wall surface, where it plays roles in processes such as tissue invasion and host immune responses. Drawing from an analysis of ADH1 gene structure, expression patterns, and fundamental functions, this review elucidates the intricate connections between Adh1 and various biological processes within C. albicans, underscoring its potential implications for the prevention, diagnosis, and treatment of candidiasis.

Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.

Bile acids (BAs) are an important metabolite produced by cholesterol catabolism. It serves important roles in glucose and lipid metabolism and host-microbe interaction. Recent research has shown that different gut-microbiota can secrete different metabolic-enzymes to mediate the deconjugation, dehydroxylation and epimerization of BAs. In addition, microbes mediate BAs transformation and exert physiological functions in metabolic diseases may have a potentially close relationship with diet. Therefore, elaborating the pathways by which gut microbes mediate the transformation of BAs through enzymatic reactions involved are principal to understand the mechanism of effects between dietary patterns, gut microbes and BAs, and to provide theoretical knowledge for the development of functional foods to regulate metabolic diseases. In the present review, we summarized works on the physiological function of BAs, as well as the classification and composition of BAs in different animal models and its organs. In addition, we mainly focus on the bidirectional interactions of gut microbes with BAs transformation, and discuss the effects of diet on microbial transformation of BAs. Finally, we raised the question of further in-depth investigation of the food-gut microbial-BAs relationship, which might contribute to the improvement of metabolic diseases through dietary interventions in the future.