Laminitis and the microbiome- what are the links?

Introduction and Basic Understanding

Laminitis affects hoofed animals, primarily manifesting as inflammation in the lamellae that can lead to failure of the support system for the distal phalanx (coffin bone). While horses are the most studied species, this condition also impacts donkeys, goats, and cattle. The development of laminitis involves multiple factors, with both inflammatory and non-inflammatory pathways playing crucial roles.

Metabolic and Endocrine Factors

Recent research has highlighted insulin dysregulation as a key driver, particularly in cases stemming from pituitary pars intermedia dysfunction or equine metabolic syndrome. According to Knowles et al (2023), measuring insulin levels - either in an unfasted state or an hour after corn syrup administration - can predict endocrinopathic laminitis (EL). The mechanism may involve insulin's effects on IGF-1R in lamellar tissues, as suggested by Grenager (2021). Additional pathways include the formation of toxic methylglyoxal through disrupted carbohydrate metabolism (Vercelli et al 2021), along with alterations in how the body processes glycerophospholipids and glucose (Delarocque et al 2021).

Dietary Influences and Gut Health

Diet plays a significant role in triggering inflammatory responses. Particularly concerning is grazing on new pasture grass, which is known to increase laminitis risk in horses. Water-soluble carbohydrates (WSCs), especially oligofructans (OF), are abundant in cool-season pasture grasses like perennial ryegrass and tall fescue (Kramer et al 2020). These WSC levels peak during cooler weather (Kagan, 2022), correlating with increased laminitis cases.

The digestive system struggles to process high levels of OFs and starch in the small intestine, leading to increased bacterial fermentation in the hindgut. Studies have shown that horses with laminitis typically show higher levels of Lactobacillus, Streptococcus, and Enterobacteriaceae (Ayoub et al 2022; Garber et al 2020). Bustamante et al (2022) found that horses on high-starch diets experienced a dramatic increase in Lactobacillus (from 0.1% to 7.4%) while beneficial Ruminococcaceae decreased (from 11.7% to 4.2%), accompanied by abdominal pain and lameness.

Inflammatory Cascade and Systemic Effects

The shift toward lactic acid-producing bacteria, combined with a decrease in bacteria that utilize lactic acid, creates an acidic gut environment. This triggers metabolic inflammation, leading to endotoxin (lipopolysaccharide, LPS) production and increased gut wall permeability. Research by Tuniyazi et al (2021) demonstrated that OF administration led to laminitis characterized by lower fecal pH, elevated lactic acid, and increased blood LPS levels. Similar patterns emerged in studies of cattle (Guo et al 2021) and goats (Zhang et al 2018) on high-starch diets.

LPS further complicates the condition by inducing insulin resistance (Lebrun et al 2022; Perng et al 2022) and disrupting glucose and phospholipid metabolism (Javaid et al 2022). It also promotes the growth of lactate-producing bacteria (Dai et al 2020), creating a self-perpetuating cycle. Recent research by Lin et al (2022) suggests that lactate in fat cells may link gut metabolism to systemic inflammation and insulin resistance, with complex mechanisms detailed by Fujisaka et al (2023).

Additional Risk Factors and Treatment Approaches

Laminitis can also develop following systemic infections, particularly in cases of colitis, diarrhea, pneumonia, or intestinal injury that trigger widespread inflammation (Garber et al 2020). Treatment typically involves managing local inflammation and immune cell responses, with cold therapy and anti-inflammatory medications serving as important supportive measures (Leise and Fugler 2021).

Given the strong connection between gut bacteria, metabolic issues, and laminitis, researchers suggest that modifying the microbiome could be an effective therapeutic strategy (Chaucheyras-Durand et al 2022; Garber et al 2020). This approach might even help prevent various inflammatory conditions through dietary supplementation.

References

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