Despite not understanding the full reasons why acidosis causes laminitis, the profession is aware of several known contributing factors. One of the most important of these is the altered or increased fermentation of rapidly digestible starch, sugar and fructans contained in lush grass. The effect of this increase causes an escalation in lactic acid production, a change in the microbial population and a chronic or acute reduction in the pH of the hindgut that results in acidosis and laminitis.
In chronic cases of acidosis, the gut wall is weakened, allowing for the leakage of toxins and pathogenic bacteria to translocate over the gut wall. This, in turn, creates other health problems in organs far from the gut and triggers a state of low-grade systemic inflammation and lactic acid build-up in muscles.
In chronic cases of acidosis, the gut wall is weakened, allowing for the leakage of toxins and pathogenic bacteria to translocate over the gut wall
Acidosis – a starch overload?
In equids, acidosis is a metabolic state defined by a low pH in the hindgut (Figure 1). It can be caused by the high-starch meals given predominantly to sport/competition horses and is common in Thoroughbred racehorse feeding practices. Though racehorses rarely get full-blown laminitis, acidosis can cause increased digital pulses, sore feet, lethargy, weight loss, loss of appetite, hindgut ulceration and poor performance syndrome.
Acidosis caused by the incomplete digestion of starch derived from grains rather than from lush grass occurs frequently in racehorses (Richards et al., 2006); some grains, such as maize and corn, are digested quicker than others, causing a more rapid increase in lactic acid. Though uncommon outside the Thoroughbred industry, both grains can be found in some sport and showing horse rations. For vulnerable horses, these grains are, therefore, best avoided.
|Symptoms of acidosis from overindulgence of grass and starch ingestion are:|
Decreased or loss of appetite
Cribbing, weaving, anxious pawing of the ground and obvious signs of discomfort
Weight loss and lethargy
Loss of performance – this is sometimes temporary, but acidosis can cause chronic poor performance syndrome
Sore feet and/or increased digital pulses
Severe acidosis – SIRS/SRL
Systemic inflammatory response syndrome (SIRS) or sepsis-related laminitis (SRL) is a type of laminitis caused by gastric inflammation following severe carbohydrate overload and the rapid alteration of the hindgut bacteria community. It often involves a decrease in the less beneficial or commensal butyrate-producing bacteria and a higher percentage of opportunistic pathogens with proinflammatory activity, such as Escherichia, Sutterella and proteobacteria. This is the most extreme type of acidosis, involving multiple symptoms affecting the feet and respiratory system – it can even cause blindness – and the prognosis is guarded.
During SIRS/SRL, the innate immune system (toll-like receptors) is triggered, producing a complex dysregulated proinflammatory response that eventually affects the feet, causing laminitis. The process continues unabated until a counter-response called a compensatory anti-inflammatory response (CAR) is triggered. The timing of this counter-response is vital to the recovery of the horse.
SIRS and its CAR have an equal set of signalling chemicals called cytokines, and many studies indicate that the balance of the response and return to homeostasis is entirely governed by the genetic and immune makeup of the individual and whether the timing of the two processes is in balance with each other (Jacobi, 2002; Xu et al., 2012).
A case study – recognising the clinical signs of severe acidosis
In this case, the mare’s eyes were affected and involved in multiple organ failure as a result of SIRS. The membranes were red and inflamed by day two, and an ulcer appeared in both eyes by day six (Figure 2). Three weeks on, the mare had recovered soundness – the inevitable episode of lameness/laminitis lasted for one week with no rotation of the pedal bone.
Veterinary treatment included flunixin, 24-hour applications of ice to the feet and a four-hourly 160ml syringe of plant antioxidants (as recommended by the vet) mixed with omega-3 oil to mop up, buffer and support the gut wall function and microbial community. Antioxidants were used as they are also known to help diminish and absorb circulating chemicals such as the interleukin (IL) cytokines.
Types of acidosis laminitis and their pathophysiology
1) Starch/grain overload acidosis laminitis
Acidosis laminitis as a result of an overload of starch or grain occurs when undigested carbohydrates are pushed from the small stomach into the hindgut, causing a rapid change in the gut bacteria and a drop in pH. This, in turn, causes the lining of the gut to disintegrate, allowing toxins to be absorbed into the bloodstream, leading to a significant inflammatory reaction.
Acidosis laminitis as a result of an overload of starch or grain occurs when undigested carbohydrates are pushed from the small stomach into the hindgut, causing a rapid change in the gut bacteria and a drop in pH
The time taken for the destruction or separation of the basement membrane is 24 to 40 hours, whereas the time taken for the inflammatory response to appear in the feet (causing more damage) is around 72 hours. During this phase, a chemical linked to the degeneration caused by arthritis is released in the feet.
2) Fructan overload laminitis
This type of acidosis laminitis has an unknown mechanism of action, but the time taken for the destruction/separation of the basement membrane is 24 to 36 hours.
3) Toxaemia laminitis
SIRS (sepsis) laminitis, also known as toxaemia laminitis, is caused by an infection or toxaemia.
While the time taken for the destruction or separation of the basement membrane is 8 to 12 hours, there will also be a rapid loss of shape and arrangement of the sensitive lamellae. For this variant, the response time until a massive inflammatory response in the feet is 90 minutes to 3 hours.
What is the difference between acidosis laminitis and endocrinological laminitis?
Endocrinological (high insulin) laminitis has an unknown mechanism of action; however, it is thought that insulin changes the circulation to the foot, causing vasoconstriction. There is a much slower onset of damage, no separation of the basement membrane and no massive inflammatory response in either the feet or the gut. Instead, lameness is due to the lengthening of the secondary epidermal lamellae as a result of stretching rather than a separation of the basement membrane. Twenty-eight percent of ponies are considered to have a higher-than-normal level of insulin and are said to be predisposed to this type of laminitis (Geor, 2008). The time until the onset of laminitis from abnormally raised insulin levels is 36 to 48 hours.
Mechanical onset laminitis, on the other hand, is caused by uneven weight bearing or concussion. It is distinct from other forms of laminitis until the later stages when there is evidence of secondary inflammation and vascular disruption, which is thought to be caused by inadequate blood flow to the tissues of the foot. Time to onset depends on the loading and level of concussion but is typically within 20 hours.
What is the role of fructans in the onset of acidosis caused by lush spring/autumn grass?
So far, laminitis has not been induced by overfeeding lush/spring grass. Instead, laboratory models use other methods and substances containing a type of fructan; hence, there is a question as to whether fructans trigger laminitis. However, as fructans are digested in the stomach and hindgut, it’s worth taking a closer look at the mechanisms behind gut breakdown.
Research on fructan digestion
At first, researchers thought fructans were indigestible in the stomach and digestion could only occur by bacteria fermentation in the hindgut. However, more recent work has shown that some fructans are broken down in the stomach by acidic hydrolysis or plant enzymes, such as fibractase, alpha galactosidase and chitosan.
Recent work has shown that some fructans are broken down in the stomach by acidic hydrolysis or plant enzymes
Digestion in the stomach starts with the release/secretion of hydrochloric acid (pH 2 to 5) causing the alteration/degradation of protein and the hydrolysis of polysaccharides, including fructans. Fructans are more efficiently broken down at pH 4 (Strauch et al., 2017); however, during a large meal such as the gorging of spring/autumn grass, the pH of the stomach becomes more acidic. This reduces the rate of fructan digestion and degradation, allowing a higher amount of fructans through to the hindgut where their rapid fermentation causes acidosis.
Some researchers identify fructans as the number one cause of the drop in the pH of the hindgut (Crawford et al., 2007), but other studies advocate adding a type of fructan (Jerusalem artichoke inulin) to the diet to improve the digestion of starch and sugars (Bachmann et al., 2021). The latter study indicated that adding a daily dose of fructans in the form of inulin to the diet conditioned the gut bacteria to be more active in the breakdown of inulin fructan to lactic acid and short-chain fatty acids. Priming the gut with a daily small dose of fructan (inulin) will increase the production of n-butyric acid.
Bachmann et al. (2021) reported an increase in the relative abundance of lactic acid-producing Firmicutes and Bacteroides after feeding the horse a fructan supplement.
Horses host Gram-positive bacteria that contain fructokinase, which breaks down fructan and converts it to fructose (Nocek et al., 2011). The conversion of fructan to fructose happens in the ileum, contributing to an increase in permeability of the gut wall (otherwise known as leaky gut syndrome). Recent studies suggest this unusual and unique metabolism of fructose by fructokinase can lead to increased intestinal permeability and inflammation (Johnson et al., 2013), plus the development of insulin resistance because of the effect of fructokinase on liver function.
Previous work by Dougal et al. (2012) has revealed that the predominant bacteria in the ileum (70 percent) belong to the largely Gram-positive family. Furthermore, they discovered that Lactobacillaceae (Gram-positive) account for approximately 16.4 percent of this family.
Impact on metabolism
Fructose triggers a change in metabolism more than any other nutrient, mainly because of its immediate influence on the endocrine system, including leptin, insulin and GLP-1. Therefore, controlling fructose intake and understanding the effect it has is paramount to controlling equine metabolic syndrome (EMS) and laminitis. For some owners who are constantly managing their horse’s diet to reduce/minimise or remove fructose altogether, understanding the conversion of fructan to fructose by the gut bacteria might be the missing piece of the jigsaw.
Clearly, the horse is designed to break down and use fructans in a beneficial way. However, the regulatory/processing systems that exist may have been overwhelmed by the high levels of fructans arriving in the digestive system in grass consumed by horses turned out on lush pastures.
Do histamines play a role in the onset of acidosis?
As the pH of the gut drops and pathogenic and lactic acid-producing bacteria increase, some of the bacteria produce lectins (Cohen et al., 2022). An abnormal increase in lectin increases the discharge of histamine from gastric mast cells and histamine-producing bacteria (Allisonella histaminiformans) that use histamine to reproduce – these thrive in the acidic environment. These bacteria have been identified in the faeces of cattle and caecum of horses fed grain and grass but not from horses fed hay.
As a powerful inflammatory chemical that can cause the sudden inflammation of the gut wall and the dilation of blood vessels, histamine can also trigger the onset of laminitis
Histamine production is part of an allergic reaction to, for example, foods containing high levels of lectin (grains). The allergic reaction to the lectin causes the gut wall to release even more histamine. As a powerful inflammatory chemical that can cause the sudden inflammation of the gut wall and the dilation of blood vessels, histamine can also trigger the onset of laminitis either directly or because of a vasodilatory event.
Are there any technological advances in the analysis of acidosis?
Current methods of testing for acidosis include a kit to test the pH of faeces. Though quick, this method cannot detect abnormal bacteria profile patterns that could help restore and rebalance the biome. EquiBiome Analysis, on the other hand, provides a real-time snapshot of the microbial community (Figure 3), making it the most accurate test available. It is able to detect microbial profile patterns and can distinguish between dysbiosis (imbalances) of horses with endocrinopathic laminitis, EMS and acidosis.
There are plans to develop a mobile biosensor that continuously detects the abnormal bacteria community patterns initially identified by the EquiBiome analysis (Figure 4). The lactic acid biosensor would continue to help to monitor the health of the microbiome and management but via the gut instead. This is useful because not all horses respond in the same way (see Figure 3) and would allow those who are more vulnerable to benefit from closer monitoring.