Folium Science using Guided Biotics® to reduce Campylobacter in farming systems for sustainable agriculture

Dr Karima Djacem – FOLIUM Science

FOLIUM Science has recently been awarded a grant through Department for Environment, Food and Rural Affairs Farming Innovation Programme (FIP), delivered by Innovate UK. This will allow FOLIUM Science to continue to showcase the utility of our Guided Biotics® technology to sustainably address major challenges within farming practices and to boost environmental resilience. The award allows us to continue to build our excellent relationship with the University of Bristol.

Modern agriculture’s challenge lies in increasing productivity whilst ensuring environmental sustainability. Animal production is making significant strides towards reducing the use of antibiotics driven by the rise of Antimicrobial Resistance (AMR), especially zoonotic pathogens that compromise human health. As a consequence of reducing the use of antibiotics, endemic diseases are re-emerging as major zoonotic problems, such as Campylobacter.

Campylobacter represents a major One Health challenge and zoonotic disease. Poultry production is considered the primary source. The industry aims to have less than 4 x log10 Campylobacter per gram of caecal content in broilers (poultry for meat) at point of slaughter, but blooms of Campylobacter often reach 9 x log10 or more particularly late in the production cycle and on transfer to the slaughterhouse.

Currently the only effective controls are biosecurity measures and abattoir management that do not tackle the problem at its source. Despite improved biosecurity measures, Campylobacter remains a significant risk to human health. Vaccines have been developed without real success in controlling the pathogen. Feed acidification and nutritional supplements including probiotics, prebiotics and organic extracts have met with limited success. Therefore, control measures for Campylobacter are needed urgently in poultry production. However, to secure the future of farming and reinforce resilience in agricultural systems, innovative approaches to pathogen control are necessary.

FOLIUM Science will be the first biotechnology business to commercialise CRISPR/Cas-based solutions for the feed & food industries for precise bacterial control. We aim to address the Campylobacter challenge by leveraging our patented Guided Biotics® technology platform, which has already seen impressive efficacy with its first product, BiomElix® One, in controlling Salmonella enterica in poultry. The focus of this project will be the development of a pre-commercial CRISPR-Cas validated system for the control of Campylobacter in poultry production.

This 36-month industrial research project aims to advance the existing proof of concept through in vitro, ex vivo, and in vivo testing to select a product candidate that will be ready for development, manufacturing, and commercialization upon successful completion. Through our well-established and strong collaboration with Tristan Cogan, Senior Lecturer in Infectious Disease at the Bristol Veterinary School, FOLIUM Science seeks to de-risk its Guided Biotics® technology for Campylobacter and demonstrate the efficacy of this innovative solution in poultry, leveraging their expertise in Campylobacter jejuni trials.


FOLIUM Science launches rapid lateral flow test for the detection of Salmonella.

New molecular test uses Guided Biotics® technology.

FOLIUM Science will be taking to the stage at the AgriTechE REAP Conference on November 8th to launch the latest of their innovative product range to improve animal health and productivity.

The new product, called SWIFTR, is a lateral flow test for the detection of bacterial infection. The first product in the range will be launched at REAP and is for the rapid detection of Salmonella in poultry production. The time it takes to get the test result and identify an infection is reduced to one hour compared to currently available tests which can take up to five days.

The test is also simple to use and requires no special training or laboratory equipment so that it can be carried out on the farm or where action can quickly be taken to protect the health of the flock and to prevent the spread of infection.

Because SWIFTR is a molecular test that uses advanced molecular biology, it can identify small pieces of genetic material from the pathogenic bacteria that the user is looking for in the sample, even down to individual Salmonella serovars where necessary. This means that the test is extremely accurate.

The extent of the infection can also be quantified so that the appropriate measures can be put in place.

“We know that rapid testing for bacterial infection is the Holy Grail for the food industry” say FOLIUM Science CEO Ed Fuchs “Our first SWIFTR test is for the detection of Salmonella but we are also developing tests for other bacteria such as Enterococcus, Clostridium and E.coli. And whilst poultry production is the first step on the ladder, there are numerous applications in animal farming and across the food industry for a test that is quick, simple, and accurate. We are working with our partners in the poultry industry to roll out the use of SWIFTR in poultry production in early 2024.”

SWIFTR uses the same Guided Biotics® technology that has been developed for FOLIUM Science’s feed additive BiomElix. Next year sees the launch of the first product in Brazil, BiomElix One, a feed additive for poultry that targets all Salmonella serotypes.

FOLIUM Science’s Guided Biotics® are based on CRISPR-Cas technology and have received endorsement from the Brazilian National BioSafety Committee (CTNBio) as a non-GM ‘new-breeding technique’. CRISPR-Cas is a defence system that has evolved in bacteria to protect them against invading viruses. FOLIUM Science is harnessing this natural system to manage and modulate bacteria in the microbiome.

“The launch of SWIFTR perfectly complements our feed additive portfolio” says Ed “Not only can we offer a product that detects the presence of infection, but we use the same proprietary Guided Biotics® technology to create and produce an additive that modulates the microbiome to help control infection in the digestive tract of the animal.”

FOLIUM Science will be attending AgriTechE REAP conference in Cambridge, UK on November 8th. The team will be demonstrating the SWIFTR product at their exhibition stand.


Embracing Innovation in BioScience

In the second of our series of articles, FOLIUM Science considers some of the big challenges in the food supply chain, how attitudes to bioscience and new technologies differ across the world, how funding of new research needs to be managed and where the investment opportunities in bioscience will be.

We asked FOLIUM Science’s in-house experts to reflect on the role that bioscience plays in the food supply chain and draw on their own personal experiences to consider how the future might look.

FOLIUM Science Chief Development Officer, Dr Simon Warner shares some thoughts on how technological change is adopted.

“The last ten years has seen a very different response to new technology depending on where you are in the world.  The US, China and Brazil have embraced new technology much faster than Europe. The focus in Europe has been more orientated towards biological solutions and pesticide reduction, for example, neither of which are bad options but some of the new potent technologies have not fared so well as a result.”

This could be due to inherent beliefs and behaviours that are ingrained within respective societies, as well as the different rates of agricultural and economic growth across the different regions. But it will also be a function of the perceived future and the skills that the next generation will require.

Simon believes that education in the sciences may well be one of the driving factors that impacts the level of adoption of new technologies.

“Developing countries are trying really hard to ensure the next generation benefits from as good a scientific education as possible, whereas in Europe we value other things. The UK in particular is more focussed on finance and other services, and core agriculture in Europe is very small with only a few farmers per head of population. This means that many European consumers have lost touch with agriculture so, although we have seen some great new technologies being developed, their deployment and public acceptance is different around the world”

Genetically modified organisms (GMOs) are an example of this. First developed in the 1970s and developed through second generation technology in subsequent decades, today’s synthetic biology techniques are taking it through a third evolution with the advent of CRISPR technology.

This type of bioscience has the ability to quicken the pace of agricultural growth. The modern strains of wheat and barley were developed using selective breeding of the desired genetic traits; synthetic biology, such as CRISPR can play an important role in this process.

In previous roles, Simon’s experience has been with viral diseases such as Malaria, Zika and Dengue fever.

“Malaria still kills up to three million people a year, with children disproportionately affected. These diseases are mosquito-based and as yet there has been no vaccine developed that is really effective, so the only current route is to manage the insect population”

Simon believes that lessons can be learnt from the way in which these projects were funded. Much of the work on mosquito borne diseases was funded by the Bill and Melinda Gates Foundation, but the Covid-19 pandemic poses a question about whether we will see greater collaboration between scientists or a more siloed, competitive approach.

“Innovate UK has announced a £20m Covid-19-related competition for UK businesses with maximum grants of £50,000 per business. This encourages competition but not collaboration. It is therefore up for debate whether many small laboratories with small amounts of money will deliver a better solution than a bigger collaborative consortium with say a minimum of £1m. Different countries will take different approaches, but it would be good to see the scientific community working together on this challenge”

When it comes to protecting consumers from ongoing food safety risks, it is a matter of making sure that the public do not take food safety for granted and realise that without good science, this will become even more of an issue.

“We could say that banning the use of antibiotics as a growth promoter for livestock production is a sensible policy and to reserve the  use of antibiotics only as veterinary medicines, but the consequences of this could also inadvertently cause contamination in the food supply chain with pathogens and unwanted bacteria such as Salmonella. Therefore by reducing the use of antibiotics to address the issue of antimicrobial resistance, other risks can occur. So we need alternatives that will support animal wellbeing and reduce the risk of infection. Our Guided Biotics® platform is designed to address this”

(Download our technical guide to find out more

Simon is clear that science will play a big part in a sustainable and secure food supply. With an ever-growing world population, there are some big risks and challenges ahead.

“We all forget, as complacent Europeans, that the world will not have enough food by 2030, so there is a big risk staring us in the face. There won’t be enough food or enough animal protein. This is because of productivity gaps and behavioural changes. China is demanding more meat and the consumption of meat in the western world will not be sustainable as crop acreage and water supply become limiting factors. Science has a role to play in supporting increased productivity from the existing agricultural acreage to combat the issues caused by climate change, changes in rainfall patterns and water scarcity”.

Biotechnology has solved issues of food preservation before.  The use of fermented foods and drinks to combat dirty food and water by developing beers and breads is an example of how biotechnology has always played a role in the safety of our food.

So, in the long term what does this all mean for investors and where should they look to support biotechnology in the future? Simon is clear that technology to drive productivity and efficiency will be key.

“In the long term, the problems that face us will be how to increase crop yield in a world where fewer new crop protection products  are being registered . Finding ways to protect plants and crops is therefore becoming more challenging. The opportunities lie in technology that can enhance productivity and efficiency in a world where resources are becoming increasingly stretched. And, in recognition of the differing public attitudes towards new technology, biological solutions can only improve the rate at which it will be adopted”.

To conclude, new biotechnologies for the food supply chain are vital but the rate of adoption will depend in part on how local populations perceive the science. Implementation is more likely in countries that have historically been more receptive to new technology such as the US, Asia and South America or where a science-based decision-making process is regarded as important.

The optimisation of funding models for research and development will play a part in the success of new initiatives, including finding treatments for global pandemics. It remains to be seen whether a competition-driven or collaboration within larger consortia approaches are more effective.

Finally, the opportunities for investment in biotechnology will be in technologies that deliver production efficiencies, higher yields and that can protect public health from unwanted pathogens.


BioScience Keeps Us Safe

Never has there been a greater focus on the role of science in keeping us all safe and how the understanding of bioscience and genetics can deliver breakthroughs that can transform our future. Not just in protecting our health from the threats of viral pandemics and antimicrobial resistance (AMR) but across the food supply chain. More than ever, the food industry is reliant on good science; for example to support productivity, to protect animal and human health from disease, to improve crop yields and ultimately to deliver enough safe food to feed an increasingly hungry world.

In this series of articles, FOLIUM Science’s in-house experts reflect on the role that bioscience plays in the food supply chain and draw on their own personal experiences to consider how the future might look.

FOLIUM Science’s Chief Technical Officer, Dr Hadden Graham shares his thoughts on some of the bigger breakthroughs in bioscience.

“Biotechnology has been important for thousands of years. Even as far back as Egyptian times when fermentation was used to preserve food. Selective plant breeding has been carried out for centuries, but the big breakthroughs came when there was a greater understanding of how to speed up the process and how to deliver predictable outcomes based on an understanding of the genetic make-up of an organism”

Genetics sits at the core of much of the science that is applicable in the food supply chain. The improvement in breeding stock amongst poultry producers is a good example

“These breeders aren’t using GM to improve their stock. They are selecting based on performance and using big data to identify and produce the desired genetic traits in the next generation. And it’s not just about performance. Genetic selection will support better animal health and welfare by selecting for leg strength or bone strength for example. We now understand so much more about animal genetics, but we still need to learn more about how to feed the genetics to help control the diseases”

But delivering the breakthrough bioscience and innovation to market has its challenges. Particularly, in Hadden’s view when it comes to consumers.

“Some people think it is the regulatory authorities that present the greatest barrier to bioscience innovation, but a bigger problem can be the way that consumers perceive it. Consumers often fear the unknown and, on the whole, don’t understand science. This isn’t necessarily their fault as science is getting pretty complex and not as easy to understand as it might have been 20 years ago but the degree of consumer resistance to some aspects of bioscience has limited some applications, even though the regulatory authorities have the appropriate systems and processes in place”

With scientific experts in the headlines every day, one outcome of the corona virus pandemic could be a greater trust in science amongst consumers alongside a more intense focus on where our food comes from.

“Governments across the world are now realising the importance of listening to experts. They need the scientists to tell them what to do as there is no other way to deal with the problems we have to face in the world today. This applies to the long-term provision of our food as well as to the combatting of diseases. For consumers, the key question will be around trust. Will science regain the trust of consumers that has eroded in recent years?. At the very least we should expect a shift in attitudes towards those with genuine expertise and experience. It’s an important time for the biotechnology industry; we are on the cusp of finding solutions to some of today’s big health issues including many cancers and diseases. Our CRISPR based Guided Biotics® technology is a part of this”

(Download our technical guide to find out more

Hadden’s first-hand experience in delivering breakthrough bioscience to market for the food supply chain was demonstrated in the late 1980’s when feed enzymes were first launched by the pioneering feed additive producer, Finnfeeds. Although enzymes had unwittingly been used for centuries in beer and cheese production and had been studied in animal performance trials as far back as the 1920’s it wasn’t until the right market opportunity presented itself that this billion-dollar industry was born.

“ Although the actions of enzymes in animal feeds was understood, the catalyst and commercial breakthrough was the impact that feeding enzymes had on barley fed poultry. Domestically grown barley was significantly cheaper than imported wheat but had historically created problems with litter when fed to birds. The addition of enzymes into the feed transformed this and the rest, as they say is history. This was an example of where good science reacted to the market opportunity and was rapidly developed by commercially astute scientists into a commercial application“

So what lessons can we learn from these reflections?

Firstly, although bioscience has played a role in the production of safe food for centuries, the importance of delivering science-based solutions for the food supply chain has never been greater. Population growth and changing consumer consumption patterns means that efficiency of production will rely on a deep understanding of the drivers of greater productivity. And beyond these ongoing pressures, the current threats to human health posed by AMR or viral pandemics are very real and can only be solved by a commitment to invest in the research and innovation required.

Secondly, we should expect to see science as the hero in our future stories and a return of a world where science trumps politics. Or at least that’s what we should hope for.

And finally, there are enormous commercial opportunities for investors in biotechnology and for science driven organisations that can not only develop products that improve the productivity of food producers and support the production of safe food but that can put the commercial operations in place to move swiftly to market.


FOLIUM Science at APSS 2020

FOLIUM Science CTO, Dr Hadden Graham attended APSS 2020 to present a paper on “Selective removal of Salmonella from broilers using a novel technology


TRISTAN COGAN, HOLGER KNEUPER, HADDEN GRAHAM and MARTIN WOODWARD present a trial for a new CRISPR-based patented technology introduced into a vector Escherichia coli probiotic designed to selectively remove all Salmonella serovars from the bird gut.


    Over the past few decades the meat, egg and milk sectors have faced the need to reduce the routine use of antibiotics in animal production, and the high incidence of food poisoning associated with animal product consumption. Approximately 130,000 tonnes of antibiotics were used in 2013 worldwide, with 75% of this in animals. Up to 90% of these antibiotics can be excreted into the environment via urine and feces, and approximately 400 resistance markers against 25 antibiotics can be found in chick caecal bacteria. Globally, around 700,000 human deaths per annum are attributed to antibiotic resistance and this is predicted by the FAO to increase to 10 million by 2050. With rising concern about the development of antibiotic resistance in human health, regulators, consumers and retailers have led the drive to reduce the sub-therapeutic use of antibiotics in animal feeds to zero. Endemic disease is re-emerging, adding costs to animal production systems and driving the need for alternative non-antibiotic interventions.

Food poisoning continues to be a problem across the world, with salmonellosis cases now increasing in many countries. Non-typhoidal salmonellosis is reported to cause over one million infections, 19,000 hospitalizations and over 400 deaths annually in the US, with some Salmonella serovars in food showing antibiotic resistance. Although salmonellosis incidents are traditionally relatively low in Australia, recent egg-associated outbreaks have brought this back to the attention of the regulators and consumers.

It is now possible to cause a targeted bacterium to self-destruct through the use of CRISPR, the biological sequences that make up the bacterial immune system. This technology is extremely precise, such that it can target a specific bacterium or a defined range of bacteria. This means that, unlike many antibiotics, it can be used to remove only the unwanted bacteria in the animal gut microbiome and leave beneficial gut flora unchanged, potentially enhancing the well-being of the animal. One way to induce bacteria in the animal gut to self-destruct is to introduce a suitable plasmid into the target organism(s) through conjugation via a probiotic included in the feed or drinking water. The current trial looks at the ability of this technology, named Guided Biotics, to reduce Salmonella colonization in challenged broilers.


A non-pathogenic Escherichia coli strain was used as the vector in this trial, and was loaded with a plasmid including a CAS sequence and 3 target sequences specific to all Salmonella serovars (Guided Biotics). Ross 308 as-hatched birds (165) were obtained on day of hatch and housed under controlled biosecure conditions, with access to water and standard commercial rations ad libitum.Birds were dosed continually from day 1 with either:

  1. No addition to water (45 birds)
  2. Unmodified E. coli vector at 108 cfu/mL drinking water (45 birds)
  3. Anti-Salmonella Guided Bioticsat 108 cfu/mL drinking water (45 birds)

In parallel, a group of 30 birds was dosed orally with 0.5 ml 105 CFU/mL Salmonella Enteritidis strain FS26 on day 1. Birds were checked for Salmonella colonization at day 3 by cloacal swab (ISO 6579-1:2017). On day 5, three verified Salmonella-colonized birds (seeder birds, with >105 CFU/g in swabs) were marked and added to each of the test groups.

Fifteen non-seeder birds from each group were euthanazed on day 12 (7 days post-mixing with seeder birds) and caecal contents were counted for Salmonella using both direct and enhanced methods. Caecal samples were serially diluted in PBS before plating onto XLD agar for direct counts, whilst for enhanced counts the samples were first incubated in Selenite Cystine broth for 18 hrs at 41oC before plating and counting (ISO 6579-1:2017). For the purpose of data transformation, samples negative in either method were allocated a count of 1 CFU/g, while those negative in direct counts but positive in the enhanced method were allocated 500 CFU/g. Body weights of the remaining birds were monitored at day 42. Counts and weights were log transformed and statistical analysis conducted using GraphPad Prism. Data were assessed for normality of distribution using a D’Agostino and Pearson omnibus normality test and non-normal were analysed using a Kruskall-Wallis test with Dunn’s multiple comparison test post hoc. Differences were analyzed using Fisher’s exact test.


All birds in the seeder group showed cloacal Salmonella counts of >105 CFU/g by day 3. By day 12 (7 days post introduction of seeder birds to test groups) all birds in the Control and E. coli vector-only groups were positive using the enhanced counts method, exhibiting caecal counts of 500-4,000,000 CFU/g (Table 1). Twenty two of these 30 birds were also positive with direct counts. However, when the anti-Salmonella Guided Biotics was added to the drinking water, Salmonella was not detected in any birds with the direct method, and only 8 of the 15 birds tested were positive with enhanced counts. The Guided Bioticstreatment reduced (p < 0.001) mean Salmonella counts by approximately log-3 (from log 4.12 to log 1.26, equivalent to 14,200 CFU/g to 18 CFU/g) and also improved 42-day liveweight by 15% (p = 0.02; Figure 1).

Table 1: Influence of the E. coli vector alone or Guided Biotics with an anti-Salmonella plasmid on caecal Salmonella counts (log10 CFU/g, enhanced counts method) in 12-day old Salmonella-challenged broilers.

  Control E. coli vector only Guided Biotics
Mean Salmonella count (log10 CFU/g) 4.12a 4.74a 1.26b
Median Salmonella count (log10 CFU/g) 3.30 4.95 ND
Maximum Salmonella count (log10 CFU/g) 6.60 6.60 2.70
Minimum Salmonella counts (log10 CFU/g) 2.70 2.70 ND

Figure 1: Influence of Guided Biotics on bird liveweight at 42 days of age.


The challenge method employed in this study is consistent with that often use in Salmonella vaccine tests and may be regarded as severe. All seeder birds were infected when introduced into the test pens, and the Salmonella shed to in-contact birds would be expected to be highly infective. This was confirmed by the universally high caecal counts in all Control birds 7 days after seeded-bird introduction. Conversely, the Guided Biotics, delivered by conjugation in the digestive tract, was able to stop Salmonella colonization in 8 out of 15 (53%) of the test birds. The average Salmonella count in caecal digesta was also reduced by approximately log3 (thousand-fold) and the maximum Salmonella count lowered from 4 million CFU/g in Control birds to 500 CFU/g in Guided Biotics treated. The 15% increase in liveweight of birds fed the Guided Biotics relative to the Control birds further indicates the severity of the Salmonella challenge employed in this trial. The lack of any effect of the E. coli vector on colonization confirms that the Guided Biotics plasmid was essential for Salmonella reduction.

This initial trial establishes the capability of Guided Biotics technology to specifically remove unwanted bacteria, in this case a single Salmonella serovar. The tested Guided Biotics is designed to target all known 2,400 Salmonella serovars, and laboratory trials have established efficacy across the main serovars involved in human food poisoning. Ongoing laboratory tests have also indicated that solutions for other unwanted bacteria, such as Clostridium perfringens and Avian Pathogenic E. coli, are feasible. Furthermore, because the design of the targeting is specific, tests have confirmed that off-target killing of desirable or commensal bacteria can be avoided.


It is clear that this Guided Biotics technology has the potential to make a substantial contribution to the replacement of antibiotics in poultry production, reduce zoonosis incidents and maintain bird performance in antibiotic-free diets.

*Tristian Cogan ( is with the Veterinary School, University of Bristol, UK. Holger Kneuper (, Hadden Graham ( and Martin Woodward ( are all with Folium Science. References are available on request to Hadden Graham. This paper was presented at the 2020 Australian Poultry Science Symposium.