The Hidden Threat: How Mycotoxins Damage the Gut-Brain Axis in Livestock

Introduction

The intestine is the first line of defense -- and the first point of contact -- when livestock consume mycotoxin-contaminated feed. For decades, the scientific community has studied how these toxins damage the intestinal epithelium. But a new area of research reveals an even more disturbing picture: mycotoxins may be damaging the enteric nervous system (ENS) -- the "brain in the gut" -- at concentrations previously considered safe.

A landmark peer-reviewed study published in Toxins journal (Dabrowski et al., 2025) tested eighteen major mycotoxins -- both regulated and non-regulated -- on enteric glial cells (EGCs), the cells that control gut motility, barrier integrity, and immune response. The results were striking: twelve of the eighteen mycotoxins tested showed toxic effects on EGCs, many at concentrations achievable through normal feed consumption.

What Are Enteric Glial Cells and Why Do They Matter?

Enteric glial cells (EGCs) form a network of nerve cells embedded in the wall of the gastrointestinal tract. They are not just "support cells" -- they are active regulators of:

• Intestinal barrier integrity -- EGCs maintain the tight junctions between intestinal epithelial cells, preventing pathogens and toxins from entering the bloodstream
• Gut motility -- EGCs coordinate muscle contractions along the digestive tract
• Immune function -- EGCs modulate the gut-associated lymphoid tissue (GALT) response
• Inflammatory responses -- EGCs communicate with both the immune system and the central nervous system

When EGCs are damaged, the consequences extend beyond the gut: impaired nutrient absorption, increased susceptibility to pathogens, chronic low-grade inflammation, and reduced feed efficiency. In production animals, this translates directly into poorer FCR, reduced weight gain, and economic losses that are often misattributed to other causes.

The Study: 18 Mycotoxins Tested on Living Gut Cells

Researchers from Aix Marseille University, INRAE Toulouse, and the University of Warmia and Mazury exposed rat EGCs to increasing concentrations of eighteen major mycotoxins -- both regulated and non-regulated. They measured:

• IC₅₀ (antiproliferative): the concentration at which a mycotoxin reduces cell division by 50%
• CC₅₀ (cytotoxic): the concentration at which a mycotoxin reduces cell viability by 50%

The mycotoxins tested included the six regulated toxins (AFB1, DON, FB1, OTA, PAT, ZEN) and twelve non-regulated or "emerging" mycotoxins (enniatins, beauvericin, apicidin, emodin, and others).

Key Findings: Which Mycotoxins Damage the Gut-Brain Axis?

Regulated Mycotoxins

Mycotoxin	IC50 on EGC Proliferation (uM)	CC50 on EGC Viability (uM)
Deoxynivalenol (DON)	0.19 +/- 0.07	5.06 +/- 0.48
Patulin	9.19 +/- 0.96	38.02 +/- 11.37
Ochratoxin A	13.79 +/- 1.13	23.88 +/- 1.36
Aflatoxin B1	>100	>100
Fumonisin B1	>100	>100
Zearalenone	>100	31.75 +/- 4.94

DON was the most toxic among regulated mycotoxins, causing EGC damage at concentrations as low as 0.19 uM -- a level that can be reached in the gut during normal consumption of contaminated feed.

Non-Regulated / Emerging Mycotoxins

Mycotoxin	IC50 on EGC Proliferation (uM)	CC50 on EGC Viability (uM)
Enniatin B1	0.92 +/- 1.07	0.72 +/- 0.16
Enniatin A	0.93 +/- 0.13	1.05 +/- 0.11
Enniatin A1	1.08 +/- 0.34	0.86 +/- 0.09
Enniatin B	1.40 +/- 0.18	2.14 +/- 0.17
Beauvericin	1.41 +/- 0.20	1.91 +/- 0.45
Apicidin	1.63 +/- 0.21	59.59 +/- 10.27
Emodin	40.01 +/- 2.70	>100
Aurofusarin	79.51 +/- 3.68	>100

Enniatins and beauvericin -- non-regulated mycotoxins produced by Fusarium fungi -- were among the most toxic compounds tested, damaging EGCs at concentrations between 0.72 and 1.41 uM.

The Implications for Livestock Production

The gastrointestinal concentration of mycotoxins in the gut lumen can reach levels far higher than those found in blood. When the research team calculated realistic gut concentrations based on NOAEL/LOAEL values:

• DON was found at toxic levels in the gut at concentrations below levels previously considered safe
• Enniatins and beauvericin showed toxicity at concentrations achievable through normal feed consumption

What this means in practice:

1. DON and emerging mycotoxins damage the ENS at realistic feed contamination levels
2. Non-regulated mycotoxins (enniatins, beauvericin) may be causing EGC damage that is currently going unrecognized -- because standard mycotoxin tests do not always screen for them
3. The gut-brain axis is a genuine target of mycotoxin toxicity -- not just the liver, kidneys, and immune system
4. Animals showing poor FCR without clear pathogen cause may be suffering from subclinical mycotoxin effects on the ENS and gut barrier

Mechanisms of Damage

The study identified three pathways through which mycotoxins damage EGCs:

1. Oxidative stress -- mycotoxins generate reactive oxygen species (ROS) that damage EGC membranes and DNA
2. Membrane integrity alteration -- direct disruption of cell membrane function
3. Apoptosis -- programmed cell death triggered at specific concentration thresholds

Why Current Risk Assessments May Be Incomplete

Current EU mycotoxin regulations are based primarily on effects on liver, kidney, and immune function. This study suggests the gut nervous system may be a more sensitive indicator of mycotoxin toxicity -- and one that is currently overlooked in feed safety assessments.

For livestock producers, this means:

• Feed testing panels that only cover the 6 regulated mycotoxins may miss the most damaging emerging toxins
• The real economic impact of mycotoxins on gut health and feed efficiency may be significantly underestimated
• A holistic mycotoxin risk management strategy -- covering both regulated AND non-regulated toxins -- may deliver greater returns than previously assumed

Practical Implications for Feed Mills and Producers

Based on this research, the following actions can reduce mycotoxin-related losses:

1. Expand testing panels to include emerging mycotoxins -- enniatins, beauvericin, apicidin
2. Use broad-spectrum mycotoxin binders that are effective against both regulated toxins (DON, OTA, AFB1) AND emerging toxins (enniatins, beauvericin)
3. Consider gut health parameters when diagnosing unexplained FCR issues -- EGC damage may be a contributing factor
4. Implement feed hygiene protocols at storage and mixing stages to reduce Fusarium proliferation

Conclusion

This peer-reviewed study provides the first evidence that enteric glial cells -- the master regulators of gut barrier function and gut-brain communication -- are direct targets of both regulated and non-regulated mycotoxins, at concentrations achievable through normal feed consumption.

For the livestock industry, this is both a warning and an opportunity: the warning is that current mycotoxin risk management may be incomplete. The opportunity is that addressing the full spectrum of mycotoxin risk -- including emerging toxins -- can deliver measurable improvements in gut health, feed efficiency, and animal performance.

This article is based on peer-reviewed research published in Toxins journal. Dabrowski et al. (2025). Impact of Regulated and Non-Regulated Food-Associated Mycotoxins on the Viability and Proliferation of Enteric Glial Cells. Toxins, 17, 587. https://doi.org/10.3390/toxins17120587