From big data and experimental models to clinical trials: Iterative strategies in microbiome research

Cell, Journal Year: 2025, Volume and Issue: 188(5), P. 1178 - 1197

Published: March 1, 2025

Microbiome research has expanded significantly in the last two decades, yet translating findings into clinical applications remains challenging. This perspective discusses persistent issue of correlational studies microbiome and proposes an iterative method leveraging silico, vitro, ex vivo, vivo toward successful preclinical trials. The evolution methodologies, including shift from small cohort to large-scale, multi-cohort, even "meta-cohort" analyses, been facilitated by advancements sequencing technologies, providing researchers with tools examine multiple health phenotypes within a single study. integration multi-omics approaches-such as metagenomics, metatranscriptomics, metaproteomics, metabolomics-provides comprehensive understanding host-microbe interactions serves robust hypothesis generator for downstream vitro research. These hypotheses must then be rigorously tested, first proof-of-concept experiments clarify causative effects microbiota, goal deep mechanistic understanding. Only following these phases can conducted translation clinic. We highlight importance combining traditional microbiological techniques big-data approaches, underscoring necessity diverse model systems enhance translational potential

Language: Английский

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Lysosomal cationic proteins as the basis of cellular and humoral immunity of animals: the role of neutrophil extracellular traps (NETs) in immune homeostasis (review)

Agrarian science, Journal Year: 2025, Volume and Issue: 1(1), P. 57 - 70

Published: Jan. 28, 2025

Relevance. Lysosomal cationic proteins (LCP) of granulocytic leukocytes: elastase, cathepsin G, proteinase-3, calgranulin, cathelicidins, defensins, lactoferrin, protegrins are active against viruses, bacteria, fungi, protozoa. The issues physiological regulatory, immune and pathological effects LCP their derivatives – neutrophil (heterophil) extracellular traps (NETs) on pathogens, healthy cellular tissue structures the body noted. Results. increment granulocytes is realized by: 1. merocrine type — by degranulation; 2. exocytosis false degranulation, that is, process decationization lysosomes containing granules with apocrine or holocrine secretion. Decationization implements LCP, extrusion intact from cell diffusion through lysosome membrane. Lysosome degranulation reactions form phagolysosomes initiate phagocytosis, ensure formation functions NETs. NETs formed non-lytic (non-lytic) lytic (lyzed) pathways in septic aseptic inflammation, ontogenetic development links. stereotypically intravascular during oxidative stress a regime, when stimulated products metabolism. Using cytochemical test highly sensitive acid-base bromophenol blue indicator, subcellular manifestations age-related activity accumulated granulocyte were studied avian model organism (Aves), nonspecific adaptive (NAR) vertebrates early postnatal ontogenesis studied. basis for NAR relationship groups leukocytes (lymphocytes, monocytes granulocytes) dynamics lysosomal proteins. method calculating level potential capabilities phagocytic .NETs includes indices characterizing directions intensity granulocytes, taking into account processes: initiation link; involved implementation humoral link immunity.

Language: Английский

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Stem cell-specific NF-kB is required for stem cell survival and epithelial regeneration upon intestinal damage.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT Immune signals coordinate the repair of damaged epithelia by intestinal stem cells. However, it is unclear if immune pathways act autonomously within cell to direct damage response pathway. We consider this an important question, as dynamics are essential for formation and maintenance entire epithelium. used Drosophila determine impact cell-specific loss NF-κB on tissue regeneration upon chemical injury. found that enhanced death, impaired enterocyte renewal increased mortality. Mechanistically, we showed inhibition apoptosis NF-κB-dependent viability repair. Combined, our data demonstrate cell-intrinsic activity orderly epithelia.

Language: Английский

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Drosophila symbionts in infection: when a friend becomes an enemy

Infection and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The insect microbiome is comprised of extracellular microbial communities that colonize the host surfaces and endosymbionts reside inside cells tissues. Both these participate in essential aspects biology, including immune response interactions with pathogens. In recent years, our knowledge about role infection has increased tremendously. While many studies have highlighted microbiome's protective effect against various natural enemies insects, unexpected discoveries shown some members microbiota can facilitate pathogenic infections. Here, we summarize fruit fly, Drosophila melanogaster, substantially progressed understanding host-pathogen-microbiome during infection. We on mechanisms gut microbiota, highlight examples exploitation by pathogens, detail endosymbiont-mediated protection. addition, delve into a previously neglected topic research-the crosstalk between microbiota. Finally, address how remain resilient to responses stably By examining influenced reciprocally affects outcomes, this review provides timely cohesive coverage roles

Language: Английский

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Varying phylogenetic signal in susceptibility to four bacterial pathogens across species of Drosophilidae

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2025, Volume and Issue: 292(2045)

Published: April 1, 2025

Bacterial infections are a major threat to public health. Pathogen host shifts—where pathogen jumps from one species another—are important sources of emerging infectious diseases. However, compared with viruses, we know relatively little about the factors that determine whether bacteria can infect novel host, such as how phylogenetics constrains variation in range and link between phylogeny infectivity virulence pathogen. Here, experimentally examined susceptibility bacterial using panel 36 Drosophilidae four pathogens ( Providencia rettgeri , Pseudomonas entomophila Enterococcus faecalis Staphylococcus aureus ). The outcomes infection differed greatly among across species. explains considerable amount susceptibility, greatest phylogenetic signal for P. infection, explaining 94% mortality. Positive correlations were observed mortality load three out pathogens. Correlations positive but largely non-significant, suggesting is mostly pathogen-specific. These results suggest may be predicted by phylogeny, effect vary magnitude different bacteria.

Language: Английский

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Celebrating the fifth edition of the International Symposium on Fungal Stress – ISFUS, a decade after its 2014 debut

Fungal Biology, Journal Year: 2025, Volume and Issue: unknown, P. 101590 - 101590

Published: May 1, 2025

Language: Английский

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Massively parallel mutant selection identifies genetic determinants of Pseudomonas aeruginosa colonization of Drosophila melanogaster

mSystems, Journal Year: 2024, Volume and Issue: 9(3)

Published: Feb. 21, 2024

is recognized for its ability to colonize diverse habitats and cause disease in a variety of hosts, including plants, invertebrates, mammals. Understanding how this bacterium able occupy wide-ranging niches important deciphering ecology. We used transposon sequencing [Tn-Seq, also known as insertion (INSeq)] identify genes

Language: Английский

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Environment and diet shape the geography-specificDrosophila melanogastermicrobiota composition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

ABSTRACT Geographic and environmental variation in the animal microbiota can be directly linked to evolution wild fitness of their hosts but often appears disordered. Here, we sought better understand patterns that underlie composition Drosophila melanogaster . First, temperature predicted geographic fly microbial communities than latitude did. The also differed between flies diets, supporting previous conclusions is not merely a reflection diet. Flies feeding on different diets varied significantly composition, sampled from individual apples were exceptionally depauperate for Lactic Acid Bacteria (LAB), major bacterial group laboratory flies. However, bore more LAB when other fruits or compost piles. Follow-up analyses revealed abundance uniquely responds fruit decomposition, whereas members indicate temporal seasonal progression. Finally, show diet-dependent associated with phenotypic differentiation lines collected single orchard. These last findings link covariation flies’ dietary history, genetic across relatively small (single-orchard) landscapes, reinforcing critical role environment-dependent play local adaptation genomic model host. SIGNIFICANCE STATEMENT animals influence hosts’ fitness, it hard predict explain how varies animals. describe ordered by temperature, humidity, distance, diet type. We these determinants help lactic acid bacteria (LAB) flies, including rarity some studies. phenotypes segregate illuminating links host evolution. Together, compositions shape an animal’s life history.

Language: Английский

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Common soluble carbohydrates affect the growth, survival, and fatty acid profile of black soldier fly larvae Hermetia illucens (Stratiomyidae)

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 15, 2024

The black soldier fly, Hermetia illucens (L. 1758), is an omnivorous saprophagous insect with a high potential for valorizing organic by-products rich in carbohydrates. Among carbohydrates, H. relies on soluble sugars the growth and storage lipid synthesis. This study aimed to assess impact of common development, survival, fatty acid composition illucens. Monosaccharides disaccharides were individually incorporated into chicken feed diet. Cellulose was used as control. Larvae fed glucose, fructose, sucrose, maltose grew faster than control larvae. In contrast, lactose exhibited anti-nutritional effects larvae, slowing down reducing final individual weight. However, all produced larvae fatter Notably, tested shaped profile. Maltose sucrose increased saturated content compared cellulose. Conversely, bioaccumulation dietary unsaturated acids. first demonstrate effect profile Our findings highlight that carbohydrates have significant fly can thus determine their applications.

Language: Английский

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Whole-genome sequences of two Drosophila melanogaster microbiome symbionts

Microbiology Resource Announcements, Journal Year: 2023, Volume and Issue: 12(11)

Published: Oct. 13, 2023

and

Language: Английский

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