Laminitis is one of the most serious diseases of the equine foot accounting for 15% of all lameness in the USA, and 10% of horses in the UK, with 4.7% euthanised as they are unable to recover from the devastating injury to the feet.
Laminitis is a common, complex disease, causing a great deal of pain and disability to horses. The two most common types of laminitis originate from
a) An underlying metabolic dysregulation such as Equine Metabolic Syndrome or pituitary pars intermedia dysfunction (PPID, or equine Cushing’s disease.
b) The disruption of the hindgut through the overconsumption of fructans or starch.
c) Other contributing factors include medical interventions, injury, obesity, pregnancy, infectious disease, sepsis, and trauma.
The Role of the Microbiome in Laminitis
Horses with EMS/laminitis have a different microbiome profile to those horses with laminitis caused by the ingestion of starch/fructans. For more info on the microbiome relating to EMS.
Laminitis caused by a gastric disturbance is thought to be from the overconsumption of starch (cereal or grass) and fructans (grass). Undigested food overflows from the small intestine into the hindgut where it causes a rapid change/ disruption to the bacteria community and an increase in the production of lactic acid.
During this event, there is evidence to show an increase in the percentages of Lactobacillus and Streptococcus and an increase in potential pathogens Veillonella and serratia (Tuniyazi et al 2021). There is also some evidence to suggest that an increase in Streptococcus bovis/equinus complex may be associated with the onset of laminitis in the horse without an increase of starch/fructans.
At the same time, there is a decrease in species richness and evenness (diversity) with a clear separation between healthy horses and those with laminitis, largely identified through the increase in lactobacillus.
Lactobacillus produces lactic acid, as levels rise there is a corresponding increase in bacteria that utilise lactic acid (Megasphaere) and a decrease in bacteria that are unable to survive in an acidic environment ie. Fibrobacter, Phascolarctobacterium, Papillibacter, and Alloprevotella, the reduction of core members of the microbiome cause discomfort, instability, and gastric sensitivity.
Fructans
Though fructan as a contributing factor to laminitis has recently gone out of fashion, Johnson et al 2013, present an interesting theory of why and how gut bacteria might play a part in increasing the amount of fructose (leading to acidosis) produced by horses through the conversion of fructan.
Theory of mechanism is as follows…
Fructose is a simple sugar found in grass, but fructose also exists as a polymer (fructans are fructoses joined together) mammals can’t digest the fructans but gram-positive bacteria have been discovered in the gut that produce fructanases, these can break down the fructan and convert it to fructose. Furthermore, the paper proposed that the production or conversion of the fructan to fructose happened in the ileum (part of the small intestine) causing an increase in permeability of the gut wall otherwise known as leaky gut syndrome.
Recent studies suggest that this unusual and unique metabolism of fructose by gut bacteria generated fructanases can lead to increased intestinal permeability and inflammation.
The top fructanase producing bacteria are, Streptococcus salivarus, Strep. mutans, all species of Bacillus, Clostridia, Bifidobacterium and Bacteroides fragilis.
Lactic Acid
Any lactic acid not utilised in the gut by the Megasphaere finds its way into the bloodstream evidence suggesting that blood lactate might be an important contributor to the onset of laminitis.
Other metabolic increases in the serum of affected horses include LPS, the cell wall component of gram-negative bacteria. LPS has been previously associated with the onset of starch overload laminitis, through the killing off of non-acid-loving gram negative bacteria (Fibrobacter, Phascolarctobacterium, Alloprevotella). Tuniyazi et al. (2021) measured a significant increase in LPS in the serum of affected horses together with similar significant increases in lactic acid and histamine. See diags below.
Rebalancing the gut bacteria- Pack of Polyphenols
A polyphenol is a plant chemical found in the outer layers of the leaves and stems of most plants. They can also be aromatic, found in the flowers and the fruits/seeds of wild plants. There are over 8,000 different polyphenols, some are easily absorbed through the equine G.I. tract (flavonoids) and some remain in the gut, where they modulate the gut bacteria within the fermentation vat called the cecum.
Polyphenols are known to protect against oxidative stress and the increase of AGE (Advanced glycation end products) which rise 48 hours prior to a laminitis attack.
Giving bute/danilon to horses with laminitis is the most obvious course of action and also the quickest and safest way to ease the pain but unfortunately, this popular and commonly used drug has no effect on the high levels of circulating inflammatory chemicals. The inflammatory chemicals are responsible for damage done to the sensitive laminae, which peak at 20-48hrs after the onset of lameness. Whilst bute makes the horse and owner feel better, there is sadly no resolution to the damage continuing unabated in feet.
The affected horse will benefit from extra doses of antioxidants to minimise and mop up the effects of the circulating inflammatory chemicals that bute is unable to change or effect, the symptoms of which are Obel grade 1 laminitis (paddling or lifting one foot then the other, short, stilted gait in trot).
Horses with the starch/fructan overload type of laminitis will have raised levels of IL-1 IL-1β, IL-6, IL-12p35, COX-2, E-selectin and ICAM-1 and whilst the bute will mask the pain it does not alter the cocktail of deadly chemicals the laminitis episode has released, these chemicals rapidly causing devastating levels of breakdown.
A cocktail of the strongest plant anti-inflammatories are required to dampen down, buffer and reduce the effects of all the chemicals released, usually found in the bark or more woody part of the plant/shrub/ including, uncario tomentosa, smilax and maytenus ilicifolia.
The Equibiome Pack of Polyphenols contains not only unabsorbed polyphenols that modulate the gut bacteria but also flavonoids with anti-inflammatory actions, this may be the easiest way to add an extra dose to the diet, if the horse isn't eating then mix 20 mls of omega 3 rich oil (linseed or flax)and syringed in three times per day.
Polyphenols and the gut bacteria
Polyphenols can be used to improve gut health due to their already-established health benefits and strong antioxidant potential. Polyphenols have antimicrobial activity able to reduce the bad (pathogenic) gut bacteria whilst feeding the good gut bacteria which then generates more beneficial active metabolites, which can modulate the composition of the equine gut microbial community.
In vivo studies have demonstrated that these polyphenols are transformed by bacteria which thrive when provided with phenolic compounds. One important member of the microbiome of horses is Akkermansia muciniphila, called the antiobesity bacterium, which increases to supplementation with polyphenols, 90% of all horses tested have very low levels of this important health-supporting bacteria.
Polyphenols have broad antimicrobial actions reducing the bad bacteria and allowing for a bloom of beneficial gut bacteria.
The term for this dual-action prebiotic is duplibiotic, a term used to describe an active plant compound that remains in the gut in an unabsorbed state and modulates the microbial community by both antimicrobial and prebiotic modes of action. The duplibiotic effect is a natural therapeutic helping to reduce gut imbalances and avoid metabolic distrubances.
Conclusions
Laminitis caused by starch/fructan overload causes detrimental changes to the microbiome.
The microbiome may remain sensitive to another event (high levels of pathogenic bacteria and over-representation of lactate-producing bacteria).
There is an increase in lactate-producing bacteria, other bacteria chemicals (LPS) and histamine, which makes it's way into the bloodstream of the horse that may be responsible for the damage caused in the structures of the hoof.
Horses with EMS/endocrinopathic laminitis have a different microbial profile.
Polyphenol compounds found in medicinal plants have a duplibiotic effect on the biome helping to restore balance between the good and bad bacteria.
References
Edwards, J. E., Shetty, S. A., Van Den Berg, P., Burden, F., Van Doorn, D. A., Pellikaan, W. F., ... & Smidt, H. (2020). Multi-kingdom characterization of the core equine fecal microbiota based on multiple equine (sub) species. Animal Microbiome, 2(1), 1-16.
Tuniyazi, M., He, J., Guo, J., Li, S., Zhang, N., Hu, X., & Fu, Y. (2021). Changes of microbial and metabolome of the equine hindgut during oligofructose-induced laminitis. BMC veterinary research, 17(1), 1-13.
Chaucheyras-Durand, F., Sacy, A., Karges, K., & Apper, E. (2022). Gastro-Intestinal Microbiota in Equines and Its Role in Health and Disease: The Black Box Opens. Microorganisms, 10(12), 2517.
Weinert-Nelson, J. R., Biddle, A. S., Sampath, H., & Williams, C. A. (2023). Fecal Microbiota, Forage Nutrients, and Metabolic Responses of Horses Grazing Warm-and Cool-Season Grass Pastures. Animals, 13(5), 790.
Ayoub, C., Arroyo, L. G., MacNicol, J. L., Renaud, D., Weese, J. S., & Gomez, D. E. (2022). Fecal microbiota of horses with colitis and its association with laminitis and survival during hospitalization. Journal of Veterinary Internal Medicine, 36(6), 2213-2223.
Rodríguez-Daza, M. C., Pulido-Mateos, E. C., Lupien-Meilleur, J., Guyonnet, D., Desjardins, Y., & Roy, D. (2021). Polyphenol-mediated gut microbiota modulation: Toward prebiotics and further. Frontiers in Nutrition, 8, 689456.