Mycotoxins are fungal metabolites that occur in human foods and animal feeds, potentially threatening human and animal health. The intestine is considered as the first barrier against these external contaminants, and it consists of interconnected physical, chemical, immunological, and microbial barriers. In this context, based on in vitro, ex vivo, and in vivo models, we summarize the literature for compromised intestinal barrier issues caused by various mycotoxins, and we reviewed events related to disrupted intestinal integrity (physical barrier), thinned mucus layer (chemical barrier), imbalanced inflammatory factors (immunological barrier), and dysfunctional bacterial homeostasis (microbial barrier). We also provide important information on deoxynivalenol, a leading mycotoxin implicated in intestinal dysfunction, and other adverse intestinal effects induced by other mycotoxins, including aflatoxins and ochratoxin A. In addition, intestinal perturbations caused by mycotoxins may also contribute to the development of mycotoxicosis, including human chronic intestinal inflammatory diseases. Therefore, we provide a clear understanding of compromised intestinal barrier induced by mycotoxins, with a view to potentially develop innovative strategies to prevent and treat mycotoxicosis. In addition, because of increased combinatorial interactions between mycotoxins, we explore the interactive effects of multiple mycotoxins in this review.

With the growing diversity and complexity of diet, humans are at risk of simultaneous exposure to aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1), which are well-known contaminants in dairy and other agricultural products worldwide. The intestine represents the first barrier against external contaminants; however, evidence about the combined effect of AFB1 and AFM1 on intestinal integrity is lacking. In vivo, the serum biochemical parameters related to intestinal barrier function, ratio of villus height/crypt depth, and distribution pattern of claudin-1 and zonula occluden-1 were significantly affected in mice exposed to 0.3 mg/kg b.w. AFB1 and 3.0 mg/kg b.w. AFM1. In vitro results on differentiated Caco-2 cells showed that individual and combined AFB1 (0.5 and 4 μg/mL) and AFM1 (0.5 and 4 μg/mL) decreased cell viability and trans-epithelial electrical resistance values as well as increased paracellular permeability of fluorescein isothiocyanate-dextran in a dose-dependent manner. Furthermore, AFM1 aggravated AFB1-induced compromised intestinal barrier, as demonstrated by the down-regulation of tight junction proteins and their redistribution, particularly internalization. Adding the inhibitor chlorpromazine illustrated that clathrin-mediated endocytosis partially contributed to the compromised intestinal integrity. Synergistic and additive effects were the predominant interactions, suggesting that these toxins are likely to have negative effects on human health.

Milk authentication requires identification of the origin and assessment of the aroma characteristics. In this study, we analyzed 24 raw milk samples from different regions of China by profiling volatile flavors using headspace solid phase microextraction-gas chromatography-mass spectrometry, headspace gas chromatography-ion mobility spectrometry, and intelligent sensory technology (E-tongue and E-nose). The flavor of raw milk in Southern and Northern China had evident differences based on the intelligent sensory technology. However, the differences among the samples from the northeast, northwest, and central regions were not significant. Correlations between milk origin and volatile compounds based on variable importance prediction > 1 and principal component analysis results revealed differential compounds including pyridine, nonanal, dodecane, furfural, 1-decene, octanoic acid, and 1,3,5,7-cyclooctatetraene. Our study findings provided a deeper understanding of the geographical differences in raw milk volatile compounds in China.

In order to analyze the influence of key additives during processing on the flavor of infant formula, the headspace-gas chromatography-ion mobility spectrometry, electronic tongue, and electronic nose techniques were used to evaluate flavor during the processing of stage 1 infant formula milk powder (0–6 months), including the analysis of seven critical additives. A total of 41 volatile compounds were identified, involving 12 aldehydes, 11 ketones, 9 esters, 4 olefins, 2 alcohols, 2 furans, and 1 acid. The electronic nose metal oxide sensor W5S had the highest response, followed by W1S and W2S, illustrating that these three sensors had great effects on distinguishing samples. The response results of the electronic tongue showed that the three sensory attributes of bitter, salty, and umami, as well as the richness of aftertaste, were more prominent, which contributed significantly to evaluating the taste profile and distinguishing among samples. Raw milk is an essential control point in the flavor formation process of stage 1 infant formula milk powder. Demineralized whey powder is the primary source of potential off-flavor components in hydrolyzed milk protein infant formula. This study revealed the quality characteristics and flavor differences of key additives in the production process of stage 1 infant formula milk powder, which could provide theoretical guidance for the quality control and sensory improvement of the industrialized production of infant formula.

Antibiotics are frequently used to treat dairy cows with mastitis. However, the potential effects of β-lactam antibiotics, such as cephalosporins, on the fecal microbiome is unknown. The objective was to investigate the effects of ceftiofur and cefquinome on the fecal microbiota and antibiotic resistance genes of dairy cows with mastitis. The fecal samples were collected from 8 dairy cows at the following periods: the start day (Day 0), medication (Days 1, 2, and 3), withdrawal (Days 4, 6, 7, and 8), and recovery (Days 9, 11, 13, and 15). 16S rRNA gene sequencing was applied to explore the changes in microbiota, and qPCR was used to investigate the antibiotic resistance genes. The cephalosporin treatment significantly decreased the microbial diversity and richness, indicated by the decreased Shannon and Chao 1 indexes, respectively (p < 0.05). The relative abundance of Bacteroides, Bacteroidaceae, Bacteroidales, and Bacteroidia increased, and the relative abundance of Clostridia, Clostridiales, Ethanoligenens, and Clostridium IV decreased at the withdrawal period. The cephalosporin treatment increased the relative abundance of β-lactam resistance genes (bla_TEM and cfxA) at the withdrawal period (p < 0.05). In conclusion, the cephalosporin treatment decreased the microbial diversity and richness at the medication period, and increased the relative abundance of two β-lactam resistance genes at the withdrawal period.

Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25–20 μM) and AFM1 (5–20 μM) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 μM) and AFM1 (2.5 μM) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.