The authors ground their argument in an ecological reframing of why fungi make these toxins in the first place. Mycotoxins emerge from specialised biosynthetic machinery, including polyketide synthases, non-ribosomal peptide synthetases and terpenoid pathways, and recent surveys have reported more than 900 new fungal metabolites, predominantly polyketides, terpenoids and peptides. Rather than evolving to poison mammals, aflatoxin production increases the fitness of Aspergillus flavus by up to 26-fold against insect herbivores while suppressing competing soil microorganisms, a trade-off that persists in natural populations. The same biosynthetic continuum yields antibiotics, antifungals and immunosuppressants, suggesting that the line between mycotoxin and pharmaceutical reflects the producer organism and the exposure context rather than any fundamental chemical mechanism. When dietary mycotoxins reach the gut, they therefore encounter a microbial community that treats them much as it treats any xenobiotic, transforming them enzymatically, binding them physically and, in some cases, releasing them back into active forms.

Microbial metabolism governs mycotoxin fate through conserved mechanisms whose relative contributions depend on the chemistry of the toxin and the composition of the microbiome. Detoxification is exemplified by the de-epoxidation of deoxynivalenol, the most prevalent Fusarium trichothecene, into the far less toxic metabolite DOM-1. Bioactivation runs in the opposite direction: zearalenone can be converted by gut bacteria into alpha-zearalenol, a compound with greater estrogenic activity than its precursor. Microbial cell walls, particularly the peptidoglycan of Lactobacillus and Bifidobacterium strains, adsorb aflatoxin B1 and reduce its free absorption in the small intestine. Meanwhile, microbial deconjugation during enterohepatic cycling can prolong systemic exposure, and masked plant-derived mycotoxins, such as deoxynivalenol-glucosides, can be hydrolysed by colonic beta-glucosidases back into their toxic aglycones in species- and site-dependent ways. The authors emphasise that mycotoxin fate is therefore shaped by microbiota-specific metabolic capacity rather than being intrinsically fixed.

Aflatoxin B1, a Group 1 human carcinogen that contaminates maize, peanuts and animal feed in warm climates, illustrates how epithelial injury intersects with microbiome-dependent immune dysfunction. Multiple microbial taxa degrade aflatoxin B1 through reductive and oxidative ring-modifying pathways that diverge fundamentally from hepatic cytochrome P450 bioactivation, including laccase-mediated oxidation from Bacillus licheniformis and Streptomyces species, F420H2-dependent reductases from mycobacteria and peroxidase-mediated degradation from Pleurotus ostreatus. These activities avoid epoxidation into the DNA-reactive aflatoxin B1-8,9-epoxide, the metabolite responsible for hepatic carcinogenicity. Yet the microbiome also amplifies aflatoxin toxicity. In mice, antibiotic-mediated microbiota depletion eliminated aflatoxin-induced splenic pyroptosis, while faecal microbiota transplantation and even sterile faecal filtrate transfer recapitulated hepatic pyroptosis, implicating gut-derived pipecolic acid and norepinephrine as causal microbial mediators that activate TLR4 and NLRP3 inflammasome signalling, driving caspase-1 activation, gasdermin D cleavage and the release of interleukin-1beta and interleukin-18.

Ochratoxin A, classified as a Group 2B possible human carcinogen and found in cereals, dried fruits, coffee, wine and cocoa, poses sustained dietary risk owing to its chemical stability, long biological half-life and renal accumulation. Microbial detoxification proceeds primarily through carboxypeptidase- and peptidase-mediated hydrolysis into the less toxic ochratoxin alpha, together with cell-wall-mediated binding. Fermented food consortia, particularly Tibetan kefir communities enriched in Lactobacillus kefiranofaciens and Kazachstania species, bind and degrade ochratoxin A through multivalent interactions involving cell wall beta-glucans, polysaccharides and peptidoglycans. In vivo, kefir intervention lowered ochratoxin burden, restored tryptophan and NAD+ homeostasis, upregulated tight junction proteins including claudin-1, occludin and ZO-1, and reduced liver enzyme levels, with metabolomics confirming glycerophospholipid rebalancing. Without such protection, ochratoxin A downregulates tight junction proteins through reactive oxygen species, calcium and myosin light chain kinase-dependent signalling, induces mitochondrial ROS and caspase-dependent apoptosis, and depletes tryptophan-metabolising taxa, weakening aryl hydrocarbon receptor signalling and regulatory T cell function while LPS translocation activates hepatic TLR4 and exacerbates inflammation.

Fumonisin B1, prevalent in maize due to Fusarium contamination, competitively inhibits ceramide synthase, disrupting de novo sphingolipid biosynthesis and driving the characteristic elevation in sphinganine-to-sphingosine ratios used as a biomarker of exposure. Gut-associated lactobacilli contribute to detoxification through esterase- and amidase-mediated hydrolysis that removes tricarballylic acid side chains to form hydrolysed fumonisin B1. Among the best-characterised bacteria, Lactobacillus pontis, L. amylovorus and L. ultunensis isolated from porcine caecum converted fumonisin B1 via surface adsorption followed by enzymatic hydrolysis, achieving up to approximately 50 percent conversion within 48 hours in vitro. However, hydrolysed fumonisin B1 retains biological activity and can sustain intestinal and hepatic injury through MAPK- and NF-kappaB-dependent pathways largely independent of sphingolipid disruption. Comparative animal studies demonstrate that both compounds compromise epithelial barrier integrity, alter gut microbial composition, reduce short-chain fatty acid production by 40 to 60 percent and disrupt hepatic metabolism, although effects are generally milder following exposure to the hydrolysed form. Antibiotic treatment eliminated 75 to 80 percent of fumonisin hepatotoxicity, while faecal microbiota transplantation reproduced hepatic injury, confirming the microbiome as a causal determinant of systemic toxicity.

The trichothecenes deoxynivalenol and T-2 toxin exert toxicity primarily through inhibition of translation and activation of ribotoxic stress pathways that phosphorylate eIF2alpha and engage MAPK and NF-kappaB cascades. Deoxynivalenol reshapes intestinal microbial communities and compromises barrier function, and these effects were partially mitigated by selected strains of Bacillus velezensis, which restored tight junction protein expression, suppressed TLR4/NF-kappaB signalling and normalised microbial composition and short-chain fatty acid profiles. Lactobacillus rhamnosus GG binds deoxynivalenol via S-layer proteins and rescues food intake in anorexia models, increasing butyrate and lowering TNF-alpha and interleukin-6. For T-2 toxin, microbiota-dependent activation of interleukin-6/Janus kinase/signal transducer and activator of transcription 1 signalling mediates splenic injury, as the phenotype was abolished by antibiotic treatment and recapitulated by faecal microbiota transplantation. Elemental nano-selenium attenuated this inflammatory response by reducing reactive oxygen species, suggesting that targeting microbiome-immune interactions may represent a viable strategy to reduce trichothecene toxicity. In contrast to aflatoxin and ochratoxin, evidence for binding-mediated sequestration of trichothecenes remains limited, indicating that biotransformation rather than adsorption is the dominant microbial mechanism influencing their toxicity.

Perhaps the most provocative implication concerns antimicrobial resistance. The authors highlight emerging evidence that deoxynivalenol exposure selectively enriches Gram-positive taxa carrying antibiotic resistance genes, particularly those associated with last-resort antibiotics such as daptomycin. Enterococcus faecalis isolated from deoxynivalenol-exposed microbiota showed extensive drug resistance, with resistance exceeding 128 micrograms per millilitre to daptomycin, vancomycin and linezolid. Deoxynivalenol-induced stress promotes genomic plasticity, enhances the co-occurrence and dissemination of resistance genes via mobile genetic elements, and increases reactive oxygen species production and membrane permeability, amplifying resistance phenotypes. Bacterial defence responses to the toxin converge with classical antibiotic resistance mechanisms, including activation of ATP-binding cassette transporters, toxin-detoxifying enzymes and stress-response proteins such as porins, glutathione S-transferases and phosphotransferases. The authors caution that deoxynivalenol is not an antimicrobial in the conventional sense but may act as a selective ecological pressure that favours resistant populations, and they note that evidence that aflatoxin, ochratoxin or zearalenone directly promote horizontal resistance gene transfer remains limited.

The authors are equally candid about the limitations of the evidence base. Most reports of mycotoxin-induced microbiota perturbation remain descriptive, with limited causal or functional resolution, and many experiments use high doses and non-human models whose relevance to real-world conditions, where exposure is usually chronic and low-dose, is uncertain. Reported microbiota responses are inconsistent, with deoxynivalenol, zearalenone and aflatoxin producing opposing shifts in Proteobacteria, Firmicutes and Bacteroidetes across experimental systems, likely reflecting differences in host biology, exposure intensity, duration and matrix composition. Results for Lactobacillus are particularly inconsistent despite its relevance in detoxification, and aflatoxin exposure can even increase Lactobacillus populations, raising mechanistic questions about whether microbial enrichment reflects adaptive detoxification, ecological resilience or selection for intrinsically resistant taxa with altered functional potential. High in vitro degradation or binding rates by probiotics do not necessarily persist in vivo because of gastric pH, transit time, competing food matrices, host metabolism and enterohepatic recirculation.

Looking ahead, Garcia-Cela and Marcon Gasperini call for a shift beyond descriptive microbiota profiling toward integrative frameworks that link microbial ecology, host physiology and metabolomic outputs. Priority areas include in vivo validation of microbial detoxification pathways, systematic comparison of in vitro and dietary exposure models, and strain-level functional characterisation to resolve inter- and intra-species variability in detoxification capacity. Multi-strain consortia, including kefir-like communities, are particularly attractive because they can couple adsorption, biodegradation and ecological competition within a single system. Engineered microbial systems could be designed to express defined detoxification enzymes or high-affinity binding modules, but their deployment will require careful evaluation of containment, regulatory approval and ecological impact. Future studies must also incorporate co-exposure scenarios, enterohepatic cycling and host-specific variables to enhance translational relevance, and mechanistic resolution of feedback loops between epithelial injury and microbial metabolic reprogramming will be essential to understand whether host-microbiome interactions amplify or constrain toxicity over time. The next generation of interventions, the authors suggest, will likely be modular, mechanism-based and tailored to the toxin, matrix and host context rather than dependent on any single probiotic solution.

Subject of Research: Microbiology / Toxicology

Article Title: Mechanistic evidence and assumptions in mycotoxin-gut interaction

Article References: Garcia-Cela, E., & Marcon Gasperini, A. (2026). Mechanistic evidence and assumptions in mycotoxin-gut interaction. Frontiers in Fungal Biology, 7, Article 1855881. https://doi.org/10.3389/ffunb.2026.1855881

Image Credits: AI Generated

DOI: 10.3389/ffunb.2026.1855881

Keywords: mycotoxins, gut microbiota, aflatoxin B1, ochratoxin A, fumonisin B1, deoxynivalenol, T-2 toxin, antimicrobial resistance, intestinal barrier, microbial detoxification, Mechanistic, evidence

Ochratoxin A (OTA) is one of the most concerning mycotoxins in the food supply. Classified by the International Agency for Research on Cancer as a group 2B agent—a possible human carcinogen—it carries nephrotoxic, immunotoxic, and teratogenic properties. While OTA contamination is well documented in cheese, no legal limits for the toxin in cheese currently exist, highlighting an urgent need for effective mitigation strategies. The European Food Safety Authority has identified cheese among the food categories contributing to chronic dietary OTA exposure in some consumer groups, making the search for solutions increasingly pressing.

Enter Debaryomyces hansenii. This yeast is one of the dominant species naturally found on the surfaces of many ripened cheeses, where it contributes positively to flavour development, proteolytic and lipolytic activities, and surface deacidification. It has been included in the European Qualified Presumption of Safety (QPS) framework since 2007, meaning regulators consider it safe for use in food. Previous research has shown that D. hansenii can limit ochratoxigenic fungi in fermented meats, but until now, no study had tested its effectiveness against A. westerdijkiae specifically on a cheese-like matrix.

The research team, led by scientists at the Institute of Sciences of Food Production (CNR-ISPA) in Bari, Italy, tested thirteen strains of A. westerdijkiae—twelve isolated from the surfaces of Italian cave cheeses and one from sorghum—against a single strain of D. hansenii (ITEM 19968), itself originally isolated from cheese. They used a Caciocavallo-based cheese agar medium designed to mimic the actual cheese environment from which the fungal strains were recovered.

The experimental design was straightforward but rigorous. The researchers inoculated the cheese agar with a suspension of D. hansenii at a concentration of 10⁶ cells per millilitre, then spotted fungal spores onto the surface in a symmetrical triangular pattern. Control plates received the fungal spores but no yeast. Plates were incubated for 20 days at 25°C in the dark, and mycelial growth was measured at 5, 10, 15, and 20 days post-inoculation. After the incubation period, the entire plate contents were collected and analysed for OTA using high-performance liquid chromatography with fluorometric detection.

The results revealed a striking temporal pattern. In the first five days, the interaction between the two microorganisms was heterogeneous: five of the thirteen fungal strains actually showed apparent growth stimulation in the presence of the yeast, with inhibition values ranging from −17% to +35%. However, by day 10, all thirteen strains exhibited reduced mycelial growth, with inhibition values ranging from 17% to 31%. These inhibition levels remained relatively stable through days 15 and 20, suggesting a sustained antagonistic effect once the yeast became established.

The most dramatic findings, however, concerned ochratoxin A production. At 20 days post-inoculation, OTA production was reduced by 63% to 100% across all toxin-producing strains. Seven strains—ITEM 9607, ITEM 18032, ITEM 19082, ITEM 19084, ITEM 19092, ITEM 19094, and ITEM 19095—showed complete inhibition, with OTA levels falling below the detection limit of 3 μg/kg. The control group’s baseline OTA production ranged from 5 to 1,603 μg/kg, meaning the yeast suppressed toxin output regardless of how intrinsically toxigenic each fungal strain was.

What makes these results particularly intriguing is that the reduction in OTA was proportionally greater than the reduction in fungal growth. This suggests that D. hansenii does not merely limit fungal proliferation but also directly interferes with the metabolic pathways involved in mycotoxin biosynthesis. Previous work by Gil-Serna and colleagues demonstrated that the yeast may downregulate genes involved in OTA production and adsorb the toxin onto its cell walls. The authors of the current study propose that nutrient competition, accumulation of yeast-derived metabolites, and modifications to the cheese environment’s physicochemical properties—such as lactate utilisation and surface pH increase—may all contribute to the observed antagonistic effects.

The temporal dynamics of the interaction are also noteworthy. The apparent stimulation of some fungal strains during the first five days likely reflects the yeast’s establishment phase, during which it adapts to the substrate and progressively alters local conditions without yet generating conditions restrictive enough to inhibit fungal growth. Once established, however, D. hansenii appears to create an environment hostile to both fungal expansion and toxin synthesis. This suggests that for practical applications in cheese ripening, the yeast would need to be active for at least ten days to exert meaningful biocontrol.

The researchers caution that their work was conducted under controlled laboratory conditions using a cheese-like medium, which may not fully replicate the complexity of real cheese ecosystems. The specific physiological and molecular mechanisms underlying the observed effects were not investigated and warrant further study using transcriptomic, metabolomic, and targeted biochemical approaches. Additionally, the sensory impact of the specific D. hansenii strain on cheese quality remains untested and must be evaluated under actual manufacturing conditions before practical application.

Nevertheless, the findings represent a significant step forward in the search for natural, sustainable solutions to mycotoxin contamination in dairy products. As consumer demand for clean-label foods grows and regulatory pressure on chemical preservatives intensifies, biocontrol approaches using microorganisms with a history of safe use in food fermentation are gaining traction. Debaryomyces hansenii, already a familiar inhabitant of cheese surfaces and a recognised contributor to cheese ripening, may soon play an even more important role—not just in shaping flavour and texture, but in actively protecting consumers from one of the food supply’s most persistent toxic threats.

Subject of Research: Biocontrol of ochratoxigenic Aspergillus westerdijkiae by Debaryomyces hansenii on cheese-like medium

Article Title: Debaryomyces hansenii as potential biocontrol agent against Aspergillus westerdijkiae and its ochratoxin A production on cheese-like medium

Article References: Carella, D., Cervellieri, S., Anelli, P., Gatto, A., De Girolamo, A., Lippolis, V., Moretti, A., & Susca, A. (2026). Debaryomyces hansenii as potential biocontrol agent against Aspergillus westerdijkiae and its ochratoxin A production on cheese-like medium. Current Research in Food Science, Article 101599. https://doi.org/10.1016/j.crfs.2026.101599

Image Credits: AI Generated

DOI: 10.1016/j.crfs.2026.101599

Keywords: Debaryomyces hansenii, Aspergillus westerdijkiae, ochratoxin A, mycotoxins, cheese ripening, biocontrol, food safety, yeast, dairy, biopreservation, Debaryomyces, hansenii

The scale of exposure is far from trivial. According to the Food and Agriculture Organization of the United Nations, roughly 25 percent of global crops are contaminated with mycotoxins, although the review notes that the true figure for detectable levels may exceed 60 percent. These fungal metabolites can invade food and feed at every stage of the food chain, from field to storage, and climate change together with poor storage conditions, including elevated water activity, temperature, and relative humidity, is expected to worsen fungal colonization and toxin production. Humans encounter mycotoxins through the respiratory system, the skin, and the gastrointestinal tract, with the diet representing the primary route of long-term exposure. Cereals such as maize are frequent carriers, while nuts are especially vulnerable to aflatoxins.

What makes the new synthesis particularly compelling is the accumulating evidence that several of these toxins can cross the blood-brain barrier, the highly selective endothelial fence that normally shields the brain from circulating hazards. Once inside, they accumulate in neural tissue and attack both neurons and glial cells. The review identifies a shared arsenal of damaging mechanisms: disruption of neuronal signalling pathways, DNA damage, epigenetic modifications, impaired neurogenesis, oxidative stress, dysregulated autophagy, interference with neurotransmitter systems, mitochondrial dysfunction, and neuroinflammation. The severity of the resulting neurological outcomes depends on the dose, duration, and timing of exposure, and has been linked to cognitive impairments, learning difficulties, behavioural abnormalities, and neurodegenerative and neurodevelopmental disorders, including Alzheimer’s and Parkinson’s diseases.

Ochratoxin A emerges as one of the most thoroughly characterized brain-seeking toxins. In rat brain cell cultures, OTA disrupts the neuronal cytoskeleton, reducing heavy neurofilament expression and altering oligodendrocyte maturation by decreasing myelin basic protein and myelin oligodendrocyte glycoprotein, structural changes that threaten neuronal function and myelination. Work on the mouse subventricular zone, a key neurogenic niche, showed that OTA impairs cell viability, proliferation, and differentiation in a dose-dependent manner, while chronic exposure damaged hippocampal cells in adult mice, a finding that may underpin learning and memory deficits. In three-dimensional brain cultures, OTA disrupted the cytoskeletons of neurons and astrocytes and triggered neuroinflammation. In human astrocytes, the toxin reduces proliferation, induces cell cycle arrest, and drives apoptosis through loss of mitochondrial membrane potential, while activating the JNK1/2 and p38 stress kinases, likely via disrupted calcium signalling. In microglia, OTA provokes release of the proinflammatory cytokines IL-1β, IL-18, and CXCL8, and in zebrafish it causes locomotor impairment alongside altered oxidative stress markers such as glutathione peroxidase and glutathione-S-transferase.

Zearalenone, an oestrogenic Fusarium toxin, attacks neurons through a different route. In human neuroblastoma SH-SY5Y cells it generates reactive oxygen species, lipid peroxidation, loss of mitochondrial membrane potential, and DNA double-strand breaks, with the metabolites α-zearalenol and β-zearalenol similarly disrupting the cell cycle. ZEN also activates the mitogen-activated protein kinase signalling cascade, a conserved pathway governing proliferation, survival, and apoptosis, with ROS acting as signalling intermediates that can tip cells toward programmed death. In the nematode Caenorhabditis elegans, long-term exposure induced mitochondrial fragmentation, upregulated fission and apoptosis genes, and suppressed the DAF-16/FOXO transcription factor, a central regulator of ageing and longevity, producing an ageing-related decline. In zebrafish larvae, ZEN inhibited muscle and neural development through caspase-8-dependent apoptosis and altered expression of neuronal markers including tyrosine hydroxylase and brain-derived neurotrophic factor, confirming its capacity to derail normal neuronal function.

Fumonisin B1 takes aim at cellular metabolism itself. In rat primary astrocytes and SH-SY5Y cells, FB1 inhibits mitochondrial complex I, depressing cellular respiration, depolarizing the mitochondrial membrane, spurring ROS production, and deregulating calcium signalling. Its signature lesion, however, lies in sphingolipid metabolism: by inhibiting ceramide synthases, FB1 blocks ceramide formation, causing sphinganine and sphingosine to accumulate while complex sphingolipids dwindle, a disruption tied to apoptosis, cell cycle derangement, and membrane dysfunction. This mechanism links fumonisins to equine leukoencephalomalacia and, in humans, to neural tube defects. FB1 also renders neurons more vulnerable to glutamate-induced excitotoxicity, alters GABAergic and serotonergic systems in C. elegans with resulting behavioural deficits, and suppresses immune function by impairing dendritic cell maturation and cytokine secretion, compounding the neurological threat with immunological vulnerability.

Aflatoxin B1, described in the review as the most potent natural carcinogen known, is equally formidable in the brain. In primary microglial cells it triggers lactate dehydrogenase leakage, DNA damage markers, nuclear lysis, and release of IL-1β, IL-18, and TNF-α, activating the NLRP3 inflammasome and gasdermin D-mediated pyroptosis, an inflammatory form of cell death that fuels neuroinflammation and neuronal loss. In astrocytes it causes cell cycle arrest and mitochondrial apoptosis involving Bax, Bak, and cytochrome C, while in zebrafish embryos it inhibits Na+/K+-ATPase in brain synaptosomes, producing hyperlocomotion and suppressing neurogenesis genes. Repeated administration in rats degenerates central and peripheral nerve fibres and myelin sheaths, alters biogenic amines governing cognition and memory, and disrupts hypothalamic neuropeptide balance. The toxin’s liver-derived reactive epoxide metabolite, AFB1-8,9-epoxide, is central to this oxidative assault on neural tissue.

The trichothecene T-2 toxin and deoxynivalenol round out the roster. T-2, considered the most toxic trichothecene, dismantles the cellular redox balance, overwhelming antioxidant defences and damaging lipids, proteins, and DNA; it impairs mitochondria in mouse primary neurons and N2a cells, activates caspases 8, 9, and 3 through both intrinsic and extrinsic apoptotic routes, and suppresses the Nrf2/HO-1 antioxidant defence axis. Critically, T-2 also breaches the blood-brain barrier itself, via oxidative stress and activation of matrix metalloproteinase-9, which degrades the extracellular matrix proteins collagen, laminin, and fibronectin that hold endothelial tight junctions together, inviting immune cells into the brain. DON, meanwhile, drives mitochondrial apoptosis in PC12 and hippocampal cells through Bcl-2 family mediators and p53, induces G1 cell cycle arrest in glial and hippocampal cells, shrinks dendritic arborization, shifts neurotransmitter levels, with norepinephrine and serotonin rising as dopamine and GABA fall, and triggers autophagy through the PI3K/Akt/mTOR pathway.

The review’s authors stress that, compared with other organ systems, research on mycotoxin effects on the brain remains limited, and they call for intensified study of the toxin-neuron interface to identify new drug targets within the central nervous system. They argue that protecting the public demands a comprehensive strategy spanning regulatory measures, improved agricultural and manufacturing practices, public awareness, and sustained research collaboration, alongside urgent risk assessment and stricter legislation covering both established and emerging mycotoxins in daily diets. As contamination pressures grow with a changing climate, the message of this synthesis is stark: the fungi that colonize the world’s staple crops may be quietly shaping brain health on a global scale, and the scientific community is only beginning to map the full extent of the damage.

Subject of Research: Neurotoxicity mechanisms of food-borne mycotoxins

Article Title: A scoping review on mycotoxin-induced neurotoxicity

Article References: Abia, W. A., Foupouapouognigni, Y., Nfombouot, H. P. N., Ngoungoure, L. V. N., Ntungwe, E. N., Salah-Abbès, J. B., & Tchana, A. N. (2025). A scoping review on mycotoxin-induced neurotoxicity. Discover Toxicology, 2(1), Article 1. https://doi.org/10.1007/s44339-024-00013-7

Image Credits: AI Generated

DOI: 10.1007/s44339-024-00013-7

Keywords: mycotoxins, neurotoxicity, blood-brain barrier, aflatoxin B1, ochratoxin A, fumonisin B1, zearalenone, T-2 toxin, deoxynivalenol, oxidative stress, neuroinflammation, food safety

Mycotoxins are toxic secondary metabolites produced by fungi, and more than 400 different types have been identified from over 100 fungal strains. They contaminate agricultural products through molds such as Aspergillus, Penicillium, and Fusarium, and by some estimates roughly a quarter of the world’s crops, including cereals, pulses, oilseeds, and nuts, are affected by mold and fungal contamination. Humans and animals are exposed mainly through ingestion, though dermal and inhalation routes also matter, and the severity of harm depends on the toxin type, the dose and duration of exposure, nutritional status, and interactions with other chemicals. Because real-world diets rarely contain a single contaminant, the question of how mycotoxins interact inside the body is not academic; it is central to food safety.

Aflatoxin is among the most notorious of these compounds. Produced primarily by Aspergillus flavus, A. parasiticus, A. nomius, and A. aflatoxiformans, the aflatoxin family includes 18 known types, of which AFB1, AFB2, AFG1, AFG2, AFM1, and AFM2 are the most toxic and are classified as Group 1 carcinogens. The liver is the primary target. Aflatoxin B1 is metabolized by microsomal CYP450 enzymes into AFB1-8,9-epoxide, a highly reactive form that binds DNA and proteins and drives tissue toxicity; a characteristic G to T transversion at codon 249 of the P53 gene has been linked to aflatoxin-induced hepatocellular carcinoma. An estimated 28 percent of hepatocellular carcinoma cases worldwide are associated with AFB1 exposure, and acute aflatoxicosis outbreaks have been reported in India, Kenya, and Tanzania.

Ochratoxin A, the second toxin in the study, is produced by filamentous fungi including Aspergillus and Penicillium species and exists in three forms, with OTA being the most toxic and the most frequently detected in food and feed. It exerts a remarkably broad toxicological portfolio: mutagenicity, hepatotoxicity, neurotoxicity, nephrotoxicity, teratogenicity, and immunotoxicity. OTA has been implicated as a possible etiological factor in Balkan Endemic Nephropathy, a mysterious tubulo-interstitial kidney disease seen in the Balkan Peninsula and Romania, and has been associated with chronic interstitial nephropathy in humans as well as renal and urothelial cancers in rats. Unlike aflatoxin, OTA is considered a cumulative toxin, building up in the body through repeated dietary exposure.

To test what happens when these two contaminants meet, the team, led by Kanchan Gopal Choudhary of Patna University together with colleagues at Mahavir Cancer Sansthan and Research Centre, ran a carefully controlled sub-acute toxicity experiment. Adult male Charles Foster rats, roughly eight weeks old and weighing 160 to 180 grams, were randomly assigned to groups receiving aflatoxin at 0.9 milligrams per kilogram of body weight per day, ochratoxin A at 2.75 milligrams per kilogram per day, or a combined half-dose regimen of 0.45 plus 1.375 milligrams per kilogram per day, with untreated controls for comparison. Each treatment arm was subdivided into 30-, 45-, and 60-day exposure periods. The toxins themselves were extracted from toxigenic fungal cultures, aflatoxin from Aspergillus flavus isolated from contaminated stored wheat and ochratoxin A from Aspergillus niger isolated from contaminated sesame seeds, and their concentrations were verified by thin-layer chromatography and high-performance liquid chromatography with fluorescence detection.

The hematological findings pointed to anemia across the single-toxin groups. Aflatoxin-treated rats showed significant drops in red blood cell counts, hemoglobin, platelets, lymphocyte percentage, basophil counts, and packed cell volume, alongside rises in neutrophil percentage, mean corpuscular volume, and mean corpuscular hemoglobin, a pattern consistent with normocytic normochromic anemia. The ochratoxin A group displayed a similar but distinct signature, with reduced red cells, platelets, packed cell volume, lymphocytes, monocytes, and basophils and elevated MCV, MCH, and MCHC, suggesting normocytic hypochromic anemia. The authors attribute these declines to mechanisms including hematopoietic cellular abnormalities, reduced iron-binding capacity, and inhibition of protein synthesis through decreased serum albumin. Notably, the combined-exposure group produced no clear hematological pattern at all, an early hint that co-exposure behaves in unpredictable ways.

Liver chemistry told a story of accumulating hepatic stress. Serum AST, a transaminase released when hepatocytes die, rose significantly in the 60-day groups of all three treatment arms, while alkaline phosphatase climbed significantly in the aflatoxin and ochratoxin A groups. Other liver markers, including ALT, total bilirubin, and direct bilirubin, remained unchanged, indicating that prolonged rather than short-term exposure is what tips the liver into measurable dysfunction. Under the microscope, the damage tracked the biochemistry: aflatoxin-treated livers progressed from cytoplasmic vacuolization and sinusoidal dilation at 30 days to focal necrosis at 45 days and, by 60 days, degenerated cytoplasm, irregular Kupffer cell nuclei, and mild hepatic steatosis. Ochratoxin A and the combination produced comparable trajectories of ballooning hepatocytes, periportal hemorrhage, mononuclear infiltration, and necrosis, with quantitative scoring of degeneration among 100 hepatic cells per animal confirming steadily worsening injury over time.

The kidney results were where the study took its most unsettling turn. In aflatoxin-treated rats, creatinine, a standard marker of renal filtration failure, rose significantly at 30 and 45 days but returned to near-control values by 60 days, a rebound the authors suggest may reflect induction of cytochrome P-450 enzymes such as CYP3A4 that metabolize aflatoxin with prolonged exposure. Ochratoxin A produced the expected nephrotoxic profile, with uric acid elevated at 45 days and creatinine elevated at both 45 and 60 days, confirming dose- and time-dependent renal injury. Histologically, all treated groups showed glomerular degeneration, damage to the brush border of Bowman’s capsule, cytoplasmic vacuolization of the epithelial lining, and degeneration of proximal and distal convoluted tubules, with hemorrhages inside Bowman’s capsule appearing in the combined group by 60 days.

The combination group, however, broke the expected correlation between blood chemistry and tissue damage. Creatinine rose significantly only at 45 days and had normalized by 60 days, while uric acid, urea, and blood urea nitrogen never significantly changed, yet histopathological analysis of the same animals revealed chronic, progressive kidney toxicity, including tubular destruction, glomerular degeneration, and hemorrhage. In other words, the laboratory values suggested recovery or tolerance at precisely the time point when the tissue showed the most severe structural damage. The authors conclude that aflatoxin plus ochratoxin A may act as a silent toxicant, one that evades the standard biomarker panel used to detect kidney injury, and they caution that biochemical normality should not be mistaken for histological health in co-exposure scenarios.

The findings carry real-world weight because co-contamination of food and feed with multiple mycotoxins is the norm rather than the exception, and regulatory limits are typically set toxin by toxin. If half-doses of two common contaminants can quietly destroy renal tissue while leaving blood tests clean, current monitoring strategies may systematically underestimate the health burden of mycotoxin mixtures, particularly in regions where dietary exposure is chronic and healthcare diagnostics rely heavily on serum chemistry. The authors acknowledge a key limitation: toxin levels in the blood were not measured, so pharmacokinetic interactions between aflatoxin and ochratoxin A remain to be characterized. Follow-up studies tracking co-exposure with direct toxin quantification, and ideally with more sensitive kidney injury biomarkers beyond creatinine, will be needed to confirm how generalizable this silent-toxicity phenomenon is, and whether human populations eating contaminated staples face the same invisible risk.

Subject of Research: Sub-acute toxicity of combined aflatoxin and ochratoxin A exposure in Charles Foster rats

Article Title: Synergistic impact of aflatoxin and ochratoxin A exposure in Charles foster rats: a toxicological study

Article References: Choudhary, K. G., Sharfuddin, C., Kumar, A., & Ghosh, A. K. (2025). Synergistic impact of aflatoxin and ochratoxin A exposure in Charles foster rats: a toxicological study. Discover Toxicology, 2(1), Article 16. https://doi.org/10.1007/s44339-025-00036-8

Image Credits: AI Generated

DOI: 10.1007/s44339-025-00036-8

Keywords: aflatoxin, ochratoxin A, mycotoxins, nephrotoxicity, hepatotoxicity, silent toxicity, Charles Foster rats, food safety, normocytic anemia, histopathology, creatinine, toxicology

The research team, led by Imane E.L. Houssni, screened 1,055 records retrieved from Scopus, Web of Science, PubMed and ScienceDirect and retained 388 high-rigor studies after a PRISMA-guided triage that eliminated uncharacterized adsorbents, superficially descriptive biocontrol assays and reports lacking mass-balance verification. Inter-reviewer agreement was high, with a Cohen’s kappa of 0.88. The resulting synthesis organizes the field around a four-pillar framework: upstream inhibition of toxigenic fungi, passive physical sequestration, active enzymatic biotransformation, and downstream protection of the host’s intestinal barrier.

The first mechanistic pillar, biosorption, is deceptively simple. Toxin molecules bind to the microbial cell wall, a scaffold of peptidoglycan, teichoic acids, beta-glucans and surface-layer proteins, through electrostatic attraction, hydrophobic intercalation and steric entrapment. Crucially, this process does not require living cells. Heat-killed paraprobiotics work just as well, sidestepping risks of horizontal gene transfer in processed foods. Spectroscopic and microscopy studies show that peptidoglycan cross-linking and the charge density of teichoic acids dictate binding stoichiometry, while yeast beta-glucan triple helices form high-affinity pockets that capture zearalenone through hydrophobic insertion of its macrocyclic lactone ring.

Yet the review is blunt about biosorption’s Achilles heel: reversibility. Binding equilibria that look impressive in a static flask can collapse in the gut, where pH swings from gastric acidity to intestinal neutrality, bile salts micellize lipophilic toxins, digestive enzymes chew up cell-wall proteins, and peristaltic shear pries complexes apart. The authors argue that static isotherm parameters such as maximum adsorption capacity cannot be extrapolated to prove in vivo sequestration; definitive validation demands dynamic multi-compartmental simulators like TIM-1 and SHIME, plus fecal recovery assays.

The second pillar, enzymatic biotransformation, offers a permanent solution by chemically remodeling toxic pharmacophores. Lactonohydrolases of the ZHD102 family cleave zearalenone’s macrocyclic ester into hydrolyzed ZEN, a product devoid of estrogenic activity. Anaerobic gut commensals such as Eubacterium BBSH 797 express epoxide reductases that convert deoxynivalenol into the non-toxic DOM-1, disarming the molecule’s ability to inhibit ribosomal protein synthesis. For ochratoxin A, metalloproteases cleave the amide bond linking the phenylalanine moiety to the isocoumarin nucleus, yielding ochratoxin alpha, which is negligibly toxic and rapidly cleared by the kidneys. Fumonisin B1 detoxification proceeds in two steps: a carboxylesterase such as FumD strips the tricarballylic acid side chains, then an aminotransferase deaminates the C-2 amine, abolishing the toxin’s interference with ceramide synthase.

But the review insists on a critical caveat: biotransformation is not automatically detoxification. Some conversions backfire spectacularly. Zearalenone can be reduced to alpha-zearalenol, which binds estrogen receptors more avidly than the parent toxin. Genuine detoxification therefore requires full structural identification of every degradation product by high-resolution mass spectrometry or NMR, complete mass-balance closure, and bioassay-driven toxicological validation to rule out masked or paradoxically toxic intermediates.

The third and most surprising pillar reframes probiotics as biological shields rather than mere toxin sponges. Administered strains fortify the intestinal epithelium by upregulating tight junction proteins, including zonula occludens-1, occludin and the claudins, while suppressing the pathological hyperactivation of p38 MAPK and NF-kappa-B that deoxynivalenol and ochratoxin A trigger through ribotoxic stress. They also stimulate goblet cells to thicken the MUC2 mucus layer, promote secretory IgA secretion from gut-associated lymphoid tissue, and activate the host’s Nrf2 antioxidant pathway to restore the glutathione redox ratio. Perhaps most strikingly, postbiotic metabolites such as butyrate act as histone deacetylase inhibitors, a postbiotic-epigenetic bridge that remodels chromatin and transcriptionally reprograms barrier-restoring genes.

In the food industry, these mechanisms are converging on the concept of smart starters, bifunctional cultures that ferment the product while scrubbing it clean. Multi-strain lactobacilli consortia have achieved aflatoxin M1 reductions exceeding 60 percent in yogurt models, Lactiplantibacillus plantarum strains bind 65 to 85 percent of aflatoxin B1 in sourdough matrices, and the yeast Kluyveromyces marxianus removes 85 to 95 percent of zearalenone while enriching products with aromatic esters and B vitamins. The challenge is preserving taste and texture: over-acidification, off-flavors and proteolytic degradation can sink consumer acceptance regardless of molecular efficacy, and matrix components like milk fat can physically shield toxins from microbial contact.

The review also confronts the field’s methodological blind spots. Two strains of the same species can differ in binding capacity from under 10 percent to over 80 percent, real-world contamination involves multi-toxin cocktails that saturate binding sites, and masked mycotoxins such as deoxynivalenol-3-glucoside evade screening until gut hydrolases release the parent toxin in situ. Human trials remain scarce and often rely on indirect urinary biomarkers, while responder-versus-non-responder microbiome heterogeneity complicates regulatory validation by EFSA and the FDA.

Looking forward, the authors sketch a roadmap toward designer microbes: CRISPR-engineered chassis with densified adsorptive cell walls and heterologous detoxification enzymes, programmable biosensors that secrete enzymes only when luminal toxin spikes are detected, artificial intelligence-driven molecular docking to predict binding energies, gut-on-a-chip platforms and human intestinal organoids for physiologically faithful validation, and pH-responsive nano-encapsulation that delivers payloads exactly where absorption risk peaks. The smart starter concept currently sits at low technology readiness levels, but the trajectory is clear. Fermented foods, once viewed as a passive vector of dietary risk, are being reimagined as precision instruments of xenobiotic resilience, turning the trillions of microbes in our food and gut into an active, engineered line of defense against one of the oldest poisons in the human diet.

Subject of Research: Microbial mechanisms of mycotoxin detoxification in fermented foods and the gastrointestinal tract

Article Title: Microbial mycotoxin mitigation across the microbe–matrix–host continuum: mechanisms, fermented-food applications, and gastrointestinal translation

Article References: HOUSSNI, I. E., ZAHIDI, A., FAKIR, S. E., JAIMA, W., & HASSIKOU, R. (2026). Microbial mycotoxin mitigation across the microbe–matrix–host continuum: mechanisms, fermented-food applications, and gastrointestinal translation. Current Research in Biotechnology, Article 100421. https://doi.org/10.1016/j.crbiot.2026.100421

Image Credits: AI Generated

DOI: 10.1016/j.crbiot.2026.100421

Keywords: mycotoxins, probiotics, biosorption, biotransformation, lactic acid bacteria, fermented foods, gut barrier, aflatoxin, zearalenone, ochratoxin A, smart starters, food safety

The research drew on residual blood samples collected during the 2019 endline survey of the FAARM trial, a cluster-randomized study conducted in rural Bangladesh. In total, 719 participants—433 women and 286 children—were included in the investigation. The team, led by Nicholas N. A. Kyei of the Institute of Public Health at Charité – Universitätsmedizin Berlin together with colleagues at Heidelberg University, the Potsdam Institute for Climate Impact Research, and the Institute of Food Chemistry at Universität Münster, analyzed 712 whole blood and 578 serum samples using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry, or UHPLC-MS/MS. This technique can detect and quantify multiple fungal toxins and their metabolites at vanishingly low concentrations, making it the gold standard for human biomonitoring of mycotoxins.

The starkest result concerned ochratoxin A, a nephrotoxic and possibly carcinogenic mycotoxin produced by Aspergillus and Penicillium fungi that frequently contaminates cereals, spices, and dried fruit. OTA was detected in 100 percent of whole blood samples, and its lesser-known isomer, 2′R-ochratoxin A, appeared in 98 percent. Citrinin, a toxin produced by the same fungi and known to damage the kidneys, was found in 91 percent of samples, while Enniatin B, an emerging mycotoxin with antimicrobial and cytotoxic properties, was present in 92 percent. Beauvericin, another emerging toxin, was detected in 6 percent of samples. The sheer ubiquity of these compounds in human blood underscores how difficult it is to avoid mycotoxin exposure where contaminated staple foods form the daily diet.

Perhaps the most consequential finding involved aflatoxin B1, one of the most potent liver carcinogens known to science. Because AFB1 itself is rapidly metabolized, researchers instead measured AFB1-lysine adducts—molecules formed when the toxin’s reactive metabolite binds covalently to the blood protein albumin. Serum samples were enzymatically digested and cleaned up by solid-phase extraction before analysis. The adduct, a biomarker of chronic exposure over the preceding two to three months, was detected in nearly one-quarter of the women and 4 percent of the children with serum samples. Chronic aflatoxin exposure is linked to liver cancer, immune suppression, and child growth impairment, so its presence in a substantial fraction of reproductive-age women is a serious public health signal.

To translate blood concentrations into estimates of actual intake, the team calculated the probable daily intake, or PDI, for the most frequently detected toxins using toxicokinetic-based approaches. The results were alarming. The PDI of ochratoxin A exceeded health-based guidance values in 80 percent of the women and a striking 99 percent of the children. Citrinin intake was of concern for 12 percent of women and 27 percent of children. Children, with their lower body weight and developing organs, emerged as the most vulnerable group, absorbing comparable toxin burdens through smaller bodies and facing proportionally higher risks.

The study’s co-exposure findings add another layer of concern. Toxicology has traditionally assessed chemicals one at a time, yet mycotoxins frequently co-occur on the same food items because the fungi that produce them thrive under similar conditions of humidity, poor storage, and inadequate drying. OTA and citrinin, for instance, are often produced together by the same fungal species, and their combined kidney toxicity may be greater than either alone. With every participant carrying at least two mycotoxins and most carrying three or more, the realistic exposure scenario in rural Bangladesh is a complex toxicological cocktail whose interactions remain poorly understood.

Why is exposure so pervasive? In rural Bangladesh, maize, rice, wheat, and groundnuts are dietary staples, and these crops are highly susceptible to fungal contamination in the country’s hot, humid climate. Smallholder households often lack access to proper drying facilities, hermetic storage, or the means to sort and discard moldy grain. Food safety regulations, where they exist, are difficult to enforce in informal markets. As a result, mycotoxins enter the food supply at the farm level and travel directly to the family plate, with no practical means of avoidance for the households most affected.

The health implications extend beyond acute toxicity. Ochratoxin A is associated with chronic kidney disease and has been classified as possibly carcinogenic to humans. Aflatoxin B1 is a Group 1 human carcinogen that synergizes with hepatitis B infection to multiply liver cancer risk, a particularly worrying combination in regions where hepatitis B remains prevalent. Emerging toxins like enniatin B and beauvericin are only beginning to be characterized, and their long-term effects at chronic low doses are unknown. For children, chronic mycotoxin exposure has been linked in previous research to growth faltering, immune dysfunction, and reduced vaccine response—burdens that compound the already heavy challenges of malnutrition and infectious disease.

The authors emphasize that their findings demonstrate widespread co-exposure to multiple mycotoxins, with OTA, citrinin, and aflatoxin B1 posing notable risks, and they call for urgent, targeted interventions to protect vulnerable populations. Such interventions could include promoting improved post-harvest handling and drying practices, introducing hermetic storage bags that block fungal growth, supporting biocontrol agents that competitively exclude toxigenic fungi in the field, and strengthening food monitoring systems. Because blood biomonitoring captures actual internal exposure rather than estimated dietary intake, the approach used here could serve as a model for other low- and middle-income countries where mycotoxin contamination is suspected but poorly quantified.

The study also highlights the value of repurposing existing trial infrastructure for environmental health surveillance. By analyzing residual samples from the FAARM trial, the researchers obtained population-scale exposure data at a fraction of the cost of a dedicated biomonitoring campaign. As climate change expands the geographic range of toxigenic fungi and staple food systems come under increasing stress, the silent burden of mycotoxins documented in rural Bangladesh is likely a warning of what many other communities face. Making the invisible visible, this study suggests, is the first step toward reducing a health risk that has been simmering in the blood of millions for generations.

Subject of Research: Chronic blood-borne exposure to the mycotoxins aflatoxin B1, ochratoxin A, and citrinin among women and children in rural Bangladesh

Article Title: Chronic exposure to aflatoxin B1, ochratoxin A, and citrinin in women and children and associated health risk characterization: blood biomonitoring evidence from rural Bangladesh

Article References: Kyei, N. N. A., Cramer, B., Humpf, H.-U., Kuhn, M., Sobhan, S., Veerkamp, J., & Gabrysch, S. (2026). Chronic exposure to aflatoxin B1, ochratoxin A, and citrinin in women and children and associated health risk characterization: blood biomonitoring evidence from rural Bangladesh. Environmental Health, 25(1), Article 75. https://doi.org/10.1186/s12940-026-01330-7

Image Credits: AI Generated

DOI: 10.1186/s12940-026-01330-7

Keywords: mycotoxins, aflatoxin B1, ochratoxin A, citrinin, biomonitoring, Bangladesh, blood analysis, risk characterization, food safety, public health, children's health, UHPLC-MS/MS