Aleksey A. Vatlin

The black soldier fly (Hermetia illucens L.) has emerged as a cornerstone technology for the circular economy, valorising organic waste into high-value insect protein and biofertiliser. The efficiency, safety, and adaptability of this bioconversion process are fundamentally dictated by the complex interplay between the insect host and its gut microbiome, which together function as an integrated ‘holobiont bioreactor’. This reactor is characterised by partially vertically transmitted core taxa and a dynamic, horizontally acquired microbial community. This review critically synthesises high-impact original research identified through a systematic literature search published predominantly between 2021 and 2026, incorporating foundational landmark studies, to provide a mechanistic overview of this holobiont’s function. We first dissect the architecture of the BSFL microbiome, examining the ‘nature vs. nurture’ debate of egg-associated vertical inheritance versus horizontal acquisition and highlighting the critical, yet often overlooked, role of the fungal mycobiome. We then explore the larval gut as a spatio-temporally compartmentalised bioreactor, where extreme physicochemical gradients and host–microbe metabolic crosstalk drive nutrient extraction and immunity. A central focus is placed on the ‘Bioremediation vs. Biosafety Paradox’, wherein the system’s capacity to degrade chemical xenobiotics and sanitise pathogens is contrasted with its propensity to amplify antimicrobial resistance genes (ARGs) and bioaccumulate contaminants like heavy metals and microplastics under specific substrate and exposure conditions. Finally, we evaluate the frontier of microbiome engineering from the deployment of native probiotics and synthetic microbial consortia (SynComs) to enhance performance to the use of prebiotics for mitigating ammonia emissions. This synthesis reveals that while BSFL technology holds immense promise, its industrial maturation is constrained by significant methodological limitations in the current literature. We conclude by advocating for a field-wide shift towards integrated multi-omics and viability-based analytical frameworks to ensure the development of safe, efficient, and regulatory-compliant bioconversion systems.

Atherosclerosis is a chronic immune–inflammatory disease of the arterial wall in which antigen-presenting cells (dendritic cells, macrophages and B cells) present locally generated antigens, such as oxidized low-density lipoprotein, to plaque-infiltrating T cells. Full T-cell activation requires costimulation through the B7 family ligands CD80 (B7-1) and CD86 (B7-2), which engage CD28 to activate T cells and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to restrain them. Although long considered functionally redundant, CD80 and CD86 are now known to be structurally and mechanistically distinct, differing in receptor affinity, susceptibility to CTLA-4-mediated trans-endocytosis, capacity to cis-heterodimerize with programmed death-ligand 1, and dependence relationships with regulatory versus effector T cells. In atherosclerosis, CD80 is expressed by lesional dendritic cells, macrophages, foam cells, B cells and, under inflammatory conditions, vascular endothelial and smooth muscle cells, with expression levels correlating with plaque vulnerability in humans. Genetic deletion, CTLA-4-Ig-based pharmacological blockade and selective small-molecule antagonism in preclinical models generally converge on a proatherogenic role for CD80/CD86-dependent costimulation, although combined genetic deletion of CD80 and CD86 has also been reported to paradoxically enhance early lesion formation in some contexts, while augmented CTLA-4-mediated coinhibition is atheroprotective—a balance corroborated by the accelerated atherosclerosis and cardiovascular toxicity observed with checkpoint-inhibitor cancer immunotherapy. Molecular imaging agents targeting CD80/CD86, repurposed CTLA-4-Ig biologics such as abatacept, and antigen-specific tolerogenic dendritic cell strategies together constitute an emerging translational pipeline. To our knowledge, this is the first review to integrate CD80’s structural and receptor pharmacology with its cellular sources in the plaque, preclinical genetic and pharmacological evidence, human plaque and biomarker data, molecular imaging approaches, and checkpoint inhibitor-associated cardiovascular toxicity within a single translational framework. This review synthesizes the structural biology, cellular sources, preclinical genetics, human plaque and biomarker data, and therapeutic and diagnostic implications of CD80 as an immune mediator and candidate therapeutic target in atherosclerosis.

Background/Objectives: Chronic metabolic inflammation is associated with pro-inflammatory macrophage activation and mitochondrial dysfunction. Semaglutide, a widely used GLP-1 receptor agonist, has been reported to possess systemic anti-inflammatory properties, but its action on human macrophages, especially in the context of mitochondrial regulation, remains poorly understood. The aim of the study was to evaluate the direct effect of semaglutide on macrophage polarization and to investigate the roles of cAMP signaling and mitochondrial regulation in this process. Methods: THP-1 and U-937 monocytic cell lines were differentiated into macrophages and polarized into the M1-like phenotype using LPS/IFN-γ. Cells were treated with 100 nM semaglutide in the presence or absence of the adenylyl cyclase inhibitor SQ22536. Intracellular cAMP levels, mRNA expression of macrophage markers and key regulators of mitochondrial biogenesis (SIRT1 and PGC-1α), and levels of pro- and anti-inflammatory cytokines were determined. The COX-1/SDH-A and mtDNA/nDNA ratios were analyzed as markers of mitochondrial biogenesis. Results: Semaglutide induced cAMP accumulation in M0- and M1-like macrophages derived from both cell lines. This response was significantly attenuated by GLP-1R antagonist exendin(9–39), supporting the presence of functional GLP-1R signaling. Semaglutide supplementation during inflammatory polarization resulted in reduced levels of pro-inflammatory markers (CD80/CD86, TNF-α, IL-6) and increased expression of M2-associated genes CD206 and CD163 and secretion of the anti-inflammatory cytokine IL-10. Semaglutide also increased SIRT1 and PGC-1α expression, the COX-1/SDH-A ratio, and the mtDNA/nDNA ratio, suggesting activation of processes associated with mitochondrial biogenesis. All of the effects of semaglutide described above were attenuated by SQ22536, supporting an important contribution of cAMP signaling to these responses. Conclusions: Semaglutide acts directly on human monocytic cell line-derived macrophages, attenuating the M1-like program and promoting a shift toward a less inflammatory phenotype. These effects strongly depend on cAMP signaling and are accompanied by increased expression of SIRT1 and PGC-1α and mitochondrial changes consistent with enhanced biogenesis.

Micro- and nanoplastics (MNPs) are emerging global pollutants that pose a significant threat to living organisms due to their widespread presence, ingestion by aquatic species, and ability to cross biological barriers, including the blood–brain barrier. Zebrafish is a well-established and convenient model for ecotoxicological research because of its small size, optical transparency, fully sequenced genome, high genetic homology to humans, ease of breeding, and short life cycle. Exposure to MNPs affects multiple organ systems in zebrafish, including the brain, eyes, liver, intestine, gills, and reproductive system. These particles can induce oxidative stress, inflammation, and interference with diverse biomolecules, leading to adverse biological effects. An analysis of transcriptomic alterations induced by MNPs exposure can contribute to understanding the mechanisms of these adverse effects. In this narrative review, we classify existing studies on MNPs exposure in zebrafish by affected organ system and summarize the gene expression-based evidence of MNP-induced toxicity with a particular focus on high-throughput approaches such as RNA sequencing and single-cell RNA sequencing.

The microbial degradation of petroleum hydrocarbons is a fundamental biogeochemical process and a cornerstone of environmental bioremediation. While traditional culture-based studies have outlined the basic principles, the advent of metagenomics has revolutionised our understanding by revealing the full genetic and functional diversity of hydrocarbon-degrading communities in situ. This review synthesises the current state of knowledge on both aerobic and anaerobic hydrocarbon biodegradation, providing a critical comparative analysis of traditional versus multi-omics methodologies. We provide an in-depth examination of aerobic mechanisms, initiated by oxygenases (e.g., alkB, PAH-RHDα), and contrast them with the diverse array of anaerobic activation pathways, including fumarate addition (bssA) and the recently elucidated direct carboxylation pathway for polycyclic aromatic hydrocarbons (PAHs). Furthermore, we highlight groundbreaking metagenomic insights into anaerobic benzene degradation and the critical role of syntrophic networks driven by interspecies electron transfer. Finally, we present specific case studies demonstrating the translation of genomic data into practical bioremediation strategies, such as the rational design of synthetic consortia. This review charts these recent advances, highlights remaining knowledge gaps, and outlines future directions for harnessing multi-omics to translate genomic potential into effective, field-scale environmental solutions.

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials.

Since there is no cure for Parkinson's disease yet, pharmacobiotic drugs based on the gut microbiota capable of producing the necessary pharmacologically active compo-nents are being developed. The drug LfU21 based on the strain of Limosilactobacillus fermentum U-21 is proposed as a candidate for pharmacobiotics in this work. To char-acterize the effectiveness of the studied drug, a combined LPS and lactacystin (LAC) induced PD model in the Wistar rat line was used. The analysis was performed using behavioral, biochemical, immune, and transcriptomic biomarkers. LfU21 reduces the level of α-synuclein, changes motor activity in the “Rung ladder” test and the expres-sion of the bdnf gene in both hemispheres of the brain. When exposed to LPS, LfU21 prevents changes in the level of the immune response, GSH, expression of the drd2 and bdnf genes, and the number of goblet cells in the intestine. When exposed to LAC and LAC+LPS, LfU21 prevents an increase in α-synuclein, a decrease in bdnf expression, and indicators in the “Open Field” and “Rung ladder” tests, respectively. The effect of LfU21 in a combined model of Parkinson's disease confirms its multifunctionality. This allows us to determine the cohort of patients for future clinical trials of LfU21.

Freshwater pollution is a global issue that can impact aquatic organisms in multiple ways. One of the many detrimental consequences of freshwater pollution is the disruption of the intestinal microbiome in aquatic animals. This review addresses the impact of various chemical entities like pesticides, heavy metals, antibiotics, dyes, and microplastic. Gut microbiota serves as a crucial regulator of metabolic processes across all organisms. Since numerous metabolic pathways are coordinated by microbial communities, even minor disruptions can lead to consequences ranging from mild to severe. The widespread use of chemicals in modern life has made them a primary focus of current gut microbiota research. Zebrafish (Danio rerio) can serve as a model organism to investigate gut microbiome responses to exposure to hazardous contaminants. In this review we include research studying pesticides (methomyl, λ-cyhalothrin, cyproconazole, dieldrin, penthiopyrad, acetochlor, metamifop, imidacloprid, difenoconazole, imazalil, cypermethrin), heavy metals (lead, cadmium, arsenic, chromium, copper, and various nanoparticles), antibiotics (oxytetracycline, florfenicol, doxycycline, trimethoprim, erythromycin, streptomycin, tetracycline, sulfamethoxazole, and clarithromycin), and microplastics (polystyrene, polyethylene, polyester, polypropylene). This review study provides a description of microbiome alterations due to single and combined short- and long-term exposure to the aforementioned contaminants in zebrafish and larvae microbiomes.

In 2022, the World Health Organization reported that tuberculosis (TB) was the second leading cause of death globally from a single infectious agent following COVID-19. The development of new antitubercular agents with novel mechanisms of action for use in complex TB therapy is considered a key approach to combating TB. In this study, we examined the gene expression profile of M. smegmatis when exposed to a promising antituberculosis agent, quinoxaline 1,4-dioxide (QdNO) 7-chloro-2-(ethoxycarbonyl)-3-methyl-6-(piperazin-1-yl)quinoxaline-1,4-dioxide-1 (LCTA-3368). We investigated how the bacterial response changed with different minimum inhibitory concentrations (MIC) (1/4 × MIC, 1/2 × MIC, and 1 × MIC) and durations (30 min and 90 min) of treatment with the drug. Our analysis revealed significant upregulation in genes involved in DNA repair and replication processes, as well as changes in the expression of 95 genes encoding proteins with oxidoreductase activity. We additionally showed that the concentration of reactive oxygen species increases in a dose-dependent manner upon exposure of M. smegmatis to LCTA-3368. These findings support the proposed mechanism of antibacterial action of QdNOs, which is associated with the formation of free radicals leading to DNA damage.

Soil health is a critical determinant of agricultural productivity and environmental sustainability. Traditional assessment methods often fail to provide a comprehensive understanding of soil microbial communities and their functions. This study addresses this challenge by employing metagenomic techniques to assess the functionality of soil microbiomes in Russian black soil, renowned for its high fertility. We utilized shotgun metagenomic sequencing to analyze soil samples from Western Siberia subjected to different degrees of agro-soil disturbance. We identified functional genes involved in carbon (accA, argG, acsA, mphE, miaB), phosphorus (phoB, ppa, pstB, pnp, phnJ), and nitrogen (queC, amiF, pyrG, guaA, guaB, napA) metabolic pathways and associated with changes in microbial diversity, in general, and higher representation of certain bacterial species—Bradyrhizobium spp. The results demonstrated significant differences in microbial composition and functional potential between tillage treatments. No-Till technology and conventional tillage practices promoted beneficial microbial communities and enhanced soil health compared to long-term fallow soil. This work underscores the potential of metagenomic analysis in providing a comprehensive understanding of soil health, marking a significant advancement in the field.