Age-stratified models also placed the estimated margins of exposure for infants and young children far below the benchmark of 10,000 used to identify a public-health concern for a genotoxic carcinogen. These results come from a screening-level assessment that combined separate literatures rather than measuring feed and milk from the same Bangladeshi herds. The review assembled evidence from PubMed, Scopus, Web of Science and ScienceDirect for studies published from January 2000 through January 2026.

Of 318 records identified, 96 were removed as duplicates and 188 were excluded during title and abstract screening; 32 full texts were assessed, and 12 reports met the eligibility criteria. The 20 analysed datasets represented division-, site- or milk-type-specific strata within 10 distinguishable sources, including raw, pasteurised and ultra-high-temperature milk. Nine datasets were classified as being at low risk of bias, five at moderate risk and six at high risk.

All measurements used competitive enzyme-linked immunosorbent assay, or ELISA, and none was confirmed chromatographically. The investigators also prespecified subgroup analyses by region, milk type and risk of bias, along with sensitivity analyses intended to test whether clustered datasets, methodological choices or unusually high measurements altered the results. Aflatoxin B1 is the most prevalent aflatoxin congener in food and feed and the most potent naturally occurring hepatocarcinogen, according to the source article.

When lactating animals consume aflatoxin B1-contaminated feed, hepatic cytochrome-P450 hydroxylation converts part of the toxin to aflatoxin M1, which is secreted into milk. Aflatoxin M1 retains about one-tenth of the carcinogenic potency of its parent compound but resists pasteurisation and ultra-high-temperature processing, allowing it to remain in milk after those treatments. Bangladesh’s tropical monsoon climate supports fungal growth during crop filling, harvest and on-farm storage, while maize, a cereal particularly susceptible to aflatoxigenic fungi, is now a principal energy ingredient in compound feed.

The country’s expanding dairy sector remains dominated by smallholder and informal supply chains with limited cold-chain infrastructure, fragmented quality control and weak enforcement. Although aflatoxin also contaminates rice and other foods, the assessment focused on the milk pathway and did not estimate dietary exposure from those additional sources. The pooled concentration distribution was strongly right-skewed, making the choice of central measure important.

The sample-weighted arithmetic mean across datasets was 143 nanograms per litre, the sample-weighted geometric mean was 92 nanograms per litre, the median of dataset means was 88 nanograms per litre and the unweighted mean was 118 nanograms per litre. Typical regional raw-milk means ranged from 35 to 120 nanograms per litre, but one Dhaka dataset reported a mean of 699.1 nanograms per litre. Removing that single dataset, which represented 8% of all samples, reduced the weighted mean to 93 nanograms per litre, a 35% decrease.

The interquartile range of dataset means was 57 to 111 nanograms per litre, whereas the complete range extended from 6.6 to 699.1 nanograms per litre. Prevalence and mean concentration were largely decoupled: two datasets with 100% positivity had among the lowest means, and the highest concentration occurred at a prevalence close to the pooled value. The assessment therefore relied on the concentration distribution rather than treating the proportion of positive samples as a sufficient measure of exposure.

Milk type did not significantly explain differences in prevalence, whereas region did. Raw milk had a pooled prevalence of 60.4%, compared with 59.0% in pasteurised milk and 69.5% in ultra-high-temperature milk, but the between-subgroup test found no significant difference among the three categories. The ultra-high-temperature estimate was not considered interpretable because it was based on only two datasets, one reporting 20% positivity and the other 100%, and its prediction interval spanned the complete possible range.

Region showed a more consistent pattern: prevalence was 43.7% in Chattogram, 55.3% in Dhaka and 66.8% across other divisions and national samples, with a Q-between value of 13.5, two degrees of freedom and a nominal p value of 0.001. This was the only pre-specified subgroup comparison to remain significant after Holm adjustment, with an adjusted p value of 0.004, although the authors classified it as hypothesis-generating rather than an established geographic gradient. Residual heterogeneity was also 21% to 23% in exploratory one-covariate meta-regressions, leaving variation potentially associated with unmeasured differences in season, analytical kit, detection threshold, sampling frame and position within the supply chain.

The feed evidence showed that the upstream contamination burden was compatible with the milk observations, but it did not establish a causal relationship within Bangladesh. Published surveys reported aflatoxin B1 at 0 to 160 micrograms per kilogram in poultry feed and 1 to 103 micrograms per kilogram in maize, with both matrices frequently exceeding the 20 micrograms per kilogram general feed maximum. Compound beef-cattle feed ranged from 7.78 to 14.66 micrograms per kilogram, while oil cakes, bran, rice straw and soybean meal had means of approximately 9.8 to 12 micrograms per kilogram.

Although many cattle-feed means remained below 20 micrograms per kilogram, they exceeded the European Union limit of 5 micrograms per kilogram for dairy-cattle feed. Maize and other feed ingredients also contained fumonisins, zearalenone and sterigmatocystin, revealing a multi-mycotoxin burden not captured by the aflatoxin-specific risk metrics. Feed and milk measurements both showed a June-to-August maximum, consistent with a humidity-driven mechanism, but the series came from independent studies, sites and years and therefore did not demonstrate coupling within a shared production system.

For the mechanistic check, the researchers transferred a published yield-dependent carry-over function from controlled trials of 12 high-yielding Israeli-Holstein cows to three ration scenarios representing Bangladeshi smallholder practice. The function predicted transfer of approximately 0.67% to 1.13% at milk yields of 5 to 15 kilograms per day, with reconstructed milk concentrations spanning 24 to 282 nanograms per litre and a central prediction of 80 nanograms per litre. That envelope contained 18 of the 20 observed dataset means, or 90%, and the central prediction was close to the observed geometric mean of 92 nanograms per litre.

Reproducing the sample-weighted mean of 143 nanograms per litre required a ration-weighted aflatoxin B1 concentration of about 18 micrograms per kilogram, while reproducing the extreme Dhaka mean would have required about 89 micrograms per kilogram. The two tails, at 6.6 and 699.1 nanograms per litre, lay outside the envelope. This result shows that the independent feed and milk literatures were quantitatively compatible under the transferred model; it does not show that a particular feed sample caused a particular milk residue.

Moreover, the carry-over relationship was extrapolated below the 30-to-46-kilogram daily-yield range represented in its original calibration. Using Bangladesh-specific milk-intake and body-weight parameters, the central scenario estimated aflatoxin M1 exposure at 4.22 nanograms per kilogram of body weight per day for infants aged 0.5 to 1 year, 2.29 for toddlers aged 1 to 3 years, 1.08 for children aged 4 to 9 years, 0.38 for adolescents aged 10 to 17 years and 0.24 for adults aged 18 years or older. Corresponding margins of exposure were 95, 175, 372, 1,055 and 1,649, all below the benchmark of 10,000, while hazard indices were 21.1, 11.4, 5.4, 1.9 and 1.2, all above one.

Under a high-concentration scenario of 250 nanograms per litre, the infant margin fell to 54. The central model estimated incremental hepatocellular carcinoma incidence of 0.0108 cases per 100,000 infants per year, rising to 0.0189 in the high scenario. These cancer estimates were order-of-magnitude indicators rather than case counts because they depended on an aflatoxin M1 relative potency factor of 0.1 and an HBsAg-weighted potency model using an approximately 5.4% hepatitis-B surface antigen carrier prevalence.

A 100,000-iteration Monte Carlo simulation incorporated variability in milk concentration, intake and body weight, treating the three inputs as independent. Median margins of exposure were 157 for infants, 286 for toddlers, 612 for children, 1,720 for adolescents and 2,735 for adults; fifth-percentile values were 30, 55, 119, 340 and 543, respectively. The simulation produced a margin below 10,000 in 100% of infant and toddler iterations, 99.7% of child iterations, 96.2% of adolescent iterations and 90.4% of adult iterations.

For infants, 32.8% of iterations produced a margin below 100, while the median hazard index was 12.8 for infants, 7.0 for toddlers, 3.3 for children, 1.2 for adolescents and 0.7 for adults. These probabilistic medians were higher than the deterministic margins because the fitted concentration distribution was centred on the 92 nanogram per litre geometric mean rather than the 143 nanogram per litre arithmetic mean. The numerical exposure estimates therefore varied with the central tendency used, but the principal conclusion remained stable: no tested scenario or restriction raised the infant margin above 158, at least 60-fold below the 10,000 benchmark.

Several limitations constrain the assessment. All included measurements relied on competitive ELISA without chromatographic confirmation, and inconsistent reporting of detection limits, recovery and within-dataset concentration distributions prevented the investigators from reconstructing individual exposures. Most surveys used convenience samples from markets, collection points or farms rather than probability samples of the national milk supply.

Six datasets had uncertain provenance or a high risk of bias, and four reports contributed multiple strata, so the 20 datasets did not represent 20 fully independent sources. A 50% downward correction for possible ELISA overestimation reduced the weighted concentration to 96 nanograms per litre but left the infant margin at 142. Restricting the evidence to fully referenced peer-reviewed datasets produced a weighted mean of 172 nanograms per litre and an infant margin of 79, while removing the influential Dhaka dataset produced a mean of 93 nanograms per litre and a margin of 146.

Alternative heterogeneity estimators left pooled prevalence between 58.7% and 59.0%, and no plausible single uncertainty or tested combination reversed the finding. The authors identified paired feed-and-milk sampling from the same herds across monsoon and dry seasons, chromatographic confirmation, individual milk-consumption data and replication of the high-concentration Dhaka milk shed as priorities for converting this literature-based screening assessment into a more precise national exposure model.

Subject of Research: Systematic review and meta-analysis of aflatoxin contamination in Bangladeshi milk and animal feed, with modelled dietary risk by age.

Article Title: Aflatoxin M1 in Milk and Aflatoxin B1 in Animal Feed in Bangladesh: A Systematic Review, Meta‐Analysis and Literature‐Based Dietary Risk Assessment

Article References: Fattah, M. A., & Habib, M. A. (2026). Aflatoxin M 1 in Milk and Aflatoxin B 1 in Animal Feed in Bangladesh: A Systematic Review, Meta‐Analysis and Literature‐Based Dietary Risk Assessment. Veterinary Medicine and Science, 12(6), Article e71284. https://doi.org/10.1002/vms3.71284

Image Credits: AI Generated

DOI: 10.1002/vms3.71284

Keywords: aflatoxin M1, aflatoxin B1, Bangladesh, milk contamination, animal feed, food safety, dietary exposure, infant nutrition, hepatocellular carcinoma, meta-analysis, Aflatoxin, Milk

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

Aflatoxin B1 is not a minor agricultural nuisance. Produced by Aspergillus flavus and its close relative Aspergillus parasiticus, the compound routinely contaminates maize, peanuts, tree nuts, and other commodities, and chronic dietary exposure is strongly linked to hepatocellular carcinoma, particularly in regions where food security infrastructure is limited. Regulatory agencies worldwide enforce strict limits on aflatoxin levels in food and feed, yet controlling the fungus in the field and during storage remains an uphill battle. Understanding the internal circuitry that switches toxin production on and off has therefore been a central goal of mycotoxin research for decades, and the new study adds a critical piece to that puzzle: the fungus appears to read its iron environment through AflHapX and adjust its toxin output accordingly.

The team began by searching the A. flavus genome using the protein sequence of HapX from Aspergillus fumigatus, a well-characterized iron regulator in that pathogenic mold. This bioinformatic fishing expedition pulled out AflHapX, a bZIP-type transcription factor belonging to a family of proteins that bind DNA through a basic leucine zipper domain. To determine what the gene actually does, the researchers turned to homologous recombination, a technique that allows precise replacement of a target gene with a selectable marker. Using this approach, they constructed a deletion strain lacking AflhapX, as well as a complemented strain in which the gene was restored. This trio of strains, wild type, deletion mutant, and complemented control, forms the gold-standard experimental design for establishing that an observed phenotype is genuinely caused by the gene in question rather than by off-target effects of the genetic manipulation.

The first major result concerned aflatoxin production under standard laboratory conditions. When equal numbers of spores, or conidia, from the three strains were inoculated onto YES medium and incubated for seven days at 29 degrees Celsius, the deletion mutant produced significantly less aflatoxin B1 than both the wild type and the complemented strain, as measured by thin-layer chromatography. This straightforward observation established AflHapX as a positive regulator of toxin biosynthesis. But the more striking discovery came when the researchers manipulated iron availability in the culture environment, growing the wild-type and mutant strains under iron-sufficient, iron-starved, and iron-excess conditions and comparing toxin output across all six combinations.

The pattern that emerged was anything but simple. In the deletion mutant, aflatoxin B1 production was highest under iron excess, intermediate under iron sufficiency, and lowest under iron starvation. The wild type showed precisely the opposite relationship, producing more toxin when iron was scarce and less when iron was abundant. In other words, removing AflHapX inverted the fungus’s iron-to-toxin relationship, a result that strongly suggests the transcription factor is the conduit through which iron availability is translated into changes in aflatoxin biosynthesis. The authors conclude that AflHapX regulates AFB1 production through the iron homeostasis pathway, effectively coupling a fundamental nutrient-sensing system to a virulence and contamination trait of enormous economic and public health importance.

Iron is a double-edged nutrient for fungi. It is essential as a cofactor for enzymes involved in respiration, DNA synthesis, and detoxification, yet excess iron catalyzes the formation of destructive hydroxyl radicals through the Fenton reaction. Filamentous fungi therefore maintain elaborate iron regulatory networks, and in Aspergillus species the HapX protein sits at the center of that network, working with the CCAAT-binding complex to repress or activate genes depending on whether iron is scarce or plentiful. The new study demonstrates that in A. flavus this ancient homeostatic machinery does not merely manage iron metabolism; it also feeds into the regulation of secondary metabolism, the branch of fungal chemistry responsible for aflatoxins and numerous other bioactive compounds.

Beyond toxin production, the deletion of AflhapX produced a constellation of other phenotypes that flesh out the protein’s biological role. Mutant strains formed more sclerotia, the compact survival structures that A. flavus uses to persist in soil and overwinter between cropping seasons, hinting that iron signaling may also influence the fungus’s environmental survival strategy. The mutant was also markedly more sensitive to oxidative stress reagents, including hydrogen peroxide, menadione sodium bisulfite, and diamide, indicating that AflHapX helps the fungus cope with reactive oxygen species. This connection is particularly intriguing because oxidative stress is known to influence aflatoxin biosynthesis, and because the host plant itself generates oxidative bursts as a defense against fungal invasion.

To move from single-gene observations to a genome-wide picture, the team performed RNA sequencing on the wild-type and deletion strains. The transcriptome data revealed that AflHapX acts globally at the transcriptional level, coordinating the expression of genes involved in iron homeostasis, aflatoxin biosynthesis, and oxidative stress responses. This systems-level view confirms that the phenotypes observed in the plate assays reflect broad transcriptional rewiring rather than isolated changes, and it provides a catalog of downstream targets that other laboratories can now mine for additional regulatory connections.

The practical significance of the work was tested on the crop itself. When the wild-type, deletion, and complemented strains were inoculated onto peanut seeds, the deletion mutant produced fewer conidia and less aflatoxin B1 than the other two strains. Peanuts are among the crops most vulnerable to A. flavus infection, and the reduced growth and toxin output of the mutant on seeds suggests that AflHapX contributes to the fungus’s fitness in its natural agricultural niche, not just under laboratory conditions.

Professor Wang summarized the implications, stating that the findings demonstrate AflHapX serves as a key regulator coupling iron availability and aflatoxin B1 biosynthesis in A. flavus, and that the study provides new insights into the interplay between environmental iron and mycotoxin production, with potential implications for understanding the regulatory mechanisms of aflatoxin contamination in agricultural products. The prospect of targeting an iron-sensing pathway to suppress toxin production opens a genuinely novel intervention strategy. Iron availability in stored grain and processed commodities is an environmental variable that could, in principle, be managed through storage practices, biofortification approaches, or the development of compounds that disrupt AflHapX function. Because the deletion mutant also shows reduced sporulation on seeds, interfering with this pathway might simultaneously limit both the spread of the fungus and its chemical arsenal. The research also raises questions that extend well beyond a single species: if nutrient sensing and secondary metabolism are cross-wired in A. flavus, similar regulatory couplings may operate in other pathogenic and toxigenic fungi worldwide, offering a general principle for future antifungal and antitoxin strategies.

Subject of Research: Iron homeostasis and aflatoxin biosynthesis regulation by the transcription factor AflHapX in Aspergillus flavus

Article Title: bZIP transcription factor AflHapX coordinates iron homeostasis and aflatoxin biosynthesis in Aspergillus flavus

Article References: bZIP transcription factor AflHapX coordinates iron homeostasis and aflatoxin biosynthesis in Aspergillus flavus. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Aspergillus flavus, AflHapX, aflatoxin B1, iron homeostasis, bZIP transcription factor, mycotoxin, transcriptomics, oxidative stress, sclerotia, peanut contamination, food safety, fungal biology

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

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