Public Funding for Agroceutical Products Ltd

As we age there is reduction in the effectiveness with which our gastrointestinal tract functions, which has the consequence of reducing the absorption of nutrients from our diet. This is one of the contributors to the malnutrition suffered by many older individuals. Interestingly the changes to gastrointestinal tract functioning also leads to increased inflammation throughout our bodies as well as increased inflammation in our brains. This age-related increase in inflammation has been termed "inflammaging", and contributes to the age-related diseases and conditions that have a common feature of increased \[dysregulated\] inflammation, including type 2 diabetes, cardiovascular disease, joint disease and cognitive decline. Therefore, the gut-brain axis plays an important role in age related cognition decline. The reduced function of the gastrointestinal tract also alters drug absorption, and decreases protection against ingested pathogens \[microbial, fungal, and viral\]. The latter point is significant because the gastrointestinal tract provides the largest surface area of contact between us and our environment. The research team has the combined expertise required to address the consequences of reduced gastrointestinal tract function in ageing. The three Companies involved, Agroceutical Products Ltd (Wales), Neurodyn Life Sciences Inc (Canada), and PostBiotics Inc. (USA), have used a common approach to exploit natural product-based strategies to maintain and extend the human health-span. They will collaborate with Aberystwyth University's Departments of Life Sciences and Psychology. This academic team are experienced in working on translational Research and Development with the Food, Drink and supplement industry partners. Neurodyn Life Sciences Inc., has developed a natural product-based formulation called Cerbella, that is composed of a proprietary blend of specific components of ginseng, green tea, and essential fatty acids \[Omega-3's\]. This formulation has been demonstrated clinically to improve the efficiency of brain function in healthy elderly people. Postbiotics Inc., has developed a dietary supplement POZIBIO, based on a component of bacterial cell walls that improves gastrointestinal tract function by restoring the protective mucus layer that coats the intestine lining facing the ingested food that is being digested and absorbed. We will determine if the improved function of the _Gut & Brain_ following intervention with both POZIBIO and/or Cerbella leads to an overall health benefit when compared with placebo control. We intend to examine changes in cognition and blood inflammation indicators, in an older people cohort who receive POZIBIO and Cerbella in their diet.

This is a 48-month feasibility research project which aims to develop tools which will contribute to the COP26 Global Methane Pledge of cutting global methane emissions by at least 30% by 2030\. The project will seek to develop a naturally sourced nutritional additive to reduce methane emissions from ruminants, which currently account for 80% of the total methane emissions from agriculture in the UK. The project will also address the requirement to improve the efficiency of feed utilisation by ruminants, which will reduce the demand for imported high-protein feed materials, supporting sustainable milk and meat production. The rural economy will also benefit through diversification and employment opportunities for farming, an industry currently challenged by post-Brexit pressures. The project is based on greater use of locally available plant-based compounds called alkaloids, which can be extracted from daffodils. As daffodils are grown widely throughout the UK, production and extraction these compounds can be local, sustainable and resilient. Preliminary data estimates that by using a specific alkaloid from daffodils, direct methane emissions from ruminants can be significantly reduced whilst simultaneously improving the efficiency of feed protein utilisation by 50%. Improving feed protein utilisation will lead to increased productivity of the ruminant sector whilst reducing the production of nitrous oxide, another potent greenhouse gas. This would subsequently reduce the requirement for high-protein imported feeds such as soyabean meal, improving the sustainability of British farming. This project presents several benefits to both UK agriculture and wider society. \*Reduce the carbon footprint of the ruminant livestock sector by developing and validating a novel technology geared to boost feed protein efficiency whilst reducing methane emissions (currently more than 90% of the corporate dairy industry emissions are methane produced by cows). \*Improve productivity and resilience in the dairy sector by reducing the need to feed high-cost imported feed materials. \*Establish a UK-based supply chain to support the diversification of UK agriculture and boost the rural economy by providing higher incomes for farmers. \*Improve food security in the UK and provide rural job opportunities.

**NextGenGelCap** is aimed at developing a strong supply chain to support the local production and subsequent export of UK-produced nutraceuticals to the US-Canadian market. At the heart of the program is the development of a new encapsulation technique that will increase drastically the shelf-life of oxygen sensitive nutraceutical formulations, involving new high oxygen barrier edible membrane, and an encapsulation process under nitrogen-blanket. **NextGenGelCap** is led by Agroceutical.

**DAFOMI** is a 5 months feasibility research programme to develop emerging solutions to secure post COVID recovery and sustainable increases in the production of milk and dairy products providing diversification opportunities for farming and employment challenged by COVID-19 and Brexit pressures. **DAFOMI** will directly address the disruption of the wider UK dairy supply chain by providing technologies to improve current protein-feed efficiency, using subproducts of the agricultural industry rich in alkaloids, and enabling future market-growth in speciality dairy products (cheese and others). **DAFOMI** will benefit farmers who rely on ruminants for their livelihoods by providing higher incomes, more plentiful, nutritious, and cheaper food, and by generating patterns of development that provide employment and benefit to rural areas while at the same time impacting positively on the reduction of greenhouse gas emissions. **DAFOMI** will obtain trial data validating a disruptive technology geared to boost dairy feed protein efficiency. This will reduce the carbon footprint of the sector, by reducing direct greenhouse gas emissions (currently more than 90% of the corporate dairy industry emissions are methane produced by the cows, mostly in the form of methane). **DAFOMI** approach is based on greater use of locally available **alkaloids** very specific plant-based chemicals, to improve feed and animal nutrition. **DAFOMI** targets matching ruminant production to adequate feed preparation to maximize protein feed efficiency and improve milk protein content. **DAFOMI** will improve the country's food security and provide the potential for rural job security and further employment for those losing jobs in other sectors. Preliminary **DAFOMI** data estimate that we could improve feed efficiency evaluations by 5-20%, while simultaneously reducing direct methane emissions by 30-35+%.

Awaiting Public Project Summary

To develop and document a set of records and standard operating procedures to enable galanthamine produced from daffodils to meet the regulatory requirements of the Medicines and Healthcare Regulatory Agency and the Food and Drug Administration.

Galantamine is a pharmaceutical product that had been an approved Alzheimer’s Disease treatment since 1998. Galantamine can be synthesised chemically but it is a difficult and expensive process. Producing galantamine from galanthamine extracted from plants is more cost effective, but supplies are limited. Daffodils are an economically feasible plant source for cultivation in the UK, and growing daffodils in upland areas triggers a 50% higher yield of galanthamine. This proposal will deliver a new approach for producing galanthamine based on integrating daffodil growing into existing upland pasture. This will increase the economic sustainability of hill farming by providing farmers with a high value crop while maintaining traditional farming systems in the upland areas. The project will develop the required machinery, quantify the yield of galanthamine achievable, and assess the impact on sheep performance of incorporating daffodil production into grazed pastures.

This short feasibility project aim at improving the industrial process of extraction of Galanthamine, a Daffodil derived alkaloid, presently used for the treatment of moderate Alzheimer’s, the production of anti-nicotine patches, and hair growth stimulants for the cosmetic industry. Galanthamine is one of the few medical drugs that is approved by NICE to treat Alzheimer's, a disease that affects 35 millions of people worldwide. This will support broader activities aimed at developing an UK-based supply chain aimed at producing and selling the pharmaceutical.

Protozoal organisms in the rumen of animals such as cattle and sheep reduce their ability to utilise protein efficiently and increase their production of methane, an important greenhouse gas which may lead to increased global warming. Saponins from ivy have been shown by the team to reduce protozoal growth but the effect wears off as the protozoa remove sugars from the saponins and inactivate them. Glycosidase inhibitors from some food waste materials can slow this inactivation. The team will find the best combinations of saponins and glycosidase inhibitors for commercial production. Other uses are also also being considered by the project partners.