The link between the gut and the foot:
a summary of some of the work currently being undertaken by the laminitis research group at the Royal Veterinary College, London.

Simon Bailey BVMS, PhD, MRCVS

Laminitis (founder) is one of the most important conditions affecting the United Kingdom horse population in terms of prevalence, the serious nature of the condition for the individual animal and the cost of treatment. From a study involving 113 000 horses in the UK (Hinckley and Henderson, 1996), it was estimated that the total prevalence of acute laminitis in the UK was over 8,000 cases annually, giving a prevalence of 7.1%. The majority of affected animals are ponies (Dorn et al, 1975), particularly those at grass, with a greater prevalence during times of high grass growth; this seasonal occurrence has been recognised in studies of populations both in the UK and USA (Hinckley and Henderson, 1996; Dorn et al, 1975). In a recent study of a large charity farm in East Anglia with a population of 1140 horses and ponies, there were an average of 148 episodes of laminitis (prevalence of 13%) occurring each year (between 1997 and 1999) involving 113 animals (Katz et al., 2000).

The clinical signs of laminitis represent the end result of a systemic condition which has many predisposing factors such as grain overload, lush pasture and colic, leading to a common pathogenic pathway (Hood et al, 1993). The haemodynamic theory of the pathogenesis of acute laminitis suggests that vasoconstriction within the digital circulation causes a decreased perfusion to the nutrient laminar capillaries, leading to ischaemia, followed by painful reperfusion injury and enzyme activation (Hood et al, 1993; Johnson et al, 1998). This damage may rapidly lead to tearing of the laminar bonds and displacement of the pedal bone away from the hoof wall.

A second theory has been proposed to explain the pathophysiology of acute laminitis, the connective tissue theory. This proposes that degeneration of the connective tissue of the basement membrane (Pollitt & Daradka, 1998) mediated by activation of matrix metalloproteases (MMPs) (Johnson et al., 1998; Pollitt et al., 1998) is a primary event in acute laminitis. These two theories are not mutually exclusive. Marked activation of three isoforms of MMPs has been reported to occur in models of myocardial infarction (Carlyle et al., 1997). It is possible, therefore, that ischaemia followed by reperfusion could lead to activation of MMPs within the digit.

The trigger factor(s) linking the gastrointestinal tract disturbances with the onset of laminitis are not known precisely. It is known, however, that excess carbohydrate, reaching the caecum/large intestine, either in the form of starch from grain or water-soluble fructans from the pasture, can result in fermentation involving gram positive bacteria with production of lactic acid and other metabolites. It was previously thought that endotoxin, released from Gram negative bacteria, was the cause of laminitis; however endotoxin on its own will not cause laminitis (Hood, 1995), therefore other potential trigger factors are being investigated.

When fermentation processes are undertaken in natural production of food products, such as cheese, beer or wine, the micro-organisms involved generate amines as a by-product of the fermentative processes, through the oxidative decarboxylation of amino acids. Fermentation in the intestinal tract of herbivores in general, and ruminants in particular, leads to the formation under certain circumstances of monoamines including tyramine (Van der Horst 1961; Dain et al., 1955) isoamylamine, phenylethylamine and isobutylamine (Fraser & Butler 1964). Many of these amines are vasoactive either directly or because they inhibit the uptake and metabolism or stimulate the release of naturally occurring vasoactive substances such as noradrenaline or serotonin (5-hydroxytryptamine).

We now have direct evidence that these amines are found in high concentrations in the caecum of the horse, particularly those on lush spring/summer grass (Bailey et al., 2000) and are also detectable in much lower concentrations in the plasma of healthy horses and ponies (unpublished observations). Increased production of isoamylamine and phenylethylamine occur when caecal cultures are fed excess carbohydrate (Bailey et al., 2001). In addition, caecal mucosal permeability has been shown to increase dramatically when the pH drop associated with fermentation occurs (Weiss et al., 2000), suggesting that these amines will have free access to the systemic circulation under these circumstances. The amines released from the caecum may cause vasospasm in the digit, both directly and by raising plasma serotonin concentrations (by inhibiting its uptake into endothelial cells stimulating its release from platelets). Therefore these compounds could trigger vascular changes in the foot leading to acute laminitis. Further work is ongoing to study the effects of these compounds, and to gain a better understanding of the factors controlling blood flow in the highly specialised circulation of the horse's foot. It is hoped that these studies will lead to novel strategies for preventing this painful and common condition.


Bailey S.R., Elliott J. (1998)
5-hydroxytryptamine in equine plasma constricts digital blood vessels in vitro: implications for the pathogenesis of acute laminitis
Equine Veterinary Journal 30, 124-130.

Bailey, S.R., Rycroft, A., Marr, C.M., Elliott, J. (2000) Identification and quantification of amines in equine caecal liquor. Proceedings of the 39th British Equine Veterinary Association Congress, p206-207

Bailey, S.R., Rycroft, A., Marr, C.M., Elliott, J. (2001) Effect of carbohydrate oerload on production of vasoactive amines in equine caecal contents in vitro. Proceedings of the 40th British Equine Veterinary Association Congress, p213

Carlyle, WC, Jacobson, AW, Judd, DL, et al., (1997)
Delayed reperfusion alters matrix metalloprotease activity and fibronectin mRNA expression in the infarct zone of the ligated rat heart.
Journal of Molecular and Cellular Cardiology., 29, 2451-2463.

Dain, J.A., Neal, A.L., Dougherty. R.W. (1955)
The occurrence of histamine and tyramine in rumen ingesta of experimentally overfed sheep.
Journal of Animal Science, 14, 930-935.

Dorn C.R., Garner H.E., Coffman J.R., Hahn A.W., Tritschler L.G. (1975)
Castration and other factors affecting the risk of equine laminitis
Cornell Veterinary Journal 65, 57-64

Fraser J.G, Butler, G.W. (1964)
Steam-volatile amines in rumen liquor from cattle and sheep.
New Zealand Journal of Agricultural Research, 7, 707-712.

Ghenghesh, K.S., Drucker, D.B. (1989)
Gas liquid chromatography of amines produced by the enterobacteriacae.
Brazilian Journal of Medical Biological Research, 22, 653-665.

Hinckley K.A., Henderson I.W. (1996)
The epidemiology of equine laminitis in the UK
Proceedings of the 35th congress of the British Equine Veterinary Association, Warwick. pp62.

Hood D.M., Grosenbaugh D.A., Mostafa M.B., Morgan S.J., Thomas B.C. (1993)
The role of vascular mechanisms in the development of acute equine laminitis
Journal of Veterinary Internal Medicine 7, 228-233

Hood, D.M. 1995. Endotoxaemia as a direct cause of laminitis. In: Proceedings of the American Assiociation of Equine Practitioners, 41: 245-247.

Johnson P.J., Tyagi S.C., Katwa L.C., Ganjam V.K., Moore L.A., Kreeger J.M. (1998)
Activation of extracellular matrix metalloproteinases in equine laminitis
The Veterinary Record 142, 392-396

Pollitt, CC & Daradka, M (1998)
Equine laminitis basement membrane pathology: loss of type IV, type VII collagen and laminin immunostaining.
Equine Veterinary Journal, Suppl. 26, 139-144.

Pollitt, CC, Pass, MA, Pollitt, S. (1998)
Batimastat (BB-94) inhibits matrix metalloproteases of equine laminitis.
Equine Veterinary Journal, Suppl. 26, 119-124.

Tavakkol A & Drucker D.B. (1984)
Qualitative gas chromatographic analysis of bacterial amines as their acetylated derivatives.
Journal of Chromatographic Science, 274, 37-44.

Van der Horst, C.J.G. (1961)
Keto-acids and amines in rumen liquid of cattle.
Nature (Lond), 191, 73-74.