Metagenome Analysis Identifies Microbial Shifts upon Deoxynivalenol Exposure and Post-Exposure Recovery in the Mouse Gut

Toxins · 5 authors, 3 centres

AI SUMMARY

FIDELITY 88%

POPULATION72 female BALB/c mice (6–7 weeks old, 20–22 g)

INTERVENTIONOral gavage of deoxynivalenol (DON) at 2 mg/kg bw/day (low dose) or 5 mg/kg bw/day (high dose) for 14 days

COMPARISONControl groups receiving purified water; recovery groups with either spontaneous recovery (standard diet) or inulin-supplemented diet (5% inulin) for 14 days post-exposure

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TL;DR

This study found that oral exposure to the mycotoxin deoxynivalenol (DON) at 2 or 5 mg/kg bw/day significantly alters the gut microbiome composition and function in mice, notably increasing Akkermansia muciniphila and decreasing beneficial butyrate-producing bacteria. Most microbiome changes reversed after a 2-week spontaneous recovery period, particularly in the low-dose group. Inulin supplementation aided recovery after low-dose DON exposure but paradoxically worsened dysbiosis after high-dose exposure, suggesting that prebiotic interventions may be harmful depending on the severity of toxin-induced disruption.

Full summary

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**Background:** Deoxynivalenol (DON) is a prevalent food-associated mycotoxin produced by Fusarium fungi that frequently contaminates cereals. Chronic exposure causes intestinal toxicity, immunotoxicity, and disrupts gut barrier function. While previous studies have shown DON alters gut microbiota composition, the functional consequences and post-exposure recovery dynamics—including the potential role of prebiotic interventions—remain poorly understood.

**Methods:** Seventy-two female BALB/c mice were assigned to 9 groups (n=8 each). Three groups received 14 days of: (1) purified water (CK1), (2) 2 mg/kg bw/day DON (LD1), or (3) 5 mg/kg bw/day DON (HD1). Six additional groups underwent 14 days of DON or water followed by 14 days of recovery: spontaneous recovery (CK2, LD2, HD2) or inulin-supplemented recovery (5% inulin in diet; CK3, LD3, HD3). Cecal contents were collected for metagenomic sequencing using Illumina HiSeq PE150. Taxonomic assignment used DIAMOND BLAST against NR database; functional annotation used KEGG (v2018.01), eggNOG (v4.5), and CAZy (v2018.01) databases. Statistical significance was assessed using two-sided unpaired Student's t-test or one-way ANOVA with p<0.05 considered significant.

**Key Results:** High-dose DON (5 mg/kg bw/day) significantly decreased body weight (p<0.05) and caused diarrhea, while low-dose DON did not affect weight. Metagenomic sequencing yielded 1,356,874 ORFs, with 87.0% annotated as bacterial. PCoA based on Bray-Curtis distance showed clear separation of high-dose DON groups from controls. DON exposure dose-dependently increased Verrucomicrobia (phylum level), with Akkermansia muciniphila showing significant increases in both LD1 and HD1 vs. CK1. At the species level, 841 species differed significantly between CK1 vs. LD1, and 969 between CK1 vs. HD1; 245 species were significantly changed in both. DON increased A. muciniphila, Bacteroides vulgatus, Hungatella hathewayi, and Lachnospiraceae bacterium 28-4, while decreasing Mucispirillum schaedleri, Pseudoflavonifractor sp. An85, Faecalibacterium prausnitzii, Firmicutes bacterium ASF500, Flavonifractor plautii, Oscillibacter sp. 1-3, and uncultured Flavonifractor sp. After 2 weeks of spontaneous recovery, only 138 of 841 (LD2) and 117 of 969 (HD2) species remained significantly different from controls, indicating ~86-88% recovery. Inulin supplementation after low-dose DON (LD3) resulted in only 54 of 841 species still significantly different vs. CK3, suggesting enhanced recovery. However, after high-dose DON with inulin (HD3), 651 of 969 species remained significantly different vs. CK3—substantially worse than spontaneous recovery. Gene numbers in HD3 were significantly reduced (p<0.01) compared to all other groups. Functional analysis showed that inulin supplementation normalized gene function after low-dose DON (no significant KEGG pathway differences between LD3 and CK3), but after high-dose DON, 31 functional gene clusters at KEGG level 2 remained significantly different in HD3 vs. CK3, compared to only 8 in HD2 vs. CK2.

**Clinical Implications:** This study demonstrates that DON-induced gut microbiome disruption is largely reversible upon toxin withdrawal, particularly at lower exposure levels. The finding that inulin—a commonly used prebiotic—exacerbates dysbiosis after high-dose DON exposure is clinically important, as it suggests that prebiotic interventions during recovery from severe mycotoxin exposure may be counterproductive. The dose-dependent increase in A. muciniphila, a mucin-degrading bacterium with known beneficial metabolic effects, may represent a compensatory host response to intestinal barrier damage. These findings highlight the need for careful evaluation of dietary interventions during gut microbiome recovery from toxic insults.

PICO

PPOPULATION

72 female BALB/c mice (6–7 weeks old, 20–22 g)

IINTERVENTION

Oral gavage of deoxynivalenol (DON) at 2 mg/kg bw/day (low dose) or 5 mg/kg bw/day (high dose) for 14 days

OOUTCOME

Changes in gut microbiome composition (taxonomic shifts at phylum, genus, and species levels), functional gene profiles (KEGG, eggNOG, CAZy), and body weight

STUDY TYPE

other

SPECIALTY

gastroenterology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

88% · B

ORIGINAL PAPER

PMC10142982

Metagenome Analysis Identifies Microbial Shifts upon Deoxynivalenol Exposure and Post-Exposure Recovery in the Mouse Gut

Toxins

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ABSTRACT

Deoxynivalenol (DON) is one of the most prevalent food-associated mycotoxins, and is known to cause a variety of adverse health effects on human and animals. Upon oral exposure, the intestine is the main target organ of DON. The current study unraveled that DON exposure (2 mg/kg bw/day or 5 mg/kg bw/day) can significantly reshape the gut microbiota in a mouse model. The study characterized the specific gut microbial strains and genes changed after DON exposure and also investigated the recovery of the microbiota upon either 2 weeks daily prebiotic inulin administration or 2 weeks recovery without intervention after termination of DON exposure (spontaneous recovery). The results obtained reveal that DON exposure causes a shift in gut microorganisms, increasing the relative abundance of Akkermansia muciniphila, Bacteroides vulgatus, Hungatella hathewayi, and Lachnospiraceae bacterium 28-4 , while the relative abundance of Mucispirillum schaedleri , Pseudoflavonifractor sp. An85 , Faecalibacterium prausnitzii , Firmicutes bacterium ASF500 , Flavonifractor plautii , Oscillibacter sp. 1-3 , and uncultured Flavonifractor sp. decreased. Notably, DON exposure enhanced the prevalence of A. muciniphila, a species considered as a potential prebiotic in previous studies. Most of the gut microbiome altered by DON in the low- and high-dose exposure groups recovered after 2 weeks of spontaneous recovery. Inulin administration appeared to promote the recovery of the gut microbiome and functional genes after low-dose DON exposure, but not after high-dose exposure, at which changes were exacerbated by inulin-supplemented recovery. The results obtained help to better understand the effect of DON on the gut microbiome, and the gut microbiota’s recovery upon termination of DON exposure.

CITATION EXPORT

Jing Jin, Chen Zhang, Xiaoxu Ren et al.. Metagenome Analysis Identifies Microbial Shifts upon Deoxynivalenol Exposure and Post-Exposure Recovery in the Mouse Gut. Toxins. (2023). https://doi.org/10.3390/toxins15040243

AUTHORS

5 · 3 CENTRES

Jing Jin, Chen Zhang, Xiaoxu Ren, Bowen Tai, Fuguo Xing

1Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs of China, 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China
2Division of Toxicology, Wageningen University and Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands
3Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands