External supporting research Gut barrier & intestinal permeability Peer reviewed EXT-S04

Intestinal Permeability & the Equine Gut Barrier - 2017 Review

A peer-reviewed equine review examining how diet, microbiota, inflammation, exercise, reduced intestinal blood flow and gastrointestinal disease can disrupt the intestinal barrier and increase permeability in horses.

Original study title

Alterations in Intestinal Permeability: The Role of the “Leaky Gut” in Health and Disease

Intestinal permeability Gut barrier Leaky gut Hindgut acidosis Starch Microbiome Short-chain fatty acids Exercise

Study at a glance

Year 2017

Study type Narrative review

Publication Peer-reviewed review article

EquiNectar tested? No

Peer reviewed Yes

Open access No / not specified

Relationship External supporting research

Research question

What did the researchers want to understand?

What is known about normal and altered intestinal permeability in horses, which dietary, microbial, inflammatory, physiological and disease-related factors can disrupt the intestinal barrier, how can permeability be measured, and which potential strategies for supporting barrier function warrant further equine research?

Researchers

Study authors

Amy Stieler Stewart

North Carolina State University

Shannon Pratt-Phillips

North Carolina State University

Liara M. Gonzalez

North Carolina State University

Methodology

How the study was conducted

Study design

This was a peer-reviewed narrative review of published scientific literature.

The authors examined the structure and regulation of the intestinal epithelial barrier, methods used to assess permeability and the major mechanisms capable of increasing intestinal permeability in horses.

Evidence concerning exercise, ischemia, inflammatory bowel disease, infection, microbiota disruption, dietary carbohydrate and hindgut acidosis was reviewed.

The paper also considered potential approaches to supporting barrier function, including short-chain fatty acids, amino acids, nutrients and probiotics, while drawing on research from other species where direct equine evidence was unavailable.

The purpose was to summarize the existing evidence, identify biologically plausible mechanisms and highlight important gaps in equine research rather than calculate a pooled treatment effect.

What was measured

No new animals, biological samples or experimental outcomes were measured in this paper.

The authors reviewed existing research on normal intestinal barrier structure and function, methods for measuring intestinal permeability, causes of barrier dysfunction and potential approaches to supporting intestinal integrity.

The review considered equine evidence alongside relevant findings from humans and other animal species.

Topics included epithelial tight junctions, immune and inflammatory signaling, intestinal blood flow, exercise, gastrointestinal disease, microbiota disruption, dietary starch, hindgut acidosis, short-chain fatty acids and potential nutritional or microbial interventions.

Study findings

Key results

• The intestinal barrier selectively permits nutrient absorption while limiting passage of microorganisms, toxins and other potentially harmful luminal material.

• Increased intestinal permeability can result from inflammatory disease, infection, reduced intestinal blood flow, physical stress and disruption of normal gastrointestinal homeostasis.

• Strenuous exercise can reduce blood flow to the gastrointestinal tract and may contribute to altered intestinal permeability.

• Diet and microbial composition are closely linked to intestinal barrier health in horses.

• Changes in diet, starch source and concentration, antimicrobial use and excessive carbohydrate exposure have all been associated with changes in the equine intestinal microbiota.

• Starch intake beyond preileal digestive capacity can increase the amount of undigested starch reaching the hindgut.

• Increased hindgut starch fermentation can increase organic acid and lactate production, reduce pH and contribute to an acidic intestinal environment.

• Short-chain fatty acids, amino acids, nutrients and microbiome-directed approaches have potential relevance to barrier function, but direct therapeutic evidence in horses remained limited.

• The authors conclude that substantially more equine-specific research into intestinal permeability, its causes and potential interventions is required.

Interpretation

What do the findings mean?

The review presents intestinal barrier integrity as the product of interactions between epithelial cells, tight junctions, immune activity, intestinal blood flow, resident microorganisms and the luminal environment.

Barrier dysfunction can occur when these systems are disturbed by inflammation, infection, ischemia, strenuous exercise, dietary challenge or changes in microbial ecology.

The dietary pathway is particularly relevant to equine hindgut health. The review describes a limit to preileal starch digestion, beyond which undigested starch can enter the large intestine. Increased hindgut starch fermentation can increase acid production and lower pH, potentially damaging the epithelial environment and altering permeability.

The review also highlights short-chain fatty acids, particularly butyrate, as biologically relevant to intestinal epithelial function, while stressing that equine evidence was limited and that responses may depend on concentration and context.

Overall, the paper supports a model in which maintaining a stable digestive and microbial environment is important to preservation of intestinal barrier function. It does not establish that any single nutritional intervention can prevent or correct increased intestinal permeability.

In practice

Why this research matters

The intestinal lining must perform two apparently conflicting roles: allowing nutrients and other useful compounds to be absorbed while preventing inappropriate passage of microorganisms, toxins and other potentially harmful material.

This review shows that intestinal barrier function can be disrupted through several pathways relevant to horses, including gastrointestinal inflammation, altered blood supply, strenuous exercise, infection, changes in the microbiota and dietary disturbance.

Diet is particularly important. When starch intake exceeds the capacity for digestion before the hindgut, more fermentable carbohydrate can reach the large intestine. This can alter microbial fermentation, increase acid production and lower hindgut pH.

The authors also describe the close relationship between microbial composition and intestinal health. Changes in diet, starch concentration, antimicrobial use and excessive carbohydrate exposure have all been associated with changes in the equine intestinal microbiota.

The paper therefore supports viewing gut barrier integrity as part of a wider system involving diet, digestion, fermentation, microbiota, immune activity and intestinal tissue health.

Research transparency

Study limitations

This is a review article and generated no new experimental data.

Although the paper focuses strongly on horses, direct equine research into intestinal permeability and potential nutritional interventions was limited at the time of publication. The authors therefore draw on experimental evidence from several other species including pigs, poultry, rodents, dogs and humans.

The term “leaky gut” describes increased intestinal permeability rather than one single disease or diagnosis. Many different pathological and physiological processes can disrupt barrier function.

Associations between altered microbiota, diet, acidosis, inflammation and permeability do not by themselves establish the direction of causation.

Evidence for potential nutritional approaches, including short-chain fatty acids, amino acids, zinc and probiotics, was particularly limited in horses and sometimes inconsistent.

The authors emphasize that efficacy and safety studies in horses are required before findings from experimental models or other species can be translated into clinical recommendations.

EquiNectar context

How this research relates to EquiNectar

This research did not test EquiNectar and was conducted independently of Tharos Ltd.

Its relevance to EquiNectar is mechanistic. The review describes the intestinal barrier as a dynamic interface influenced by diet, microbial activity, inflammation, exercise, blood flow and gastrointestinal disease.

Of particular relevance, the authors discuss how high starch intake can exceed preileal digestive capacity, allowing undigested starch to reach the hindgut. Rapid fermentation can then increase production of organic acids, reduce pH and disrupt the intestinal environment. The review also discusses evidence linking acidosis with impaired epithelial barrier function.

Published EquiNectar research separately examines changes in fecal pH, microbial populations and fermentation metabolites during supplementation. This review provides independent equine scientific context for why upstream carbohydrate digestion and the downstream hindgut environment may matter to intestinal barrier health.

The paper does not demonstrate that EquiNectar improves intestinal permeability or repairs the gut barrier.

Tharos / EquiNectar involvement

None. This review was conducted independently of Tharos Ltd and EquiNectar. EquiNectar was not evaluated in the paper.

EquiNectar evaluated No

Transparency

Funding & competing interests

Funding statement

PubMed indexes support associated with National Institutes of Health grants K01 OD019911 and T32 OD011130.

Source record

Publication details

Journal

Journal of Equine Veterinary Science

Publisher

Elsevier

Year

2017

Volume

Pages / article

10–22

DOI

10.1016/j.jevs.2017.02.009

PMID

31000910

Species

Horse

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Recommended citation

Stewart AS, Pratt-Phillips S, Gonzalez LM. Alterations in Intestinal Permeability: The Role of the “Leaky Gut” in Health and Disease. Journal of Equine Veterinary Science. 2017;52:10–22. doi:10.1016/j.jevs.2017.02.009.

Intestinal Permeability & the Equine Gut Barrier - 2017 Review

What did the researchers want to understand?

Study authors

Amy Stieler Stewart

Shannon Pratt-Phillips

Liara M. Gonzalez

How the study was conducted

Key results

What do the findings mean?

Why this research matters

Study limitations

How this research relates to EquiNectar

Funding & competing interests

Funding statement

Publication details

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