The mycobiome in human cancer: analytical challenges, molecular mechanisms, and therapeutic implications

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 15, 2025

The polymorphic microbiome is considered a new hallmark of cancer. Advances in High-Throughput Sequencing have fostered rapid developments research. interaction between cancer cells, immune and microbiota defined as the immuno-oncology (IOM) axis. Fungal microbes (the mycobiome), although representing only ∼ 0.1-1% microbiome, are critical immunologically active component tumor microbiome. Accumulating evidence suggests possible involvement commensal pathogenic fungi initiation, progression, treatment responsiveness. tumor-associated mycobiome mainly consists gut mycobiome, oral intratumoral mycobiome. However, role remains poorly understood, diversity complexity analytical methods make it challenging to access this field. This review aims elucidate causal complicit roles development progression while highlighting issues that need be addressed executing such We systematically summarize advantages limitations current fungal detection analysis methods. enumerate integrate these recent findings into our understanding accompanied by prospect novel exhilarating clinical implications.

Язык: Английский

---

Microbiome Stability Is Linked to Acropora Coral Thermotolerance in Northwestern Philippines

Environmental Microbiology, Год журнала: 2025, Номер 27(2)

Опубликована: Янв. 31, 2025

Corals associate with a diverse community of prokaryotic symbionts that provide nutrition, antioxidants and other protective compounds to their host. However, the influence microbes on coral thermotolerance remains understudied. Here, we examined microbial communities associated colonies Acropora cf. tenuis exhibit high or low upon exposure 33°C (heated) relative 29°C (control). Using 16S rRNA sequencing, show structure all A. was similar each at control temperature. Thermotolerant colonies, however, had relatively greater abundance Endozoicomonas, Arcobacter, Bifidobacterium Lactobacillus. At elevated temperature, only thermosensitive showed distinct shift in microbiome, an increase Flavobacteriales, Rhodobacteraceae Vibrio, accompanying marked bleaching response. Functional prediction indicated thermotolerant corals were enriched for genes related metabolism, while microbiomes cell motility antibiotic compound synthesis. These differences may contribute variable performance under thermal stress. Identification taxa correlated provides insights into beneficial bacterial groups could be used microbiome engineering support reef health changing climate.

Язык: Английский

---

Linking dietary fiber to human malady through cumulative profiling of microbiota disturbance

iMeta, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Abstract Dietary fiber influences the composition and metabolic activity of microbial communities, impacting disease development. Current understanding intricate fiber‐microbe‐disease tripartite relationship remains fragmented elusive, urging a systematic investigation. Here, we focused on microbiota disturbance as robust index to mitigate various confounding factors developed Bio‐taxonomic Hierarchy Weighted Aggregation (BHWA) algorithm integrate multi‐taxonomy data, thereby illuminating complex relationships among dietary fiber, microbiota, disease. By leveraging similarities, (1) classified 32 types fibers into six functional subgroups, revealing correlations with solubility; (2) established associations 161 diseases, uncovering shared patterns that explain co‐occurrence (e.g., type II diabetes kidney diseases) distinct discern symptomatically similar diseases inflammatory bowel irritable syndrome); (3) designed body‐site‐specific scoring scheme, computing score ( DS ) for each highlighting pronounced capacity Crohn's disturb gut = 14.01) in contrast food allergy's minimal 0.74); (4) identified 1659 fiber‐disease associations, predicting potential modulate specific changes associated interest; (5) murine models validate preventive therapeutic effects arabinoxylan notably perturbed Bacteroidetes Firmicutes phyla, well Lactobacillus genera, aligning our model predictions. To enhance data accessibility facilitate targeted intervention development, launched an interactive webtool—mDiFiBank at https://mdifibank.org.cn/ .

Язык: Английский

---

Healthy gut microbiomes are host-controllable microbiomes

Frontiers in Microbiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

Introduction"The instinct of each species is good for itself but has never, as far we can judge, been produced the exclusive others" (1). Why, then, do humans and other mammals benefit from their microbes?Evolutionary theory predicts that natural selection act at organizational levels higher than gene or individual—such on groups even species—provided selective advantages group outweigh evolutionary conflicts. Darwin suggested "on family, not individual," "for sake gaining a serviceable end" This idea was later formalized kin (2). Even distantly related organisms align goals, demonstrated by longstanding partnership between eukaryotic cells mitochondria (3).Microbes are an integral part animal plant hosts, fulfilling essential physiological roles, such enabling access to otherwise unavailable nutrients, training immune system, supporting mucosal development, providing protection. Some microbes vertically transmitted parents offspring. The numerous examples performing vital functions macrobial hosts makes it tempting assume residing within our bodies—particularly in guts—evolved share common interests potential conflicts (4–7). Supporting this assumption, several reports suggest selected harboring "good" these thrive helping example, contributing over 95% organism's genetic repertoire (7–9). But group-level necessary sufficient mechanism explain why microbiomes hosts?Microbes certainly influence host's chances survival reproductive success (10,11) reasons would reduce own fitness form evolutionarily aligned with microbial populations—an condition selection—are easily explained (12,13). For during 25-year human generation, gut undergo more 50,000 generations (assuming conservative four-hour generation time), competing thousands species. Roughly half bacterial biomass colon lost daily replaced new growth (14,15). Before reproduces, any trait unfavorable microbe's likely be eliminated. Moreover, relatively open regularly exposed diverse environmental microbes. Vertical transmission accounts only small fraction microbiome. About twenty consistently shared among most adults (16). How, evolution shaped diverse, rapidly evolving ecosystem individual health?One might argue microbes, host mitigates conflicts, encouraging sacrifice some benefit. However, evolve, genotypes similar needs emerge exploit host-provided without incurring costs—an example tragedy commons (17). These benefits all compatible whether they contribute well-being, creating imbalance contributors free riders. A rider, could bacterium feeds mucin glycans provided while invading tissue potentially causing severe illness.Why, microbes? recent model Sharp & Foster suggests one way overcome conundrum evolve mechanisms actively control limit opportunities evade (18). require enforcement policing maintain cooperation (19). In view, "beneficial" ability healthy state. words, favor microbiome engineers—or, accurately, tinkerers (20)—who make use various methods reach landscape sustain include responses ranging rudimentary inflammation diarrhea sophisticated driven adaptive system. From perspective, theory—the study how systems regulate themselves achieve desired outcomes—parallels host-microbial interactions, suggesting be, definition, host-controllable microbiomes.Will large complex stable?In 1970s, writing Nature, Robert May proposed stability ecosystems complexity increases, particularly number strength interactions grow (21). analyzed simplified Generalized Lotka-Volterra (GLV) explore concept. simulates random communities where population sizes constrained resource availability (represented negative self-interactions) mutual positive influences another's growth. According GLV model, assembled predicted remain stable when sufficiently weak strong confined few (Figure 1). GLV-like models commonly applied microbiomes, stability/complexity trade-offs assumed hold (22,23). May's introducing controller—an agent directs system toward predetermined objective, through energy expenditure—is continuously stabilize unstable reshape stability-complexity Figure 1. Fraction controller 10,000 simulations. Random were simulated increasing interaction strengths numbers Each dot represents hundred simulations colored according resulted Dark blue dots indicate cases 100 unstable, dark red stable. white transition zone intermediate stability. results show adding controller—here idealized device senses microbiome's current composition adjusts rates guide composition—significantly increases range microbiomes. Stability, defined here following original refers returns equilibrium after perturbation based signs eigenvalues Jacobian matrix point. Increased diversity generally associated gut. patients suffering pathogen invasions, inflammation, colitis, inflammatory bowel disease, colorectal cancer reduced alpha compared controls. Similarly, factors aging, obesity, Western diet, urbanization also linked decline (24). Diversity necessarily cause microbiome, rather consequence indirect evidence control. effectively drives state, which, state occur absence (due, constraints). case, impaired, declines. biological systems, active instead diversity. laboratory techniques like media dilution-to-extinction procedures, which isolate single strains, antibiotics, physical barriers, extreme pH, heat conditions similarly nature, see reducing diversity, Hawaiian bobtail squid, isolates Vibrio fischeri ocean its light organ (25). less often appreciated promote greater control.An intriguing underexplored perspective controls declining may signal loss controllability, instance, established reactors simulate gastrointestinal tract significantly stool inocula (26). Although replicate physicochemical flow gut, lack host-control mechanisms, dynamically regulated factors. Overall, viewing interconnected, island-like ecosystem—where serves patch colonized dispersal, local diversification, selection, drift (27)—becomes clearer consider processes active, energy-expending efforts target composition, functions.Beyond extends "state-space," includes populations biochemical activities. ideal scenario tight, full-state control, both abundance function population, including chemical outputs inputs. realistic involves limited, partial-state exerts varying degrees distinct aspects state-space. theoretical framework controlled targeting specific sets referred "minimal elements" (28). achieved leveraging species-species chains connecting external controllers intrinsic dynamics community still lacks empirical validation, highlights identifying elements restore dysbiotic microbiome.How helps microbiomesThe mammalian contains (29,30), categorized into microbiome-independent microbiome-dependent processes. transit time ranges two five hours intestine ten fifty-nine (31). parameters directly microbiome—favoring absorption fermentation intestine—but independent sensing features. open-loop (32)—that is, operate feedback itself. By contrast, system's features exemplifies closed-loop controller, actions dynamics. Evolving allowed fine-tune maximize large, densely populated meta-study comparing cultures fresh samples that, degrees, environment (e.g., SHIME, TIM-2) found interindividual variation inoculum primary driver (33)—i.e., outweighs pressure exerted reactor's operational design (biotope). ensures widely different, personalized communities, lifetime, continue perform despite variability.Controllability observability fundamental controlIf then need experimental elucidate control: (which state-space observe?) controllability states inputs, ideally finite time?). Numerous studies associate high consumption simple sugars low dietary fiber intake underlying debated. One possible explanation observability.Experiments synthetic substrates result history dependence, diverge taxonomic (34–36). lead deterministic compositions, (37). Put simply, multiple grown substrates, isolated same source maintained under identical (35). subset correspond communities. states. tend converge compositions metabolic profiles, regardless sources (37,38). scenario, outside reach. richness respond poorly therapeutic interventions, restriction immunotherapy (39).Controllability inherently dependent observability. Specifically, colonization events educate recognize pathogens enhance monitor Bacteroides fragilis produces immunomodulatory polysaccharide germ-free mice, trains protect against Helicobacter hepaticus, responsible colitis immunocompromised animals (40,41). Another segmented filamentous bacteria (SFB) (Candidatus Arthromitus), species-specific guts vertebrates. SFB forms millimeter-long filaments attach ileal epithelium via specialized cell called holdfast, triggering (42). species, peaks early life (43), future invasive pathogens.Interestingly, occupies spatial gradient cable bacteria, oxygen-rich anoxic lumen. morphology—long, single-layered filaments—it remains tested plays ecological role conducting electrons zones (44) sharing them (45). Ericsson colleagues observed mice exoelectrogenic fuel cells, though electrodes (46). Their showed differences electrical production exoelectrogens predictive lymphocyte trafficking unique signatures locations unusual signatures. adapting response redox gradients, observe react changes state-space.Host-microbiome dynamics: Pinocchio GeppettoOverall, incurs costs host, gathering information acting information. minimize invest reproduction. Over different timescales, arms race develops populations: efficient, cost-effective strategies, ways control—especially restricts (29). systemic counter invasion. When triggered, reactive oxygen released. opportunistic tolerating released hydrogen peroxide expressing molecular machinery allows absorb cytoplasm. There, quickly convert respiratory chain, giving advantage fermentative (47). Salmonella enterica serotype Typhimurium goes step further. Under normal conditions, detoxifies sulfide, quantities microbiota, converting thiosulfate. During thiosulfate tetrathionate, S. respires (48), feeding defense mechanisms.A healthy, symbiotic regulatory ensure beneficial function. arises impaired—whether because becomes unreachable, cues become unobservable, (effectors) ineffective. Geppetto (49); instead, attempt them. Like Pinocchio, strive—and succeed—to

Язык: Английский

---

Symbionts of predatory protists are widespread in the oceans and related to animal pathogens

Cell Host & Microbe, Год журнала: 2025, Номер 33(2), С. 182 - 199.e7

Опубликована: Фев. 1, 2025

Язык: Английский

---

The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations

Brain Sciences, Год журнала: 2025, Номер 15(2), С. 195 - 195

Опубликована: Фев. 14, 2025

Most brain development occurs in the "first 1000 days", a critical period from conception to child's second birthday. Critical processes that occur during this time include synaptogenesis, myelination, neural pruning, and formation of functioning neuronal circuits. Perturbations first days likely contribute later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, maturation colonization infant microbiome its metabolites, specifically neurotransmitters, immune modulators, vitamins, short-chain fatty acids. Successful gut-brain axis function depend on maternal factors (stress exposure toxins pregnancy), mode delivery, quality postnatal environment, diet after weaning breast milk, nutritional deficiencies. While neonatal highly plastic, it remains prone dysbiosis which, once established, may persist into adulthood, thereby inducing chronic inflammation abnormal excitatory/inhibitory balance, resulting excitation. Both are recognized as key pathophysiological ALS.

Язык: Английский

---

Amphibian skin bacteria contain a wide repertoire of genes linked to their antifungal capacities

World Journal of Microbiology and Biotechnology, Год журнала: 2025, Номер 41(3)

Опубликована: Фев. 27, 2025

Язык: Английский

---

The oncobiome; what, so what, now what?

Microbiome Research Reports, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 27, 2025

Microbial communities inhabiting various body sites play critical roles in the initiation, progression, and treatment of cancer. The gut microbiota, a highly diverse microbial ecosystem, interacts with immune cells to modulate inflammation surveillance, influencing cancer risk therapeutic outcomes. Local tissue microbiota may impact transition from premalignant states malignancy. Characterization intratumoral increasingly reveals distinct microbiomes that influence tumor growth, responses, efficacy. Various bacteria species have been reported therapies through mechanisms such as altering drug metabolism shaping microenvironment (TME). For instance, or bacterial enzymatic activity can convert prodrugs into active forms, enhancing effects or, conversely, inactivating small-molecule chemotherapeutics. Specific also linked improved responses immunotherapy, underscoring microbiome’s role Furthermore, unique signatures patients, compared healthy individuals, demonstrate diagnostic potential microbiota. Beyond gut, tumor-associated local affect therapy by inflammation, resistance. This review explores multifaceted relationships between cancer, focusing on their modulating TME, activation, members represents promising avenue for advancing precision oncology improving patient By leveraging biomarkers interventions, new strategies be developed optimize diagnosis treatment.

Язык: Английский

---

Aromatics from fossil fuels and breast cancer

iScience, Год журнала: 2025, Номер unknown, С. 112204 - 112204

Опубликована: Март 1, 2025

Polycyclic aromatic hydrocarbons (PAHs) from fossil fuels initiate breast cancer in animal models, and humans a link between PAH exposure risk has been established. In women, it takes approximately two decades for PAH-exposed cells to progress diagnosable cancer, the needs happen during time window when is vulnerable PAHs. Further, not everyone exposed high levels of PAHs develops cancer. are most likely lead initiation among individuals who were utero through pregnant mothers environmental pollutants or maternal obesity both. These early life exposures shown increase daughter's later susceptibility by causing daughter (1) an number structures which place, (2) suppression, perhaps epigenetically, ability repair DNA damage caused inhibiting expression tumor suppressor genes, (3) persistent gut dysbiosis, then impacts immune microenvironment. Among that may be volatile BTEX compounds. Thus, aromatics involved efforts should directed toward reducing human these compounds prevent

Язык: Английский

---

Ferroptosis-Related Genes as Molecular Markers in Bovine Mammary Epithelial Cells Challenged with Staphylococcus aureus

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2506 - 2506

Опубликована: Март 11, 2025

Staphylococcus aureus-induced mastitis is a significant cause of economic losses in the dairy industry, yet its molecular mechanisms remain poorly defined. Although ferroptosis, regulated cell death process, associated with inflammatory diseases, role bovine unknown. In this study, 11 S. aureus strains were isolated from milk samples obtained cows clinical or subclinical mastitis. Transcriptome analysis Mac-T cells challenged identified differentially expressed genes (DEGs). Enrichment revealed associations between DEG clusters and traits related to KEGG pathway enrichment Toll-like receptor, TNF signaling as significantly enriched pathways. Weighted gene co-expression network (WGCNA) further prioritized ferroptosis-related (HMOX1, SLC11A2, STEAP3, SAT1, VDAC2) involved iron metabolism. Notably, expression levels HMOX1 SAT1 increased aureus-challenged cells, upregulation was consistent trends observed transcriptome data mother–daughter pairs caused by infection. Furthermore, Ferrostatin-1 treatment reduced confirming involvement ferroptosis process. This study reveals that plays key highlights potential target for breeding strategies aimed at improving resistance.

Язык: Английский

---