Sub-acute ruminal acidosis: an interdisciplinary approach to understand and prevent a multifactorial disease

Ruminant animals, including cattle, sheep and goats, rely on microbial activity in their digestive tract to digest grass and other forages that they consume. A balanced, stable digestion (fermentation) is essential for good growth or milk production. Most livestock producers require productivity higher than that which can be sustained by forage feeding alone, and include some grain in the diet to increase production rates. Gut microbes produce acids more rapidly from the starch in grain than the cellulose in forages, leading to lower pH values prevailing in grain-fed animals. This has adverse effects on the microbes, which require near-neutral pH to perform optimally. This sub-acute ruminal acidosis (SARA) is a major economic and health issue in ruminant livestock production. Animals suffering SARA are less productive, and they suffer from necrosis of the rumen wall, liver abscesses and laminitis. SARA is often difficult for the farmer to detect - it is 'sub-acute' and can only be detected easily at slaughter. SARA is an under-researched condition, such that only a small number of papers have addressed the dietary and microbiological causes of SARA and its underlying pathology, particularly concerning the role of the large intestine.
This project aims to understand why SARA is prevalent on some farms but not others, an observation that is common knowledge but not well documented. Farm management conditions and nutrition will be monitored in these farms, and the animals will be followed to slaughter, when the extent of pathological damage will be assessed. Samples of ruminal digesta and wall tissue will be taken for analysis and tissue necrosis, abscesses and laminitis will be scored. SARA also affects some animals but not others within a herd. Remote motion-sensing technology will be used to externally monitor movements, such as rumination activity, that may alert livestock producers to problematic animals. Post mortem analysis will also be carried out on these animals.
The root cause of SARA lies in altered gut microbiology. Digesta samples will be taken forward to describe the microbes that are present in the rumen and intestine in susceptible and non-susceptible animals, with the idea that some microbial species may be particularly important in causing the disease while others may be protective. Candidate 'probiotic' bacteria isolated from non-susceptible animals will be investigated with a view to developing them as feed additives. The role of soluble lipopolysaccharide (LPS) in the inflammation will be investigated. LPS is released when bacteria lyse - it is known as 'endotoxin' in human medicine. Materials that may bind soluble LPS to prevent inflammation will also be investigated as potential feed additives.
The overall aims are to explain the underlying mechanism of pathogenesis of SARA, to investigate if microbiome analysis can predict the severity of SARA, and to develop simple, non-invasive methods for monitoring animal behaviour relating to SARA and preventing the condition. Three academic partners, three complementary companies, Quality Meat Scotland and DairyCo are involved in the project. The industrial partners will ensure that relevance to the livestock industry is maintained throughout the project and that the pathway to impact will be short and rapid.

Sub-acute ruminal acidosis (SARA) affects some cattle herds, but not others, and individual animals within herds, but not others. The root cause of the dysfunction is the loss of control of ruminal and possibly intestinal pH. SARA is generally caused by grain feeding, but the basis of the variability requires better definition and the precise cause of inflammation and pathology remains uncertain. This project will monitor six beef and two dairy herds for nutrition and management and relate the information to post-mortem scores of ruminal wall lesions, liver abscesses and laminitis. The potential value of remote motion sensors in alerting farmers to problematic animals will be explored. Ruminal digesta and ruminal epithelial tissue samples taken post mortem will be analyzed by state-of-the-art microbiomic analysis based on 16S rRNA gene sequences, in order to identify significant differences in microbial communities in different animal types. Different Escherichia coli biotypes will be monitored. Bacteria will be isolated from least affected animals for their ability to inhibit the growth or adhesion properties of E. coli, on the basis that these animals may already possess bacteria that protect them from SARA. Candidate strains will be evaluated for their potential usefulness as probiotics to prevent or treat SARA. The hypothesis that soluble lipopolysaccharide (LPS) lies at the heart of the inflammation which results in pathology will be tested by measuring the quantities and nature of cell-free LPS in different animals. Possible feed additives that adsorb or break down LPS will be evaluated in digesta samples from badly affected animals. Demonstration animal trials will be carried out in the third year of the project to test the potential nutritional, management and feed-additive solutions identified by the project's results.

Who will benefit from this research and how?
A wide international spectrum of academic researchers will benefit from the project, because SARA is a widespread problem internationally. Researchers interested in ruminant health and welfare and those whose main interest is ruminant gut microbiology will be the primary beneficiaries. They will be able to translate the results to their own production conditions where SARA is endemic. The results will be of wider interest, however, because although SARA is a disorder that afflicts ruminant species, researchers interested more generally in inflammation that originates in the gastrointestinal tract of other species, including man, will benefit. Related fields include equine health and poultry production: researchers in these areas will build upon the novelty of this project to determine if the aetiology of their target diseases, in terms of microbiology, inflammatory factors and pathology compare. New research and research proposals for these different animal species could result. Medical researchers may benefit too: the concept of soluble LPS has not yet been explored in human disease, for example. One might speculate that soluble LPS may have an important, as yet uninvestigated, role in inflammatory bowel disease (IBD) in man. Our project may spark useful medical research in this area. Microbiome profiling will provide information about how diet and the individual animal affect numbers and species of methanogenic archaea in the rumen, thereby aiding research into greenhouse gas emissions from animal agriculture. Ruminal microbial ecology in UK ruminants is under-studied in the modern era: the project will help correct that deficiency.
Veterinary practitioners and public sector advisers from colleges of agriculture and levy bodies will benefit by being better equipped to advise farmers. The project will describe management and nutritional factors associated with variations in the incidence of SARA, information that farmers' advisers can use on-farm. Vets will be able to make better diagnosis of SARA and they will be able to suggest solutions from those feed additives coming out of the SARA project. The probiotic(s) will be useful to help prevent pathological problems in susceptible farms and animals. The adsorbants may be useful in prevention but also to treat the condition. The market potential for a successful feed additive is many millions of pounds. The advisors may consider the remote monitoring system a useful mechanism to monitor the success or otherwise of strategies to ameliorate SARA. The academic partner expert in remote broadband technology has a spin-out SME that will benefit if the technology is found to be generally useful in an on-farm situation. The companies selling these additives and devices will benefit commercially. Initially, those will be from within the consortium. However, as the results are disseminated, more companies in the UK and worldwide will take up the technologies.
Farmers will benefit economically. The beef industry nationwide has a value of £2.22bn at 2009 values. It follows that even a 5% loss of productivity caused by SARA may cost livestock producers £111M p.a. Dairying has a similar incidence of therefore the loss to farmers (and the UK economy) could easily exceed £250M p.a. The economic impact will be felt across the globe in countries that suffer from SARA in their ruminants, including the US (26% of mid-lactation cows suffer SARA), the Netherlands and Germany (18%). Livestock production in the UK will gain against its international competitors and, by retaining the IP in the UK, the economic competitiveness of the United Kingdom will be enhanced. Societal benefit will stem from improved economics and sustainability of food production and a healthier national herd. The livestock will benefit by being less subject to the distress of SARA, thus enhancing animal welfare.