Friday, 27 August 2010

Increasing Levels of Mycotoxins in Animal Feed

Mycotoxins in our food is not something people in the developed world hear much about. We have our basic food hygiene and a natural innate distaste for eating mouldy food that protects us, and we have a rigid food testing regime that ensures we do not have significant mycotoxin contamination of the foods we buy from producers. But how much are we exposed to and how often?

Bearing in mind that foodstuffs intended for animals are of a lower quality than food intended for human consumption, so mycotoxin prevalence is far more likely to be widespread, this survey is still quite striking. Also bear in mind that the company undertaking this survey seem to be involved in providing mycotoxin management services to the producer, so do have a vested interest in emphasising the positive!

There are five toxin groups surveyed; aflatoxins (Afla), zearalenone (ZON), deoxynivalenol (DON), fumonisins (FUM) and ochratoxin A (OTA) which are produced in the main by three different fungi; Aspergillus, Penicillium and Fusarium. Most strikingly the number of samples testing as positive (see map for regional variations) vary from 28% (OTA) to 56% (FUM) - a very large proportion, leading to the natural conclusion that most food animals are feeding on mycotoxins most of the time. The terms of reference for the producer are of course how this would impact the wellbeing of his stock animals, there is no attempt to record the levels of mycotoxin in the resulting meat & other products in this survey.

NB Mycotoxin levels in food derived from animals is strictly controlled throughout the developed world - see, so we could conclude that although animal feeds are frequently contaminated by mycotoxins, those mycotoxins are not passed down through the food chain to us at levels thought to do us harm. The safe levels set seem to be largely based on tests on laboratory animals eating large amounts of toxin and laboratory experiments on human cell lines- see toxicology.

It is also mentioned in this survey that more than one mycotoxin was found in many samples, and it is implied that this may well increase the harm to the stock, though no evidence is referred to to back this up. This is a poorly understood subject for both animal and human food.

Chronic low level exposure to mycotoxins is starting to be defined on an international scale, cheap, consistent testing is being developed and international regulations harmonised. There are some reports of health problems (link) but this is still a poorly understood area of some concern (link).

Overall the levels of mycotoxins we are exposed to in our food is under strict control in developed countries, but there are still poorly defined risks with serious difficulties tracing the results of an exposure that might not emerge until several years later. We cannot regulate our own exposure on a personal level as we cannot know what foods we eat contain mycotoxins, all we know is that some are likely to contain mycotoxins at low levels  and that as far as we can tell there are no major health effects from eating our food. Much more research is needed to define these risks.

Monday, 23 August 2010

Steps to Proving Inhaled Mycotoxins are Harmful to Human Health?

This fierce debate has raged for some years now and shows few signs of abating, but as both sides of the argument have much to lose that isn't too much of a surprise.

Recent events in Africa have illustrated the dreadful consequences of  mycotoxin getting into food, but these levels are far more strictly controlled in the developed parts of the world such as EU & USA, not least because food storage conditions are much better controlled.

The home & work environment is a different matter. Major floods cause massive damage to property and leave what is left standing very wet & mouldy. The occupants often have no choice but to carry on living in their damaged houses and thus are forced to breathe in air inevitably charged with mould spores.
There are of course many more buildings that become contaminated by moulds without the need for huge natural disasters - a simple unattended pipe leak can cause the growth of a lot of mould in a few days. Moulds need no light to grow (are in fact inhibited by light) so there are many examples of moulds growing in closed appliances such as air conditioning units and consequently causing lots of mould spores to be released into the air.

The difficulty lies in assessing whether or not the spores being breathed in are causing health problems. One part of the debate is fairly clear - the breathing in of mould spores can trigger allergies and can do it over a very long time if the source of the mould remains undetected. These allergies can trigger more serious health problems such as asthma, particularly amongst children - damp, mouldy homes are proven to be bad for our health.

What about mycotoxin toxicity? Toxins cause problems to health depending on how much enters the body of the victim i.e. toxicity is dose dependant. A fair amount is known about what dose causes health problems when food is contaminated, but this is generally based on acute outbreaks of mycotoxicity when people or animals eat heavily contaminated food for a relatively short time. The people at risk often have no other food to eat so do tend to get high doses.

What is a safe amount to eat, given that even in the developed world it is virtually impossible to totally eliminate mycotoxins from our diet? (Some enlightening UK figures here).
The various national and international authorities set 'safe limits' for food and animal feed based on individual toxin levels.
Small amounts are thought to have minimal effect as they are usually quickly removed by our livers (all of us will be being exposed to low or very low levels of toxins in our food), but what about continued chronic inhalation of low amounts of several different types of toxin every day- a scenario that is quite likely in a damp building?

The debate comes down to the accumulation of  toxins in tissues. Much has been written about what dose a person living in a building would get by breathing in spores, rudimentary calculations have been done on the number of spores they need to inhale and how likely it would be that they could inhale that amount under reasonable circumstances but little of the resulting data is robust. Perhaps it is better to measure the amount of mycotoxin in the different tissues of each person exposed and thus get a direct idea of the level of their exposure? That is exactly what the researchers in this paper have set out to do.

Hooper have demonstrated that is it possible to detect several different mycotoxins in samples taken from patients known to have been exposed to mould (though they don't say what their criteria for this were) and to determine the amount of each mycotoxin in each sample. The techniques are simple adaptions of current technology so should be widely applicable. The amounts measured are correlated with reported clinical signs of illness, though most seem to be quite vague..

Amounts measured for each mycotoxin (trichothecenes, aflatoxins, and ochratoxins) tested in urine in this paper seem to be of the order of 0.2 to >2 parts per billlion which equates to 0.2 to >2 microgrammes per litre. Assuming a litre of urine produced per person per day that could be 0.2 to >2 microgrammes per day.

If we look at ochratoxin levels in the urine of normal healthy people in this paper we find up to 0.025 microgramme per litre per day - ten to a hundred fold less than that in people exposed to mould in the previous paper.

If this study is borne out we now seem to have some of the tools needed to directly measure exposure to mycotoxins in the body tissues of people exposed to moulds in their environment. Further studies will  be needed to determine the effects of that exposure on human health and what factors in low level chronic exposure are important - e.g. current dose, total cumulative dose, length of exposure, which mycotoxin or combination of mycotoxins has worst effects.

Tuesday, 17 August 2010

Vitamin D could be used to treat ABPA in Cystic Fibrosis?

A research paper due to be published in September 2010 reports the observation that some patients who have Cystic Fibrosis (CF) are prone to becoming infected with Aspergillus fumigatus and then developing Allergic Bronchopulmonary Aspergillosis (ABPA - Wiki) while others are infected but do not go on to develop ABPA.

Entitled 'Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis' the research focusses on finding differences between these two types of CF patient and one of the differences noted was the lower concentration of vitamin D in the blood of patients who suffered from ABPA. In other words most patients who had ABPA also had lower levels of vitamin D.
This observation leads to an obvious next step - what happens if you increase the blood levels of vitamin D in those patients? More specifically what happens to their ABPA? That question is now open, hopefully the subject of a clinical trial and we will know the answer in due course however we have had a hint at the answer in the next part of this paper.

Some of the major symptoms of ABPA are essentially the result of an over-response to the presence of Aspergillus by part of the immune system known as Th2 - part of the inflammatory response pathway that caused inflammation when we injure ourselves of become infected.
The group carrying out this research have set up a laboratory 'model system' whereby cells from each type of patient were isolated and grown in culture. They can then be stimulated to induce the Th2 'inflammatory' signalling pathway and their response noted. The result was that those cells taken from patients with ABPA responded by initiating inflammation whereas those taken from non-ABPA patients did not respond. Intriguingly we now have a result that parallels the clinical observation that cells in the airways of ABPA-CF patients respond to stimulation by Aspergillus by becoming inflamed whereas the non-ABPA-CF patients cells do not repond.

What happens if you add in vitamin D to each culture in the laboratory? Now cells from both types of patients do not respond with signals that would initiate inflammation - the abnormal inflammatory respond has been prevented. This is encouraging and suggests that vitamin D might be a good supplement to the diet of  CF sufferers to prevent them developing ABPA, though as this is a conclusion based on a single laboratory experiment rather than on real people we cannot be sure.

Needless to say supplementation of the diet of ABPA patients would be a very cheap and thus eminently do-able, especially as vitamin D has few notable side effects when taken in moderation. Success cannot be guaranteed however as it is very simplistic to suggest that all ABPA sufferers (CF and non-CF) have low vitamin D levels in their blood and to assume that the reason for that is dietary deficiency, but it might be worth patients self-checking their diets for foods rich in vitamin D.
Foods rich in vitamin D are oily fish, liver, cod liver oil and dairy products and of course sunshine is an important source.

Thursday, 12 August 2010

Aflatoxins claim victims in Africa

Recent reports from Africa tell of a major outbreak of aflatoxin poisoning in Kenya which has already resulted in one death, a small child.
Aflatoxin is produced by a wide variety of Aspergillus species and is highly toxic to people & animals when eaten in contaminated food.

In this case the contaminated food is known to be maize that is grown and then stored without sufficient drying or is stored in damp conditions. Maize is the main staple food in many parts of Africa and is grown for food and for profit. It is interesting to note that this has happened in this case at the end of a period of drought and famine as  we  know that Aspergillus is good at infecting a crop that is stressed by damage or water shortage so perhaps that is a factor in this outbreak?

This is the latest in a series of outbreaks of aflatoxin contamination. The largest recorded recent outbreak was in 2004 which led to 317 cases of aflatoxicosis and 125 deaths. Apart from the cost in human lives there is a huge cost to the livelihood of many farmers across a large area - the report mentions 29 districts affected. Contaminated grain cannot be sold for a good price or cannot be sold at all (depending on the level of contamination) and millions of bags of grain have been affected.

We have written several times of the methods being developed to limit aflatoxin contamination of crops:

New biopesticide Aflasafe™ may solve Kenya's ongoing maize contamination problem.

New biocontrol agent for Aspergillus contamination of peanuts

but clearly there are some more immediate basic solutions that can be tried first. Education of farmers about how to avoid creating conditions condusive to mycotoxin production is one mentioned in the report, and the Kenyan government is looking at providing drying machines to dry grain properly in the area affected to try to avoid future problems.

For the maximum allowable limits of mycotoxins in Africa: see
For a lot more information on worldwide mycotoxin foodstuff regulations see

Monday, 2 August 2010

Major Breakthrough in Understanding of Disease-Causing Fungi.

Scientists at the Departments of Biology and Chemistry, National University of Ireland Maynooth (NUI Maynooth), led by Professor Sean Doyle, in collaboration with Austrian collaborators, have made a major breakthrough in the area of the molecular microbiology of pathogenic fungi.

They have discovered how a pathogenic fungus protects itself against one of the toxins it can produce to reduce our immune response and so cause infection. The fungus in question is called Aspergillus fumgatus, which can cause severe disease and death in organ transplant patients.

The findings have just been published in the prestigious journal, PLOS Pathogens.

Doyle explained, “The fungus, Aspergillus fumigatus, is the major opportunistic pathogen of immunocompromised individuals, including bone marrow and solid organ transplant patients. We wondered why the organism could produce a molecule, called gliotoxin, which both kills cells and disrupts our immune response, yet had no effect the fungus itself? We found that a single gene called gli-T is present in Aspergillus fumigatus and ultimately acts to ‘inactivate’ gliotoxin. What really surprised us was that although gli-T is just one gene in a cluster of 13, all of which had been thought only to make gliotoxin, it can operate independently of all other genes in the cluster to protect the fungus against gliotoxin. This is quite an unusual phenomenon in fungi, explains a number of recent observations by others working in this research area, and has significant biotechnological potential.”

The work started almost four years ago, as a small component of an inter-institutional PRTLI programme with DCU (Professor Martin Clynes), and an EU programme at Maynooth co-ordinated by Dr Shirley O’Dea. It has involved significant inter-disciplinary and cutting-edge research at the interface of molecular biology and chemistry. For instance, the techniques used to reliably study gene function in Aspergillus fumigatus have only become available in the past few years and Maynooth is one of a small number of laboratories, along with that of collaborator Professor Hubertus Haas (Innsbruck, Austria), where this technology is used. In addition, the work involved the study of proteins of fungal origin, so-called ‘fungal proteomics’.

Maynooth has won competitive funding for the high-throughput instrumentation required for proteomic studies and has significant expertise in this area, not just for the study of human pathogens like Aspergillus fumigatus, but also to investigate plant pathogenic fungi like Armillaria mellea.

As for the future, the researchers intend to commercialise aspects of their findings and a European patent application has been filed on the technology, which has significant potential to improve the quality and yield of diagnostic and therapeutic proteins produced by fungi.


Image 1: Aspergillus fumigatus growing on petri dishes. It can be clearly seen that once the protective gene has been removed from the fungus that it can no longer grow in the presence of one of its own toxins (gliotoxin). This tells us that this gene is responsible ‘self-protection’ against gliotoxin.

Image 2: Microscopic image of Aspergillus fumigatus. It is a filamentous fungus and so grows in a strand-like manner. Panel A shows a green-tagged form of Gli-T. When the toxin (gliotoxin) is added it can be seen in panel B that more tagged Gli-T is produced to protect against the toxin.

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